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The glomerular filtration rate was measured in the sick elderly patients using the single shot 51Cr EDTA method. As would be expected, such patients have worse renal function than the fit elderly. The filtration rate can be usefully predicted from either blood urea or serum creatinine, but a superior prediction is obtained when these factors are combined using a formula derived from multiple regression analysis.
The approximate size of the H strain of non-A, non-B (NANB) hepatitis virus was determined by filtration through polycarbonate membranes. The accuracy and reproducibility of such filtrations were monitored by filtering selected reference viruses. These studies indicate that strain H, representative of the principal blood-borne NANB hepatitis virus, is 30-60 nm in diameter. It is therefore highly unlikely that NANB hepatitis virus is a retrovirus, as has been suggested.
BACKGROUND: For many years, hypertension has been related to long-term survival of patients and kidney grafts, although the nature of this relationship has not been completely defined. The aim of this study was to analyse the influence of early glomerular filtration rate on post-transplant hypertension and on graft survival. METHODS: A total of 432 kidney transplanted patients on cyclosporin therapy, with a functioning graft for at least 1 year, were studied. They were divided into two groups depending on their early creatinine clearance: group A [<60 ml/min (n=270)] and group B [>60 ml/min (n=162)]. RESULTS: There were no differences in sex, aetiology of renal failure, number of retransplants, PRA, HLA mismatches and pre-transplant blood pressure. One year after transplantation, blood pressure was higher in group A (systolic BP 148/diastolic BP 86/mean BP 117) than in group B (systolic BP 140/diastolic BP 82/mean BP 111) (P<0.003). We observed a negative correlation between early creatinine clearance and 1-year blood pressure (P<0.01). Five and 10 year graft survival was 60 and 37% in group A and 87 and 69% in group B, respectively (P<0.000). A multivariate Cox analysis showed that 1-year blood pressure (P<0.0029, RR=1.76) and early creatinine clearance (P<0.000, RR=3.27) had a significant influence on graft survival. CONCLUSIONS: The 1-year post-transplant blood pressure is a non-immunological risk factor in long-term graft survival. Patients with a lower initial glomerular filtration rate are more susceptible to the development of secondary hypertension and worse graft survival.
UNLABELLED: Nonsteroidal antiinflammatory drugs (NSAIDs) have become increasingly popular in the treatment of perioperative pain. Due to concerns that cyclooxygenase inhibition may adversely affect renal function, these drugs are often not used in geriatric surgical patients. However, the perioperative effect of NSAIDs on renal blood flow (RBF) and glomerular filtration rate (GFR) has not been assessed. Therefore, using a prospective, controlled, double-blinded study design, we evaluated the effect of diclofenac on RBF and GFR in 20 patients (>65 yr) undergoing open reduction and internal fixation of the femur. All patients were normovolemic before the study. A standardized general anesthetic was administered. On induction of anesthesia, patients in the diclofenac group received an IV bolus of diclofenac (0.7 mg/kg) followed by a constant infusion (0.15 mg x kg(-1) x h(-1)) until the end of surgery. In the saline group, an equal volume of saline was administered. During four time periods (equilibration, anesthesia, surgical, recovery), GFR and effective renal plasma flow (ERPF) were measured by inulin and paraaminohippurate clearance, respectively. After the induction of anesthesia and throughout the surgical period, ERPF and GFR were significantly decreased compared with preoperative baseline values. However, no difference was demonstrated between the groups. These results suggest that, in geriatric surgical patients, the adjuvant administration of NSAIDs does not adversely affect renal function. IMPLICATIONS: As determined by inulin and paraaminohippurate clearance, the intraoperative administration of diclofenac does not decrease glomerular filtration rate or effective renal plasma flow in normovolemic geriatric patients. Therefore, diclofenac may be administered during the perioperative period.
In order to evaluate the effect of microaggregate blood filtration on pulmonary status, hemostatic status, and incidence of infection, a prospective study was performed on patients undergoing elective total hip replacement for osteoarthritis. Forty patients were randomized to either a 260 micron standard filter group or a 20 micron microaggregate filter group. Patients were monitored pre- and postoperatively for changes in arterial blood gases and in vitro test of hemostasis. Postoperative measurements were also made of the total volume of blood collected from the operative wound drain and of the number of infections incurred by patients in the two filter groups. Average transfusion was 4.0 units for the standard filter group and 4.6 units for the microaggregate filter group. Results showed that postoperatively, either immediately or after 48 hours, there were no statistically significant differences (p greater than 0.05) between either filter group for any of the tests of pulmonary or hemostatic function evaluated. For infection no trends were found to suggest that microaggregate filters conveyed any protective effect. These data suggest that routine microaggregate blood filtration of up to 5 units of blood is not required.
In an informal survey, poor correlation was found between 24-hour creatinine levels and glomerular filtration rates calculated from nuclear medicine studies in spinal cord injury patients. It was speculated that the discrepancies were because the nomograms used in the calculations did not take into account differences in body fat distribution for this patient group. Twenty-five chronic spinal cord injury patients were prospectively studied to compare glomerular filtration rates (GFR) using the nomograms based on height and weight and those using renal depth determined by ultrasound. It was found that the renal depth determined by nuclear medicine was significantly less than that determined sonographically. The mean difference between the total nuclear medicine-based GFR and total ultrasound-based GFR was 17.576 ml +/- 15.449 ml (P < or = 0.001). It was found that there was a significant difference between calculated GFRs based on renal depths as determined by the different methods. In addition, calculated GFRs based on ultrasound-determined depths corresponded more closely to 24-hour creatine clearance levels and with a smaller degree of error than those using renal depths determined by the nuclear medicine nomograms.
In a previous study using dogs whose renal function was rendered asymmetric by unilateral infarction, the efficacy of technetium-99m (99mTc) DTPA and DMSA in measuring differential glomerular filtration rate (GFR) was demonstrated. The present study was undertaken to determine whether the same techniques were applicable to unilateral ureteral obstruction. Five normal dogs and nine dogs with partial unilateral ureteral obstruction had determination of glomerular filtration rate by standard techniques using constant infusions of iothalamate and creatinine after ureteral catheterization. These results were compared with total GFR as measured by single injection of 99mTc DTPA and analysis of the plasma disappearance curve. Calculated differential GFR was obtained by multiplying total GFR from double exponential analysis of this curve (DTPA2) by each of three measures of differential function. These included the percent differential uptake of 99mTc DTPA and 99mTC DMSA in the posterior projection as well as the geometric mean of 99mTc DMSA uptake. There were good correlations between differential GFR determined by iothalamate clearances at ureteral catheterization and all noninvasive methods involving radionuclides and DTPA2 ( r = 0.93-0.99). Single exponential analysis of the 99mTc DTPA plasma disappearance curve was less satisfactory than double exponential analysis. These results and those reported previously support the use of radionuclides in the determination of differential GFR in a variety of clinical situations.
A technique for functional radionuclide imaging of renal mean transit time and glomerular filtration rate from the results of gamma camera renography with a computer is described. The method uses deconvolution analysis on each pixel time-activity curve. The images of both parameters are of good quality except in cases of very low glomerular filtration rate. They effectively summarize the transit and uptake information available from the renogram and should prove a valuable adjunct in its routine analysis.
Using 99Tcm-diethylenetriaminepentaacetate (DTPA) an acceptable estimate of glomerular filtration rate (GFR) can be obtained in adult patients by the equation GF (ml/min) = (0.14 x W + 5) x 1000 x k, where W is the 'ideal' body mass (kg) and k the slope determined by two plasma samples. This has been verified in comparison with the results of the Russell (two samples) and Christensen (one sample) methods in 50 patients. The procedure, which does not require determination of the injected dose, could be useful in patients undergoing sequential renal scintigraphy with 99Tcm-DTPA, for example, to check a doubtful value of glomerular filtration obtained by external counting.
Insufficient filtration and over-smoothing are misleading processes in the quantification of time-activity curves. The optimum filtration requires a good knowledge of the frequency spectrum and relative amplitudes of the data and superimposed noise. Due to variations in biomedical data, it is very difficult to adjust the filter for individual cases. To overcome this problem a new method of noise reduction is proposed. In this method the time-activity curves are transformed into a low frequency (linear) curve that can be filtered heavily without significant distortion of the real data. The theory of the proposed filter and the results of its comparison with three-point filter, five-point filter and data bounding methods are presented. The comparison was performed using deconvolution analyses of simulated renograms. The results show that the proposed filter causes minimum distortion of the renogram and impulse retention function in terms of the root mean square error and the peak of the renogram. Moreover, the filter is much less sensitive to over-smoothing (number of filter iterations), the signal-to-noise ratio and the mean transit time of the renogram compared with other filters.
A high-pressure liquid chromatographic method was developed to measure nonradioactive iothalamate in serum and urine for use in estimating glomerular filtration rate (GFR). This method was used to study the renal handling of cibenzoline, an experimental antiarrhythmic drug. The mean cibenzoline clearance was 3.5 +/- 2.5 (SD) times the glomerular filtration rate. The clearance of non-protein-bound cibenzoline was seven times GFR, indicating excretion by the renal tubular secretory pathway for organic bases. This drug, at the doses used, did not lower creatinine clearance, indicating that the effect of basic drugs competing with creatinine for the base secretory pathway appears to be dose and drug dependent.
Calves were sensitized to tuberculin and histoplasmin. The delayed-type hypersensitivity skin response to these antigens was produced and the diameter of induration measured. Repeated skin tests prior to filtration demonstrated that the amount of induration produced by these skin tests was closely reproducible. Histoplasmin or tuberculin-coated columns were then introduced into a closed circuit extracorporeal thoracic duct circulation. A significant (P is less than 0.01) reduction or ablation of the delayed-type hypersensitivity response was obtained to the antigen used to coat the column. In contrast, no significant reduction occurred in the skin test response to the other antigen. Repeated skin tests to both antigens after the cessation of filtration showed a gradual rise toward prefiltration levels in the skin test to the filtered antigen. The results of these experiments indicate that a selective population of T lymphocytes can be removed from an in vivo system. The removal of these cells can selectively reduce a delayed-type hypersensitivity skin test response to a particular antigen. These results are consistent with the hypothesis that a type of in vivo selective immunosuppression can be produced by antigen-coated columns when they are placed in an extracorporeal thoracic duct lymph circulation system.
BACKGROUND: Historically, ex vivo physiological evaluation of cadaveric renal allografts has been limited to assessing perfusate flow (PF) during hypothermic perfusion preservation (HPP). Using a small animal model, we have previously described a method for continuous monitoring of glomerular filtration rate (GFR) during HPP. Our study was undertaken to determine if monitoring GFR and PF during HPP distinguished kidneys subjected to preretrieval warm ischemic (WI) injury more reliably than PF alone. METHODS: In situ WI was induced in Lewis rats (n=10) by extrinsic occlusion of the suprarenal aorta for 30 min. After in situ cold perfusion and retrieval, the left kidney underwent 16 hr of HPP. Nonischemic (NI) control kidneys (n=10) were retrieved in the absence of suprarenal aortic occlusion. Longitudinal changes in PF, GFR, and filtration fraction (FF) during HPP were compared in WI versus NI kidneys (FF=GFR/PF x 100%). RESULTS: PF remained the same in both cohorts throughout HPP. GFR, however, increased to a significantly greater degree in WI versus NI kidneys during the first 4 hr of HPP (713+/-401 vs. 26+/-23%, respectively) (P<0.05). The increase in FF at 4 hr was 1203+/-696% in the WI kidneys versus 83+/-46% in the NI controls (P<0.05). CONCLUSIONS: In contrast to PF alone, measurement of both PF and GFR distinguished kidneys subjected to pre-WI from NI controls. The data provide a means to determine if monitoring of both GFR and PF during HPP will predict short- and long-term renal allograft function more reliably than PF alone.
ABSTRACT-We examined the mechanisms and the adhesive molecules mediating platelet-neutrophil adhesion in patients with septic shock. Neutrophils, platelets, and platelet poor plasma (NPPP) were isolated from 12 normal volunteers. Platelets and neutrophils were stimulated with platelet poor plasma (SPPP) removed from 12 patients in septic shock. Cell adhesion was assessed by filtration through 5-microm pore filters and by flow cytometry. Blocking monoclonal antibodies were used against the platelet and neutrophil surface receptors glycoprotein complex IIb/IIla, P-selectin, ICAM-2, CD11a, CD11b, and CD18. The filtration pressure (Pi) of cells suspended in SPPP was significantly greater than that of cells suspended in NPPP (24 +/- 1.0 mmHg vs. 14 +/- 1.0 mmHg; P< 0.05). The difference between the Pi of cells suspended in SPPP or NPPP (deltaPi SPPP-NPPP) in the presence of monoclonal antibodies anti-CD41, anti-CD62P, abciximab, anti-CD11a, anti-CD11b, and anti-CD18 was significantly less than the APi SPPP-NPPP of cell suspensions without the addition of these monoclonal antibodies (P < 0.01). The greatest reduction in Pi occurred when platelet receptor P-selectin was blocked simultaneously with the CD11b receptor on the neutrophil as compared to all other single blocking monoclonal antibodies or combinations of monoclonal antibodies. The mean fluorescence of activated platelet CD63-PE binding to neutrophils suspended in SPPP was significantly greater than that of cells suspended in NPPP (780 +/- 130 Ifu vs. 295 +/- 35 Ifu; P < 0.05). The greatest attenuation in mean fluorescence occurred by blocking the P-selectin receptor on the platelet simultaneously with CD11b receptor on the neutrophil. We conclude that platelet-neutrophil aggregation is increased in septic shock. This aggregation is mediated by the interaction of multiple platelet and neutrophil surface receptors. The platelet receptor P-selectin and the neutrophil receptor CD11b/CD18 appear to play the most important role in these interactions.
Insulin-like growth factor-1 has been safely administered to humans with chronic renal failure in an attempt to increase glomerular filtration rate. The results of short-term studies have been encouraging. Further studies will be required to better define the role of this or other growth factors in increasing glomerular filtration rate in patients with chronic renal failure.
Delayed graft function is a form of postischemic acute renal failure. It lowers glomerular filtration rate in large part by depressing the glomerular transcapillary hydraulic pressure difference, the driving force for the formation of filtrate. Loss of proximal tubule cell polarity, impaired sodium reabsorption and tubuloglomerular feedback-mediated afferent arteriolar constriction are all implicated. A link between delayed graft function and chronic allograft injury is evident. The ensuing impairment of graft survival makes urgent the need for further elucidation of delayed graft function and a search for an effective therapy.
The level of glomerular filtration rate can be estimated from the serum creatinine concentration and other easily measured patient variables from prediction equations developed using multivariable regression techniques. Recently, a new equation has been developed from the Modification of Diet in Renal Disease study, which is more accurate than other equations and more accurate than measurement of creatinine clearance. The authors recommend using prediction equations in clinical practice to estimate the level of glomerular filtration rate.
We performed a placebo-controlled trial on the effects of a combined antihypertensive treatment with delapril, a new nonsulfhydryl angiotensin-converting enzyme inhibitor, and indapamide, a sulfonamide diuretic. We studied 28 elderly patients aged 65-85 years (mean age, 69 +/- 1 years) who took 30 mg delapril in combination with 1.25 mg indapamide once daily for 24 weeks. In the present study (performed simultaneously with our trial on the effects of delapril/indapamide on left ventricular mass in elderly patients with hypertension and on the same patients), we report the effects of this drug combination on glomerular filtration rate. Sitting arterial pressure (mean +/- SE) decreased from 156 +/- 1. 5/101 +/- 1 mm Hg at baseline to 133 +/- 1/73 +/- 1 mm Hg at the end of the 24-week treatment period (p < 0.0001). No significant changes in heart rate or episodes of orthostatic hypotension were observed. Glomerular filtration rate increased from 91.8 +/- 4.42 mL/min at baseline to 106.3 +/- 4.5 mL/min (p < 0.001) at the end of treatment. Our results show that the combination of delapril and indapamide is effective in the elderly hypertensive patient, with a favorable effect on the prevention of deterioration of kidney function.