L. Arisz

Creatinine clearance during cimetidine administration for measurement of glomerular filtration rate

Creatinine clearance inaccurately estimates true glomerular filtration rate (GFR) because of tubular secretion of creatinine. We studied the ability of oral cimetidine, a blocker of tubular creatinine secretion, to improve the accuracy of measuring creatinine clearance. Clearances of inulin and endogenous creatinine were simultaneously measured in 16 patients with renal disease before administration of cimetidine and during 8 successive 3 h clearance periods with cimetidine 400 mg as priming dose followed by 200 mg every 3 h. At baseline, creatinine relative to inulin clearance (ClC/Cll) ranged from 1.14 to 2.27. With cimetidine, ClC/Cll approached unity in 8 patients (mean 1.02 [SD 0.03]), but considerably exceeded unity in 8 others (1.33 [0.14]). Plasma cimetidine/creatinine ratio was smaller in this second group, due to significantly higher renal clearance of cimetidine (333 [136] vs 165 [89] ml/min, p = 0.01). In a further study, cimetidine dose and, consequently plasma cimetidine concentration, was increased in 6 additional patients who had incomplete inhibited previously. This increased dose completely inhibited tubular creatinine secretion in the third until the sixth hour, so that creatinine clearance equalled GFR. Provided an adequate dose of cimetidine is given, 24 h creatinine clearance during administration of drug measures GFR accurately in patients with renal disease. However, because of the maximum daily dose of cimetidine that is advised, short clearance times (3 h) are recommended.

Peritoneal Permeability to Proteins in Diabetic and Non-Diabetic Continuous Ambulatory Peritoneal Dialysis Patients

Peritoneal permeability to proteins was measured in diabetic and non-diabetic continuous ambulatory peritoneal dialysis patients during peritonitis and control periods. Clearances of albumin, transferrin, IgG, C3 and alpha 2-macroglobulin appeared to decrease as molecular weight increased. This relationship could be described by a power curve fit. The decrease was more than could be explained by differences in free diffusion only, indicating a size-selective barrier in the peritoneum. For all measured proteins clearances were higher in the diabetic patients. This may reflect a generally increased permeability due to their microangiopathy. The largest increase in protein loss and protein clearances was found during peritonitis. Our results do not suggest increased local production of any of the investigated proteins during the inflammation. Therefore, an increase in either peritoneal permeability or effective surface area or both is the most likely explanation. It is concluded in this study that peritoneal protein clearances are dependent on their molecular weight and that they are proportionally increased in patients with diabetes and during peritonitis.

Cardiac and hemodynamic effects of hemodialysis and ultrafiltration

Imbalance between cardiac oxygen supply and demand may trigger cardiac events in already vulnerable hemodialysis (HD) patients. We studied the effect of ultrafiltration (UF) and HD in nine chronic HD patients by continuously measuring blood volume (BV; by Critline), blood pressure (BP; by Portapres), and changes in hemodynamics (Modelflow) during isolated UF (iUF) of 500 mL in 30 minutes and subsequent HD combined with UF (HD + UF). Aortic pressure was reconstructed from finger pressure. Changes in cardiac oxygen supply were assessed by calculating the area under the aortic pressure curve during diastole (diastolic pressure time index [DPTI]). Changes in cardiac oxygen demand were assessed by calculating systolic pressure time index (SPTI). BV decreased 4.0% +/- 1.8% during UF and 7.3% +/- 3.3% during HD + UF (both P < 0.01). Systolic BP did not change; diastolic and mean BP increased 11 +/- 7.4 and 11 +/- 8.4 mm Hg during iUF, respectively (both P < 0.01), and stabilized during HD + UF. Overall pulse pressure decreased 19 +/- 11.1 mm Hg (P < 0.01). Heart rate increased 13 +/- 11 beats/min (P < 0.01) and systemic vascular resistance increased 59% +/- 51% (P < 0. 01), whereas stroke volume and cardiac output (CO) decreased by 40% +/- 17% and 30% +/- 13%, respectively (both P < 0.01). Both cardiac oxygen supply (DPTI) and demand (SPTI) increased during iUF, and both decreased during HD + UF. By the end of the procedure, DPTI/SPTI ratio had increased 9% +/- 8% (P < 0.05). Changes in CO correlated closely to changes in BV. Despite large changes in hemodynamics during uncomplicated UF and HD, the balance between cardiac oxygen supply and demand (DPTI/SPTI ratio) did not decrease, but improved slightly.

Simple Assessment of the Efficacy of Peritoneal Transport in Continuous Ambulatory Peritoneal Dialysis Patients

The efficacy of peritoneal transport was assessed in 13 permeability studies in 11 continuous ambulatory peritoneal dialysis (CAPD) patients. During each study the in situ intraperitoneal volume was measured as well as the dialysate and plasma concentrations of various solutes with a molecular weight range from 60 to 5,500. As clearance estimations are unsuitable for the purpose of permeability studies, mass transfer area coefficients were used. By applying a simple mathematical model assuming first-order kinetics, these coefficients were calculated for urea, lactate, creatinine, glucose, kanamycin, and inulin. The accuracy of the calculations is indicated by their r values. After pooling these correlation coefficients, the mean approached 1.00 for all solutes with high confidence limits, indicating the usefulness of the model. A further simplification was tested using only an initial- and end-dialysate sample and two blood samples, without the measurement of the in situ intraperitoneal volume. Except for inulin the results of this simplification correlated well with the results described above. The reproducibility of the simplified mass transfer area coefficient calculations was investigated on 15 occasions in 3 other CAPD patients. The coefficients of variation of low molecular weight solutes varied between 15 and 20%. It is concluded that mass transfer area coefficient estimations using the latter method can be performed in any CAPD patient and probably yield sufficient information to establish the efficacy of the membrane transport mechanism during clinical follow-up.

The Time Course of Peritoneal Transport Kinetics in Continuous Ambulatory Peritoneal Dialysis Patients Who Develop Sclerosing Peritonitis

The time course of measurements of peritoneal solute transport in four continuous ambulatory peritoneal dialysis (CAPD) patients who developed sclerosing peritonitis is described. Loss of fluid removal capacity was found in all of them. In three, this loss was associated with an increase in peritoneal absorption of glucose from the dialysate and an increase in the transperitoneal transport rates of low-molecular-weight solutes and proteins. In the other patient a decrease in all these parameters was found. This seems to imply that the effective peritoneal surface area was increased in three patients and decreased in one. Peritoneal permeability to macromolecules remained unchanged as judged by the ratio between the clearance of IgG and albumin. Among the possible factors that contribute to the development of sclerosing peritonitis, some are likely to lead to a larger effective peritoneal surface area, like prostacyclin and the formation of new capillaries in poorly vascularized parts of the peritoneum. Others, such as extensive formation of collagen, could lead to a smaller effective surface area. Individual differences in susceptibility to these factors may lead to an increase or decrease in peritoneal solute transport rates. Follow-up measurements of peritoneal solute kinetics are necessary to identify those patients who are at risk.

Cimetidine improves prediction of the glomerular filtration rate by the Cockcroft-Gault formula in renal transplant recipients.

Background. The glomerular filtration rate (GFR) can be predicted from plasma creatinine, age, gender, and body weight, using the formula of Cockcroft and Gault. Cimetidine improved the accuracy of GFR prediction in renal disease and also in diabetes mellitus type 2, due to inhibition of tubular creatinine secretion. We compared the accuracy and precision of GFR prediction from the Cockcroft-Gault formula without cimetidine (CG), with cimetidine (CGcim) and from the creatinine clearance without cimetidine in renal transplant recipients. Methods. CG and CGcim were calculated from plasma creatinine before and after 2400 mg of oral cimetidine during the 24 hr preceding the GFR measurement. The endogenous creatinine clearance was measured in 24 outpatients from a 24-hr urine collection (Ccr24) before cimetidine. GFR was measured as the urinary clearance of continuously infused 125I-iothalamate. Creatinine was determined with an automated enzymatic assay in plasma and with an alkaline picrate assay in urine. Results. GFR was 47.8±16.8 ml/min/1.73 m2 (mean±SD), Ccr24 was 71.8±23.1 ml/min/1.73 m2, CG was 62.2±15.2 ml/min/1.73 m2, and CGcim was 52.8±14.9 ml/min/1.73 m2. Ccr24 overestimated GFR in every patient by an average of 23.8 ml/min/1.73 m2 and CG by an average of 14.3 ml/min/1.73 m2, whereas CGcim overestimated GFR significantly less by an average 4.9 ml/min/1.73 m2 (P <0.001). The precision of CGcim was significantly better than that of Ccr24: the SD of the difference from GFR was 9.0 ml/min/1.73 m2 for CGcim and 14.5 ml/min/1.73 m2 for Ccr24 (P <0.05). Conclusion. CGcim is useful for GFR prediction in outpatient renal transplant recipients and has a far better accuracy and precision than Ccr24 and also a better accuracy than CG. We propose a strategy after kidney transplantation of one GFR measurement at baseline and follow-up with CGcim.

Antifungal Treatment of Candida Peritonitis in Continuous Ambulatory Peritoneal Dialysis Patients

Nine peritonitis episodes caused by Candida sp were diagnosed in eight continuous ambulatory peritoneal dialysis (CAPD) patients. Treatment with intraperitoneal administration of amphotericin B and 5-fluorocytosine while the peritoneal catheter was left in situ was effective in six episodes in five patients. Of the three other patients, two started again with CAPD after peritonitis had been cured, but one patient preferred to stay on hemodialysis. In four episodes, peritoneal white cell counts remained high during treatment despite negative cultures. This was probably the result of irritation of the peritoneal membrane caused by the antifungal treatment, possibly by amphotericin B. Persistently-elevated leukocyte counts during antifungal therapy, with or without signs and symptoms of peritonitis, are not necessarily an indication of treatment failure.

Estimation of the glomerular filtration rate in NIDDM patients from plasma creatinine concentration after cimetidine administration.

OBJECTIVE Glomerular filtration rate (GFR) can be estimated in patients with renal disease from plasma creatinine concentration, age, sex, and body weight according to the formula of Cockcroft and Gault. The hypothesis that this method can be improved when tubular secretion of creatinine is inhibited by cimetidine was studied in NIDDM patients. RESEARCH DESIGN AND METHODS In 30 outpatients with NIDDM and normo-(n = 10), micro- (n = 9), or macroalbuminuria (n = 11), GFR was measured as the urinary clearance during continuous infusion of 125I-labeled iothalamate. Plasma creatinine concentration was analyzed with an enzymatic assay before and after 800 mg t.i.d. oral cimetidine was given during a 24-h period. RESULTS Plasma creatinine rose in all patients after cimetidine administration and, as a consequence, the clearance calculated with the Cockcroft-Gault formula fell. The ratio of this formula and GFR decreased from 1.16 ± 0.20 to 0.97 ± 0.16 (means ± SD). This ratio tended to be smaller in the normo- (0.93) than in the micro- (0.98) and macroalbuminuric (1.00) groups. Also, 20 patients with a BMI < 30 kg/m2 had a smaller ratio than those with a BMI > 30 kg/m2 (0.92 vs. 1.07; P < 0.05). Bland and Altman analysis showed a difference of the Cockcroft-Gault formula and GFR of 12.0 ± 17.4 ml · min−1 · (1.73 m2)−1, which decreased to −3.8 ± 14.8 ml · min−1 · (1.73 m2)−1. The same analysis of 24-h creatinine clearance with urine collection and GFR showed larger standard deviations. CONCLUSIONS GFR can be estimated in an acceptable way from plasma creatinine concentration after cimetidine administration in outpatients with NIDDM. Despite a nonsignificant underestimation in normoalbuminuric and overestimation in overweighted patients, this method is superior to 24-h creatinine clearance with outpatient urine collection.

Effect of Prednisone on Renal Function in Man

To clarify the rise in plasma creatinine concentration previously observed during prednisone treatment, we studied changes in renal function in Graves ophthalmopathy patients before and after 2 weeks of either prednisone 60 mg/day or retrobulbar radiotherapy (controls). Compared to retrobulbar radiotherapy, prednisone treatment was associated with an increase in: (a) plasma creatinine concentration (from 68 +/- 4 to 76 +/- 4 mumol/l), (b) glomerular filtration rate (GFR, from 93 +/- 4 to 102 +/- 5 ml/min/1.73 m2), and (c) urinary creatinine excretion rate (from 510 +/- 40 to 570 +/- 40 mumol/h). We conclude that GFR rises during 2 weeks of high-dose prednisone administration, a rise that is not reflected by a decrease in plasma creatine concentration. On the contrary, both plasma creatinine concentration and urinary creatinine excretion increase, probably as a result of the catabolic effect of prednisone. As established by the present study, prednisone 60 mg/day is associated with protein wasting, also after 14 days of treatment.

Fluid Kinetics in CAPD Patients during Dialysis with a Bicarbonate-Based Hypoosmolar Solution

The magnitude of transcapillary backfiltration by the colloidosmotic pressure within the peritoneal capillaries compared to the effective lymphatic absorption was investigated in continuous ambulatory peritoneal dialysis patients. This was done during a 4-hour dwell period, using a hypoosmolar dialysis fluid (280 mosm/kg H2O) in 8 patients and compared to 5 of these patients using a 1.36% glucose (GS; 324 mosm/kg H2O). The low molecular weight solute transport did not differ between the two solutions. The intraperitoneal dextran 70 concentration increased during the dwell with the hypoosmolar dialysis fluid (from 770 to 945 mg/l; p = 0.000002) and decreased with the GS (from 859 to 719 mg/l; p = 0.007). With the GS the transcapillary ultrafiltration was directed towards the abdominal cavity during the dwell period. With the hypoosmolar fluid, the transcapillary ultrafiltration was continuously directed towards the circulation. In this solution, the magnitude of transcapillary backfiltration due to colloidosmotic pressure within the peritoneal capillaries was 0.4 +/- 0.1 ml/min. In conclusion, intraperitoneal markers can be used in continuous ambulatory peritoneal dialysis patients for determination of effective lymphatic absorption and transcapillary fluid passage in both transport directions.