M.H. Gault

Prediction of creatinine clearance from serum creatinine.

A formula has been developed to predict creatinine clearance (Ccr) from serum creatinine (Scr) in adult males: Ccr = (140 – age) (wt kg)/72 × Scr(mg/100ml) (15% less iA formula has been developed to predict creatinine clearance (Ccr) from serum creatinine (Scr) in adult males: (see article)(15% less in females). Derivation included the relationship found between age and 24-hour creatinine excretion/kg in 249 patients aged 18-92. Values for Ccr were predicted by this formula and four other methods and the results compared with the means of two 24-hour Ccrs measured in 236 patients. The above formula gave a correlation coefficient between predicted and mean measured Ccrs of 0.83; on average, the difference predicted and mean measured values was no greater than that between paired clearances. Factors for age and body weight must be included for reasonable prediction.

Clinical features and severity of nonspecific symptoms in dialysis patients

Nonspecific symptoms are common in dialysis patients but few methods are available to measure their severity and their response to alteration in dialysis therapy. To determine the clinical features and measure the severity of the most important symptoms in end-stage renal disease (ESRD) patients, 97 dialysis patients were interviewed, 63 of whom were reinterviewed 1 year later. For comparison 82 transplant recipients were also interviewed. The six most important symptoms in dialysis patients (using the product of the patients perception of severity and prevalence) were tiredness, cramps, pruritus, dyspnea, headaches and joint pain. The symptoms were long-standing, occurred frequently, with little difference in prevalence between hemo- and peritoneal dialysis patients, and were often unrelated to a hemodialysis session. For each symptom, several dimensions of severity were assessed including frequency, duration, effect on sleep, daily living, activity, subjective quality of life and necessity for drug therapy. Often these dimensions did not correlate with patients perception of severity. For each symptom these items were combined to give an aggregate score with a range 0-10. Interobserver reproducibility for each symptom score was greater than or equal to 0.7 but intraobserver reproducibility was poor for 3 symptoms, because of the fluctuating nature of the symptoms. Construct validity was demonstrated by finding a significantly worse distribution of aggregate scores for tiredness, cramps, pruritus, dyspnea and nausea/vomiting in dialysis compared to transplant patients. Aggregate scores changed little after 1 years follow-up in stable dialysis patients but significant improvement in the aggregate scores for tiredness, dyspnea and nausea/vomiting were observed in 14 patients after successful transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Hemodialysis Intravascular Hemolysis and Kinked Blood Lines

Between May 29 and September 13, 1991, 4 patients developed acute intravascular hemolysis during hemodialysis with Monitral-S delivery systems and Hospal BSM A77 blood lines. All had malaise, nausea and headache; 3 had severe abdominal pain and 2 became very ill. Plasma hemoglobins were 3-21 g/l and LDH 542-3,300 IU in the 4 patients. Hepatoglobin became unmeasurable in 3 and was 0.09 g/l in the 4th patient. Soon afterwards, we found the arterial blood line tightly kinked at the dialyzer inlet port in the 4th patient and released it; he developed abdominal pain, hemolysis was present. We then found these lines had an extra long pump segment, and the rest was short and fitted poorly. When put in the first tubing organizer, severe kinking could occur just after the pump segment, causing back pressure but no alarm. We produced early visible hemolysis in a 1-liter circulating closed loop blood system with the blood line kinked either at the dialyzer inlet or just below the first arterial line tubing organizer with 40 g/l free plasma hemoglobin by 30 min. We excluded reported causes of intravascular hemolysis during hemodialysis. No hemolysis occurred before or during the 9 months after we discarded BSM A77 lines. The evidence indicates that kinked blood lines caused the hemolysis.

HEMODIALYSIS WITH A PERMCATH KEPT OPEN WITH STREPTOKINASE AND LATER CITRATE IN A HEPARIN-SENSITIVE PATIENT

M.H. Gault, Division of Nephrology, The General Hospital, Health Sciences Centre, St. John’s, Nfld. A1B 3 V6 (Canada) Dear Sir, A 74-year-old 56 kg blind woman developed dialysis-depended acute on chronic renal failure following coronary angiography in February 1989. She had gross lymphe-dema of the left arm following radical mastectomy 5 years before and multiple-thrombosed vessels in the right arm. She was considered unsuitable for standard arteri-ovenous graft or fistula, or for continuous ambulatory peritoneal dialysis. Soon after dialysis was started with a subclavian catheter using heparin in the catheter between dialyses and for anticoagulation during dialysis, her platelet count fell to 20,000 and she developed deep-vein thrombosis in her left leg. Platelets returned quickly to normal when all heparin was discontinued. Warfarin therapy was commenced and prothrombin time was kept on average 15% of control. A test for platelet heparin sensitivity was positive [1]. A Permcath (Quinton Instrument Co., Seattle, Wash.) was introduced through the right internal jugular vein into the superior vena cava. Starting March 15, patency was maintained between dialyses with 20,000 units streptokinase (Hoechst, Montreal, Que.) in a volume of 1.5 iVsaline in both arterial and venous compartments. For 9 months, dialysis for 4 h was performed twice weekly with saline flushes as needed, but without an anticoagulant other than warfarin. There was no clotting of the catheter and rarely clotting of the dialyzers. Blood flow was estimated at 275–400 ml/min during dialysis. The dialyzer was a Filtral 16 and the delivery system a Monitrol S, both from Hospal Ltd., Montreal, Que. Dialyzer reuse averaged 3.5 times. Activated clotting times (HemoTek Inc., Englewood, Colo.) remained at 100–110 s at the start of dialysis. Hemoglobin was maintained > 80 g/l by transfusion when needed. On November 6th, treatment of a bacteremia due to infection related to the Permcath with Staphylococcus epidermidis was commenced with vancomycin and later with rifampin 600 mg daily. The latter drug induced a fall in the prothrombin time and then there was recurrent clotting of the Permcath and dialyzers. Predialysis values for activated clotting times fell to 60–70 s and prothrombin time to 110% of control. On January 4, 1990, the old catheter was removed and a new Permcath was inserted on the right into the atrium over a guide wire, but in a new tunnel, and an arteriovenous fistula was fashioned in the right arm. It was not considered possible to insert a graft without heparin. Then rifampin was discontinued. The large amount of streptokinase infused around that time (1 million units) probably led to the worsening anaphylactoid reactions which were associated with hypotension, erythema, edema and a hot sensation

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.

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.

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.

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.

Heparin, Fatty Acids and Sodium, Potassium-ATPase Inhibition by Plasma Factors during Hemodialysis

To assess the relationship between heparin and the associated increase in nonesterified fatty acids (NEFA) and their possible influence on Na,K-ATPase during hemodialysis, we studied two groups of patients: (1) 12 patients on chronic hemodialysis dialysed with heparin and (2) 6 patients dialysed without heparin. All 12 patients who received heparin anticoagulation had a 7-fold rise in NEFA on average and also had an increase in circulating inhibitors of Na,K-ATPase assayed by 3H-ouabain displacement from Na,K-ATPase and/or by effect of plasma on the uptake of 86Rb by rat aortic rings. Serial assays in 3 of the patients receiving heparin showed NEFA and inhibitory changes to be at or near maximum within 30-60 min. Of the individual NEFA, the greatest relative increases were in oleic (18:1) and linoleic (18:2) acids, and the strongest correlations were between linoleic acid and both 3H-ouabain displacement (r = 0.94) and 86Rb uptake (r = 0.86). However, a small and slower increase in NEFA also occurred in 3 of the patients dialysed without heparin. We conclude that heparin anticoagulation during dialysis leads to a rapid and marked increase in circulating NEFA, particularly the unsaturated fatty acids, with a corresponding interference with Na,K-ATPase activity. The clinical significance of these findings is unknown. The rise in NEFA during dialysis without heparin in some patients suggests that factors other than heparin may also contribute to the rise in NEFA.