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.

[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.

[Effect of indomethacin on the vital prognosis and homeostasis of rats with kidney insufficiency]. / Indometacineffekt auf Vitalprognose und Homöostaselage niereninsuffizienter Ratten.

The medicamentous-therapeutic modulation of pathogenic hyperfiltration of residual nephrons by the prostaglandin synthesis inhibitor indomethacin was evaluated again. The experimental study of inbred wistar rats including a low indomethacin dosage of 1.5 mg/kg BW, a strong reduction of renal parenchyma (80%) and an increased food protein content of 40% did show the known results: indomethacin may impair the vital prognosis of severe renal injury.

[Simultaneous determination of the GRF and the ERPF (effective renal plasma flow) using a single blood sample in the slope clearance with 99mTc-DTPA and I 131-hippurate]. / Simultane Bestimmung der GFR und des ERPF durch nur eine Blutprobe bei der Slope-Clearance mit 99mTc-DTPA und 131J-Hippurat.

In patients with various indications to renal split function diagnostics the plasma slope clearance of the Tc99m-DTPA and J131-Hippurate to the estimation of GFR and ERPF were performed with two or three blood samples in the monocompartment model (1 KM). In comparison these functional parameters were calculated on the basis of the only least blood sample (single-point procedure--EPV). The results of linear regression GFR (1 KM) = 12.7 + 0.978 * GFR (EPV), r = 0.986, N = 102 or ERPF (1 KM) = 22 + 1.13 * ERPF (EPV), r = 0.889, N = 68 may recommend the use as patient-safe procedure especially in poor venous access. Two short BASIC programs for estimation of GFR and ERPF are presented and the error ranges discussed.

[Ergometric results of r-erythropoietin treatment of hemodialysis patients]. / Ergometrische Ergebnisse bei r-Erythropoietin-Behandlung von Hämodialysepatienten.

To investigate the effect of partial correction of anemia in patients maintained by chronic intermittent hemodialysis on exercise capacity, patients underwent a bicycle acido-ergometry before and after treatment with recombinant human erythropoietin. The results demonstrate a (subjective) improvement of exercise capacity without any evidence for that in the pH values.

[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.

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).

[Pathophysiologic-nephrologic hypothesis of the protective function of an endogenous natriuretic and digoxin-like substance (endoxin) for residual nephrons]. / Pathophysiologisch-nephrologische Hypothese zur protektiven Funktion der endogenen natriuretischen und digoxinähnlichen Substanz (Endoxin) für Residualnephrone.

A dualistic function for the natriuretic ATP.inhibiting factor is formulated on the basis of a phenomenon like compensatory renal adaption of residual nephrons: 1. Support of the tubular sodium excretion to the maintenance of homoeostasis of the organism. 2. Inhibition of the forced up vasodilation of the afferent glomerular vessel. It should suggested that the renal vasoconstrictive effect is a part of a protective system for residual nephrons against the pathogenic hyperfiltration and hyperperfusion.

[Steps for solutions and hindrances in progress in relation to an implantable bio-artificial hemofilter-intestine-hybrid kidney]. / Lösungsschritte und Hindernisse auf dem Wege zu einer implantierbaren bioartifiziellen Hämofilter-Darm-Hybridniere.

On the view of 1989 older and modern developments to a bioartificial implantable hybrid kidney are presented. To the realization proof of the implantable hemofilter-intestine-hybrid kidney the routes were described in an experimental rat model to the plasmakinetic simulation of the urea and sodium level as a marker of the hybrid kidney functions. The results of the bioartificial hemofilter-intestine-hybrid kidney development are presented, but significant detail problems must be solved, especially the hemofilter biocompatibility problem.

Optimization of hemofilters for the development of implantable artificial kidneys.

The concept of developing an implantable artificial kidney demands, in addition to the regeneration of endogenous filtrate, a small hemofilter with a high filtration rate. Conventional capillary filters are limited in their capacity to yield adequate filtrate, even if the number of capillaries is increased. To improve filter design so as to modify flow conditions for filtration rate augmentation, it is necessary to consider such factors as blood flow through a single capillary, wall shear rate, and transmembrane pressure (ptm) in in vivo applications, where such biological considerations as blood pressure, blood flow, and flow characteristics of blood are important. These requirements lead to a completely new filter type, the "curl filter," characterized by a large effective filtration surface in a relatively small number of hollow fibers in which optimal flow conditions prevail.

[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.

[The growth of rats in renal compensatory adaptation in feeding with a supplemented diet of hydroxy-analogs of essential amino acids]. / Das Wachstum von Ratten während renaler kompensatorischer Adaptation bei Ernährung mit einer durch Hydroxyanaloga von essentiellen Aminosäuren supplementierten Diät.

Rats were fed protein-restricted after unilateral nephrectomy (6.7% casein). Comparatively other animals were fed with experimental diets, at which 20% of the casein have been replaced by Ketosteril or a mixture of hydroxy acid. The constituents of this mixture are in accordance with the molar relation of all Ketosteril components. However, sodium solts of hydroxy acids of leucine, isoleucine and valin replace the corresponding keto acids of Ketosteril. The other components of the mixture consist of free amino acids. The efficiency of protein utilisation was judged by the relation of increased body weight and nitrogen intake. The efficiency of protein utilisation of both supplemented diets is 2.5 times higher compared with the casein diet.

[Studies of animal experiment models of the behavior of the glomerular filtration rate in acute changes of dietary protein consumption]. / Tierexperimentelle Modellstudien zum Verhalten der glomerulären Filtrationsrate (GFR) bei akuter Anderung des Nahrungsproteinangebotes.

The glomerular filtration rate (GFR) and the tubulo-secretoric transport maximum of para-aminohippuric acid (TmPAH) were examined in acute feeding trials (pellets, flesh) and after infusion of furesemide, dopamin and glucagon in normal and unilaterally nephrectomized Wistar rats. The aim of the study was to investigate the start process of GFR rise in a further experimental model (apart from the hyperfiltration in residual nephrons) and to confirm the so-called paradoxical GFR changes. The investigations of acute protein-loading induced GFR changes were without results, whereas a GFR rise could observed during intraarterial infusion of isotonic saline solution. A paradoxical GFR behaviour was demonstrable under high glucagon application.

[Contribution of animal experiments in the problem of a long-term indomethacin therapy in advanced nephron loss]. / Tierexperimenteller Beitrag zur Frage der Indometacin-Langzeittherapie bei fortgeschrittenem Nephronverlust.

Residual nephrons are subject to compensatory adaptation at which the glomerular hyperfiltration and convection of macromolecules (proteins) are of pathogenic character in the progression of nephropathy. The influence of indomethacin at dosages of 2 or 3 mg/kg body weight/day was investigated in long-term feeding trials (8 months) on inbred female Wistar rats after unilateral nephrectomy and additional resection of both kidney poles. The results show a significant deterioration of vital prognosis under indomethacin medication independently of the dosage.

[Standardization of methods and assessment of conventional and radionuclide clearance investigations: recommendations of the Renal Diagnostics Study Group of the Society of Nephrology, GDR]. / Vereinheitlichte Methodik und Beurteilung der konventionellen und nuklearmedizinischen Clearance-Untersuchungen: Empfehlungen der Arbeitsgruppe "Nierenfunktionsdiagnostik" in der Gesellschaft für Nephrologie der DDR.

Recommendations of the Study Group "Renal Function Diagnostics" of the Society of Nephrology to the performance of the steady state clearance using inulin or PAH and the slope clearance with radionuclides for estimation of effective renal plasma flow are presented. These investigations are indicated in the early recognition and follow-up of latent or residual disturbance of the renal function in the creatinine-blind area. Recommendations have been done on selection and dosage of test substances, timing of examination and evaluation of results.

[Acute oral protein administration in the diagnosis of kidney function and causal pathogenetic correlations]. / Akute orale Proteinbelastung zur renalen Leistungsdiagnostik und kausalpathogenetische Zusammenhänge.

In a literature review it was reported on the performance-orientated diagnostic determination of the glomerular filtration rate by acute oral protein load in man. Recommendations to the standardization of the test realisation are presented. The results of the glomerular filtration reserve--being derived from acute intraindividual changes of the creatinine short-term clearance after an oral protein load--are described in dependence on the renal starting situation. The causal-pathogenetic relations are represented in consideration of the natriuretic hormone and of the pathophysiological model character of the GFR-provocation test to hormonal starting processes, respectively.

[Hemorheological/hemodynamic study on miniaturized capillary filters in the concept of an implantable artificial kidney]. / Hämorheologische/hämodynamische Untersuchungen an miniaturisierten Kapillarfiltern im Entwicklungskonzept für eine implantierbare künstliche Niere.

The conception of an implantable kidney provides the substitute of the non-functioning kidney by a technical-biological system. The filtration function is to be performed by a capillary hemofilter. The results obtained in an open test circulation on 3 filters produced by optimum aspects were represented and compared with the physiological performance parameters of the kidney. The special importance of the construction of the flow conditions in the single capillary is accentuated as the fundamental aspect for additional optimization. An optimized capillary filter produced the necessary filtration rate for maintaining the homeostasis on condition of a low-protein diet and an increased level of blood urea. The changes of the hemorheologic parameters is to come up by an adequate absorption of fluid in the colon.

[Modelling and simulation of urea balance in a rat model on the condition of large intestine infusion analogous to the ultrafiltrate as a contribution to the development of an implantable intestinal hybrid kidney]. / Modellierung und Simulierung des Harnstoffhaushaltes im Rattentiermodell unter den Bedingungen der ultrafiltratanalogen Dickdarminfusion als Beitrag zur Entwicklung einer implantierbaren Darmhybridniere.

The urea kinetics in blood plasma is discussed for the animal model in rats in the development conception of an implantable artificial kidney, in which the filtration process is received energetically endogenically by a technical hemofilter whereas the ultrafiltrate procedure takes place by intestinal reabsorption and elimination of the end-products. The underlying monocompartment model contains the elements plasma, hemofilter, intestine including their urea turnover rates. Further on a special model conception is developed for the animal experimental designation of the selective urea reflecting power of the intestinal mucosa. The hemofilter-intestine-hybrid kidney-system has chanced to be in order if the experimentally ascertained quantities of the preliminary experiments will be inserted simultaneously for essential parameters in the model experiment.

[The selective elimination function of the colon in a rat model for the substances water and urea in long-term experiments as a contribution to the development of an implantable hemofilter-intestine-hybrid kidney]. / Untersuchungen zur selektiven Eliminationsfunktion des Kolons im Rattenmodell für die Substanzen Wasser und Harnstoff im Langzeitversuch als Beitrag zur Entwicklung einer implantierbaren Hämofilter-Darm-Hybridniere.

The investigations on the selective elimination and preservation function of the colon represented one of the numerous problems in the development of an implantable hemofilter-intestine-hybrid kidney. The assumption of an ideal reflection of urea on the intestinal mucosa and the ability of water absorption of the colon had to be checked. A fluid which is nearly analogous to the ultrafiltrate with different urea concentrations was infused into the colon of rats by a cecocutaneous catheter fistula during two-phasic long-term experiments. The renal and enteral urea elimination rates were defined. The apparent reflection coefficient for urea of the colon amounted 0.5 to 0.6 in an infusion rate of 80 ml/day. The ability of water absorption of the colon in rats of nearly 300 g of weight could be increased up to 200 ml/day during slow and continuous adaptation in the infusion quantity.