An improved method to determine renal function using inulin and p-aminohippurate (PAH) steady-state kinetic modeling.

Steady-state clearances using inulin and PAH are the most reliable reference procedures if new test substances or techniques are developed to estimate the GFR or the of these methods we developed an open monocompartment model with an expanding distribution volume of the substance of interest. In this model we derived prescriptions for the concentration of inulin and PAH in the infusion procedure. The resulting improvement was verified by the F-test on the variance of plasma concentration in a 3-hour examination of 15 patients. The final results are of direct benefit to the patient because the number of blood samples required for the control of the steady-state plasma level can be reduced. Furthermore, we derived an individual correction of the so-called input steady-state clearance (without urine collection) which relates better to the usual output clearance of inulin or PAH. A PC-BASIC program is available that calculates the proper concentrations for the infusion and executes the complete analysis (GFR, ERPF, filtrate fraction [FF], maximal tubular transport of PAH [TmPAH] and the renal vascular resistance [RVR], each of which is related to the BSA and the age of the patient).

Determination of glomerular filtration rate (GFR) on two consecutive days using inulin in a single-sample plasma clearance method.

Reliable estimation of the GFR is essential in nephrological practice for the early recognition and follow-up of latent or residual renal disturbance. The GFR of ten healthy volunteers on two consecutive days and of 40 patients with different renal diseases were investigated by means of a plasma slope clearance technique. After injection of 5 g/50 ml inulin solution, eight plasma samples were taken at 10, 20, 30, 40, 120, 180, 240, 300 min p.i. and analyzed with the aid of a fully enzymatic method. The results were correlated on the basis of 1- and 2-compartment models (1 CM, 2 CM) and the one-sample method (1 S), using only the plasma inulin concentration of the 240 min p.i. sample. The accuracy of the GFR data of volunteers estimated in these models was checked by comparison with the standardized agewise normal values, while for the patient group we found in terms of equations of correlation: 1. GFR (2 CM) = 4.46 + 0.763*GFR (1 S), n = 31, r = 0.985 2. GFR (2 CM) = 1.27*GFR (1 CM)0.9, n = 40, r = 0.996 3. GFR (1 CM) = 0.568*(GFR[1 S] + 5.85)1.11, derived The single-sample method using inulin is closely correlated to multi-sample methods but much more suitable for patients and staff. Therefore, it is recommended for clinical use.

Experiments with continuous hemofiltration and hemofiltrate regeneration in the rat.

Experimental studies were made with continuous hemofiltration treatment for bilaterally nephrectomized rats and initial observations regarding the effects of such treatment on leukocyte and thrombocyte counts are reported. Hemofiltration of unanesthetized rats able to move freely within their cage could be continued for up to 30 h using a pump-driven ECC system. Blood parameters recorded during this treatment indicate that the detoxification was effective. In another series of experiments the water and electrolyte reabsorption capacity of the colon ascendens of healthy rats was tested by continuously supplying NaCl solution into the colon via a fistula. A large proportion, if not all, of the hemofiltrate can be discharged into the colon without diarrhoea. A final series of experiments showed that the three-stage operation (implantation of permanent catheters, connection of a permanent intestinal fistula and bilateral nephrectomy) is possible with the rat.

[Reproducible determination of the glomerular filtration rate (GFR) and the effective renal plasma flow (ERPF) in conscious rats using inulin and p-aminohippuric acid]. / Wiederholbare Bestimmung der glomerulären Filtrationsrate (GFR) und des effektiven renalen Plasmaflusses (ERPF) an der wachen Ratte mit Inulin und p-Aminohippursäure.

Estimation of the glomerular filtration rate (GFR) and of the effective renal plasma flow (ERPF) by means of the test substances inulin and p-aminohippuric acid according to the steady state clearance measurement during the drop of the plasma level after the initially injection of an depot of the indicators was examined methodologically. The procedure should be repeatable in the same animal under conscious conditions. The results demonstrate that the described method is adequate with regard to accuracy, reproducibility and sensitivity for the estimation of the GFR, whereas limitations apply to calculation of the ERPF.

[Internal medicine and clinical physiopathology]. / Innere Medizine und klinische Pathophysiologie.

Internal medicine is understood as an applied part of medicine closely connected with the patient, the task of which is care of patients. Clinical pathophysiology is understood as theoretical and experimental field of medicine the task of which is the clarification of diseases by statement of functional connections. Among other things the two specialities used the clinico-diagnostical and clinico-physiological (experimental) functional diagnostics for the solution of their task. The results are usable for the medical care immediately for the individual patient (prophylaxis, therapy, metaphylaxis, rehabilitation) or they will be for the patient's benefit as medico-theoretical knowledge (etiopathogenesis, sanogenesis, prognostics). Problems of realisation are entered at the instance of the respiratory functional diagnostic in the preliminary, basis and complex region under the aspect of personal and localisation questions of functional diagnostics.

[Evaluation of research findings of potassium metabolism through biological modeling]. / Wertung von Untersuchungsbefunden des Kaliumhaushaltes durch biologische Modellierung.

The cybernetic modelling of the water balance and the electrolyte balance has a heuristic value for the physiology and pathophysiology, by clearing up connections and open problems. This concerns problems of regulation size and regulation extension, but also the validity of reference values. Under this aspect is referred to the significance of steady state, input- and output inbalances and of the static and dynamic characteristics in the examination of the functional performance of the regulation circle. The static and dynamic compartment modelling is discussed at the instance of the potassium balance and exemplarily confirmed by findings of examinations. Here is referred to the special information value of the dynamic compartment analyse, as apart from the pool sizes (capacities) also intracorporal turnover rates (effects) are established.

[Methods for determining the glomerular filtration rate in experiments with small animals: position report of the Animal Experiment Diagnosis of Kidney Function Study Group of the Society of Nephrology of East Germany]. / Methoden zur Bestimmung der glomerulären Filtrationsrate (GFR) in Versuchen an Kleintieren: Positionsbericht der Arbeitsgruppe "Tierexperimentelle Nierenfunktionsdiagnostik" der Gesellschaft für Nephrologie der DDR.

The methods of the investigation of the glomerular filtration rate (GFR) in the animal experiment on cats and rats used at present are demonstrated as survey and the results of the basic investigations are compared. The values in cats lie between 20 and 30 ml/min/100 g kidney, in rats GFR values are between 0.6 and 1.0 ml/min/100 g body mass and 0.6-0.3 ml/min/1 g kidney. The basic values are essentially influenced by the experimental conditions and determination methods so that only clearance values within the working team concerned are comparable.

[Hypoxia, acidosis and nephrology]. / Hypoxie, Azidose und Nephrologie.

In a survey the correlations between hypoxia, acidosis and nephrology are presented. In chronic oxygen deficiency the individual aspects concern the uncertainties of erythropoietin and the carotid-sinusoidal natriuresis stimulated by chemoreceptors. The effects of acute ischaemic hypoxic reactions are described with regard to the acute renal failure. The regulatory renal function of acidification and its disturbance in chronic renal insufficiency as well as the renotubular acidosis are discussed. Finally the authors enter the influence on the renal function during positive pressure respiration (e.g. for the purpose of the normalisation of the pulmonary gas exchange in acute respiratory insufficiency) as well as on reactions of the haemodialysis (bicarbonate and acetate dialysis) to the blood gas and acid-base metabolism, taking into consideration the pulmonary function.

[Pathophysiologico-clinical aspects of so-called compensatory hypertrophy of the kidney]. / Pathophysiologisch-klinische Gesichtspunkte bei der sog. kompensatorischen Hypertrophie der Niere.

In a survey is reported on the present level of knowledge of the nephronal functional and structural adaptation in the so-called compensatory hypertrophy of the kidney. The pathogenic character of the glomerular hyperfiltration standing hereby in the centre (phenomenon of progression of chronic nephropathies) and of the final control elements influencing the residual nephrons (trade-off phenomena in chronic nephropathies) is made evident. Issuing from this the unmasking of the situations of latent glomerular hyperfiltration (GFR reserver diagnostics) is postulated as an actual task.

Accumulation of 42K and 86Rb in the organs of the rat.

42K and 86Rb were administered in combination to anaesthetized rats by the intravenous route, and accumulation of the isotopes in the organs during a few cirulatory cycles (90 sec) and after 24 hours has been studied in the rat. a) Accumulation of the two elements was identical in skeletal and heart muscle at both points of time. b) Acute (90 sec) accumulation of 86Rb slightly exceeded that of 42K in the skin, liver, brain, external and internal medulla of the kidney. Therefore, the cardiac output fractions obtained with 42K and 86Rb according to Sapirstein's method must be compared with certain corrections, and they cannot be evaluated in a combined form. c) Considerable differences were found in the accumulation of the two elements after 24 hours. The differences were ascribed to the different intra- and extracellular concentrations of the natural isotopes of the two elements and, to a lesser extent to their presumbly different "lag phenomenon".

[Determination of hepatic indocyanine green (ujoviridine) clearance using the slope-method]. / Ermittlung der hepatischen Indozyaningrüm-(Ujoviridin-)Clearance im Slope-Verfahren

1. The technique of the functional test of the liver by means of the indocyanine green (ujoviridine) test suggests to express the results of the test as a result of clearance on the basis of the slope-clearance. 2. The analysis of the curve of disappearance of the test substance in the serum could not always be traced back to a simple exponential function in a group of clinically healthy control persons (10 women at the age of 10-24 years). For the better estimation of the slope-clearance, therefore, the rinsing effect of the liver should be preferred by means of the analysis of a composed (twofold) exponential function. 3. In the two investigation methods the results of the clearance values were not symmetrically distributed so that as parameters of estimation at first only the mean values of density are used. 4. According to this only orientating study the values of the ujoviridine clearance are below 720 ml/min, assuming a simply exponential rinsing function, or 500 ml/min, respectively, taking as a basis the composed exponential rinsing function below the mean values of density.

[Pathogenicity of glomerular hyperfiltration, a question of glomerular tolerance?]. / Pathogenität der glomerulären Hyperfiltration, eine Frage der glomerulären Toleranz?

As an introduction the concept of the hyperfiltration nephropathy is described. Since it was essentially derived from animal-experimental observations on the rat, the question after the importance for human medicine arises. To this is now argued that a comparable nephronal hyperfiltration possesses a species-different pathogenicity, since the glomerular tolerance to among others the mesangial protein load is also species-different. From this the diagnostic demand for the determination of the glomerular filtration reserve for the recognition of the glomerular hyperfiltration and for the investigation of the microalbuminuria for recognizing the glomerular tolerance.

[Development of a model as a pathophysiologic study method in clinical and experimental nephrology]. / Modellbildung als pathophysiologische Arbeitsmethode der klinischen und experimentellen Nephrologie.

After explanations concerning principal qualities of the models follow examples from nephrology about theoretical and concrete modelling. Consequences for the renal functional, performance and reagibility diagnostics are discussed. The ability of mathematical modellings for statements is shown at the instance of the ureal plasma kinetics in apparative peritoneal detoxication methods and in connection with investigations about the implantable kidney as well as supplemented by explanations concerning the dynamic compartment modelling of the potassium balance.

[Functional differentiation of residual volume changes and problems of evaluation from the physiopathologic viewpoint]. / Funktionsdiagnostische Differenzierung der Residual-volumenveränderung und Befundungsprobleme aus pathophysiologischer Sicht.

The ascertainment of the residual volume is a very important method for pulmonary emphysema diagnosis. But there are problems of estimation on the basis of this residual volume. The usual relation (RV/TLC) greater than 0,35 as measure for an emphysema will be considered critically. In this way functional relations will be given which allow a more secure emphysema diagnosis. They use as measure comparisons between RV and fit reference volumes, such as normal values of RV, VC or TLC. These equations make it possible to differentiate between structural and functional disturbances.

[Is the inulin (and PAH) clearance test obsolete in renal functional diagnosis?]. / Ist die Inulin (und PAH-) Clearance in der renalen Funktionsdiagnostik überholt?

1. It could be confirmed that the endogenic creatinine clearance overestimates the GFR. This overestimation increases with the restriction of the glomerular filtration. 2. By the biphasic pump-regulated permanent infusion of inulin and PAH a constant equilibrium was reached and the clearance was calculated according to the classical formula (output method) as well as from the addition of the test substance (input method) and compared. 3. The comparison of the two clearance techniques results in significantly higher value for inulin as well as for PAH in the input technique. 4. By clearance equations the relation of input and output clearance can be made. The correlation coefficient for the different investigation techniques for the estimation of the inulin clearance was 0.83, for the PAH-clearance 0.88.

[The slope clearance method in renal functional diagnosis. J-131-hippurate clearance is used as an example]. / Betrachtungen zur Slope-Clearancemethodik in der renalen Funktionsdiagnostik am Beispiel der J-131-Hippurat-Clearance.

The clinical relevance of the clearance of radiopharmaca is controversial in literature. The cause for this are in our opinion the different methods of evaluation which either make difficult or make impossible a comparison of individual results. The late phase of the disappearance (at least 70 and 100 min p.i.) possesses a high value under the aspect of renal diagnosis, since by its means with a high approximation the renal function may be established itself.

[Physiological-pathophysiological evaluation of possibilities and limits of unilateral renal function tests]. / Physiologisch-pathophysiologische Einschätzung zu Möglichkeiten und Grenzen der seitengetrennten renalen Funktionsdiagnostik.

1. Issuing from the clinical method of proceeding in side-separated diagnosis of the renal function under theoretical aspect a survey orientation for the renal global function is tried. 2. The method orientation is done according to semiquantitative and quantitative valuation. The isotope and contrast remedy urography, the functional tests after Howard, Rapoport and Stamey, the conventional side-separated estimation of the clearance, the isotope sequence scintigraphy as well as the diagnostics of the renal and intrarenal haemodynamics (renin determination, measuring of the renal plasma flow by means of PAH and other indicators [133-xenon-wash-our-technique]). 3. Finally a valuation of the method concerning the side-separated diagnostics of the renal elimination function as well as of the stenosis of the renal arteries is done taking into consideration the performability of the investigation methods in the clinic.

[Evaluation parameters of the glucose-infusion-test (GIT) from the biocybernetic point of view (author's transl)]. / Bewertungsparameter zum Glukoseinfusionstest (GIT) aus biokybernetischer Sicht.

It was attempted to evaluate the usual parameters of the glucose-infusion-test (GIT) from the biocybernetic point of view by considering the blood sugar and insulin-behaviour as a dynamic characteristic according to suddenly elevated glucose level. The insulin response is characterized by biphasic behaviour and could demonstrate a combined proportional, integratuel and differential regulation type (PID-regulation). The usual parameters of the glucose-infusion-test for the blood sugar and insulin behaviour contain essential biocybernetically important informations, certain restrictions and additional suggestions are given.