Determination of the glomerular filtration rate by identification of sinistrin kinetics.

A computer-based method of system identification and estimation of parameter variance for two-compartment models matched to dynamic sinistrin concentration profiles for the determination of glomerular filtration rate is described. Thereby a procedure for the judgment of the optimal sampling time horizon is presented. Since single-injection techniques are suspected of yielding systematic overestimation of the glomerular filtration rate, a method is demonstrated confirming that such a technique employing sinistrin kinetics can be used to correctly determine the glomerular filtration rate. The validation of the system parameters gained by the single-injection method is made through prediction of the concentration contour under a constant infusion regimen in the same subject on a different occasion. This was performed in healthy controls and in patients with various degrees of renal insufficiency. Upon consideration of the dependence of the clearance estimates and their variances on the protocol duration in test subjects examined from four to ten hours, an adaptive design of the protocol length is developed.

A rapid immunocytochemical assay for CMV detection in peripheral blood of organ-transplanted patients in clinical practice.

This study describes clinical experience with a rapid method for diagnosis of cytomegalovirus infection in organ-transplanted patients, based on the detection of CMV-specific antigens in peripheral polymorphonuclear cells with a mixture of monoclonal antibodies. This CMV-pp65 assay was formerly called the "CMV immediate early antigen assay." A group of 180 organ-transplanted patients were examined with this assay; 75 of them could be observed from the date of transplantation. These 75 patients consisted of two groups: 59 kidney transplant patients receiving no CMV hyperimmunoglobulin prophylaxis (group I), 13 heart-transplanted patients, and 3 liver transplanted patients receiving prophylaxis (group II). Group III consisted of 105 patients who had been transplanted ca. 2 years before starting this study. In group I, 26 (44%) were CMV-pp65-positive (13 primary and 13 secondary infections). Fifteen of these 26 (58%) positive patients showed clinical symptoms of CMV infection. Eleven of these 15 (73%) were primary infections. Symptomatic patients had significantly more CMV-pp65-positive cells than asymptomatic patients; 12 patients showed a high number of positive cells and 11 of them developed severe CMV illness. Thirty-three patients were CMV-pp-65-negative (22 CMV IgG-sero-positive, 11 CMV IgG-seronegative). None of them had symptoms of CMV infection. In all patients of group I there were 36 periods of graft dysfunction in which CMV infection had to be differentiated from transplant rejection. In 10 out of 36 there was a CMV-pp65-positive test result and subsequent seroconversion. Treatment of viral infection resulted in improvement of clinical problems. In the remaining 26 episodes no CMV-pp65-positive cells were detected: in 17 cases graft dysfunction was caused by rejection, in 9 cases by other complications. In group II, 13 of 16 patients (81%) were positive in the CMV-pp65 assay (6 primary infections, 7 secondary infections). However, none of them showed clinical signs of CMV infection, regardless of the number of positive cells. No CMV-related graft dysfunction was observed. In group III, CMV infections did not play an important role. The experiences described suggest that this test is a valuable tool in early CMV diagnosis and in differentiating CMV-dependent graft dysfunction from other graft dysfunctions. It allows prompt therapeutic intervention.

Essential trace elements in humans. Serum arsenic concentrations in hemodialysis patients in comparison to healthy controls.

Serum arsenic concentrations of persons suffering from renal failure and undergoing hemodialysis treatment (n = 85) and of healthy controls (n = 25) were determined by hydride-generation AAS technique after microwave digestion. The results were evaluated by comparing the values of both groups, considering physiological factors and individual data, as well as comorbid conditions of the hemodialysis (HD) patients. Serum arsenic levels were diminished in the patient group compared with controls (mean values 8.5 +/- 1.8 ng/mL vs 10.6 +/- 1.3 ng/mL). Furthermore, additional diseases within the hemodialysis group, particularly injuries of the central nervous system (CNS), vascular diseases, and cancer, were correlated to occasionally markedly decreased serum arsenic concentrations. It was concluded that arsenic homeostasis is disturbed by HD treatment and certain additional diseases. Desirable arsenic concentrations in the body seem to be reasonable. This consideration results in the conclusion that arsenic could play an essential role in human health. Thus, reference arsenic concentrations in different human tissues and body fluids should be established in order to recognize not only arsenic intoxication, but also arsenic deficiency. Perhaps arsenic deficiency contributes to the increased death risk of HD patients, and therefore, arsenic supplementations for patients with extremely low serum arsenic concentrations should be taken into account.

Nature and rate of vascular refilling during hemodialysis and ultrafiltration.

The change of blood volume, of blood and plasma density (rho b, rho p) following a short ultrafiltration pulse (duration: 20 min; mean rate -35 ml/min) within the first hour of hemodialysis was analyzed in 13 hemodynamically stable patients (30 single measurements). Protein concentration of refilling volume (7 g/liter) was calculated from its density (1009.25 +/- 3.7 kg/m3, at 20 degrees C) and from the linear relationship between plasma density and protein concentration (cp) of uremic plasma samples (rho p = 1007.46 + 0.2422 x cp). The filtration coefficient (Lp,calc) determined from a relation derived from Starling's hypothesis was 5.6 +/- 1.4 ml/(min.mm Hg.50 kg lean body mass); N = 13, mean +/- SD, minimum 3.2, maximum 8.0. A model describing the dynamics of blood and plasma volume was developed. It was fit to on-line measurements of relative blood volume changes by variation of the filtration coefficient and of initial blood volume (Lp,fit, Vb,fit). The linear regression between Vb,fit and blood volume determined from anthropometry (Vb,calc) was highly significant (r = 0.79, N = 30, P < 0.001). Compared to Vb,calc, Vb,fit was typically increased by 21 +/- 11%, reflecting a fluid overload at the beginning of the treatment. Lp,fit was not different from Lp,calc. Lp,fit significantly increased with blood volume excess. Due to the small but definite protein content of refilling volume, the model accounts for increased blood volume recovery and occasional overshoot of blood and plasma volumes following ultrafiltration.

Bone marrow changes following treatment of renal anemia with erythropoietin.

In 14 severely anemic patients with end-stage renal disease and chronic hemodialysis the effect of recombinant human erythropoietin (EPO) on hemopoiesis was investigated. Bone marrow biopsies were taken before and after four and 26 months of treatment with EPO to evaluate quantitative and qualitative changes of histomorphology. EPO induced normalization of maturation and an increase in cell mass of the erythropoietic line in all patients. The number of megakaryocyte also increased significantly with EPO treatment (P less than 0.01). At the time of the third bone marrow biopsy (26 months) erythropoiesis was normal. Megakaryopoiesis remained unchanged compared to the second biopsy (4 months). No cytomorphologic abnormalities or other evidence for malignant disorder could be detected in any of the patients. Hematocrit increased from a mean of 19 to 31 percent at the second evaluation (P less than 0.001). Platelet count had risen by a mean of 30,000 at four months (P less than 0.05) and slightly decreased at 26 months. These observations suggest great safety of long-term treatment with recombinant human erythropoietin, and demonstrate efficacy in correcting reduced and immature erythropoiesis in chronically hemodialyzed patients. EPO also stimulates human megakaryopoiesis.

[Clinical experiences with Wegener's granulomatosis from the nephrologic viewpoint]. / Klinische Erfahrungen mit der Wegenerschen Granulomatose aus nephrologischer Sicht.

Immunosuppressive treatment with cyclophosphamide and prednisolone has markedly improved the prognosis of Wegener's granulomatosis (WG). In patients with WG the detection of anti-neutrophil-cytoplasmic autoantibodies (ANCA or ACPA) has become an important parameter to confirm or even routinely establish the diagnosis of WG over the past few years. From 1985 to 1990 we observed and treated 12 patients (5 males and 7 females) aged 14-64 years (mean 41.1 years) with WG. In the same time span an analysis of 35 patients with rapidly progressive glomerulonephritis showed that the octiology was idiopathic in the majority of cases (54.3%), but nevertheless 8 cases (22.8%) were caused by WG. In 9 out of 10 cases the ANCA test was positive; whereas in 8 out of 10 cases we found a close correlation between the serum level of ANCA and disease activity. However, extraordinarily high serum levels (titres up to 1:2560) were recorded in one patient with WG without any clinical symptoms, whilst another patient with severe symptoms of WG showed a titre of only 1:5. 10 out of 12 patients were successfully brought to remission under cyclophosphamide-cortisone treatment. 4 out of 10 patients with renal insufficiency have been retained on the chronic haemodialysis regimen. 2 patients, aged 31 and 51 years, died within 2-5 months after the onset of clinical symptoms of WG.

Cerebral hemodynamic changes following treatment with erythropoietin.

Adverse hemorheologic effects induced by erythropoietin (EPO) treatment of renal anemia may pose a cerebrovascular risk. We therefore investigated the changes in cerebral perfusion, cerebral blood flow velocity (BFV) and neuropsychologic performance in 11 patients (mean age 37 years) receiving EPO. In response to EPO there was a significant (p less than 0.01) increase in hematocrit (35%), hemoglobin (43%) and whole-blood viscosity (50% at high and 90% at low shear rate). The initially increased blood flow velocity dropped significantly (p less than 0.05) and returned toward normal values in the middle cerebral arteries and the basilar artery (22 and 19% decrease, respectively). Global cerebral blood flow (CBF) decreased by 10% (not significant). The score of the Wechsler Adult Intelligence Scale digit symbol test improved significantly (p less than 0.01) after EPO treatment. None of the patients developed cerebrovascular symptoms or side effects. We conclude that the hematologic and rheologic changes following EPO treatment cause CBF and BFV to return toward normal and improve neuropsychologic performance in patients with end-stage renal disease.

[Special problems of nutritional therapy in chronic kidney insufficiency in the pre-dialysis stage]. / Spezielle Probleme der Ernährungstherapie bei chronischer Niereninsuffizienz in der Prädialysephase.

The main objectives of medical and nutritional management of patients with chronic renal failure are to slow down the progression of renal disease and to prevent secondary complications due to hypertension, uremic metabolic disturbances, and bone disease. The importance of nutritional measures for this purpose is increasingly recognized. In the setting of vitamin D and calcium deficiency secondary hyperparathyroidism and retention of phosphate result in renal osteodystrophy. An increase in dietary calcium and avoidance of foods rich in phosphate are important. In some patients supplementation of vitamin D3 may be necessary while calcium homeostasis is monitored during follow up. The dietary protein content can influence the severity of the uremic state. Normal or increased consumption of protein may accelerate the progression of renal disease due to the accumulation of nitrogenous products. In addition, uremia itself may cause loss of appetite and thus accumulation of endogenous nitrogen compounds as a result of protein catabolism. Protein restriction under such circumstances may cause malnutrition and an associated increase in morbidity and mortality. Thus, dietary management must consist of individually designed restriction of total protein intake with ingestion of high value protein. This allows balanced nitrogen metabolism with a reduction in circulating uremic toxins.

[Continuous measurement of blood volume changes in hemodialysis using an ultrasound method]. / Kontinuierliche Messung von Blutvolumenänderungen während der Hämodialyse mit einer Ultraschallmethode.

Haemodialysis treatment comprises the removal of surplus body water, mainly by ultrafiltration. Frequent complications, such as hypotension, are believed to be related to an imbalance between blood volume reduction, based upon ultrafiltration, and vascular refilling. The control of fluid balance can be achieved by the measurement of blood volume changes. A new method of determining total blood protein concentration by ultrasonic means facilitates continuous monitoring of blood volume changes during haemodialysis. Blood volume monitoring was undertaken during 38 haemodialysis treatments (19 patients) in order to achieve a better adjustment of the patient's estimated dry weight. The relative change in blood volume was registered in 11 patients who were first ultrafiltrated to their estimated dry weight. In a following session the ultrafiltration was increased by 10%. The relative change in blood volume, normalized to the change in total body water, increased significantly from 1.16 +/- 1.11% (normal ultrafiltration) to 1.67 +/- 0.8% (normal ultrafiltration + 10%) (p less than 0.05). Thus, normalized blood volume reduction may serve as an approximation to adjust the patient's dry weight.

Methods in clinical hemorheology: the continuous measurement of arterial blood density and blood sound speed in man.

Both blood density and sound speed are closely related to total protein concentration in blood and, as a consequence, to rheologically important parameters of blood. Two methods that permit continuous measurement of these properties, the mechanical oscillator technique and the new ultrasonic technique, were used for measuring blood protein concentration over a continuous period of time in a group of hemodialysis patients and in volunteers. It was seen that the concentration of the components of blood varies considerably. This variability is related to transport phenomena within as well as to the flow of masses across the cardiovascular compartment. From the continuous measurement of concentrations during hemodialysis treatment, relative changes in blood volume can be recorded in order to control the fluid balance of the patient. Rapid fluctuations at the macroscopic scale with periods of 5 to 30 seconds are due to heterogeneities at the microscopic scale and to the particular rheological behaviour of the red blood cells at the level of the capillaries and the small blood vessels. The amplitude of rapid oscillations increased up to 1.2% in terms of hematocrit values when there was rhythmic, spontaneous breathing at various frequencies. The measurement of concentrations at an accessible measuring site may be used to investigate the rheology of blood in the human microvasculature.

Quantitative static and dynamic renal scintigraphy with diuresis stimulation in renovascular hypertension.

The results of computer-assisted static and dynamic renal scintigraphy in 57 patients with renovascular hypertension (RVH) and 23 patients with essential hypertension (EH) are presented. The following parameters were quantified: renal size (RS), count density (CD), relative unilateral renal clearance (RRC), mean parenchymal transit time (PTT), difference of time-to-peak of activity (tmaxd) to stenosed minus non-stenosed side, effect of frusemide (FE) and renal parenchymal radionuclide retention (RI). Among 57 stenosed renal arteries we detected 54 (true-positive cases) and missed three (false-negative cases); among 23 patients with EH and no significant haemodynamic renal artery stenosis, we found 21 cases correctly negative and two patients falsely positive. These data yielded a sensitivity of 95% and a specificity of 92%. The quantification of renal radionuclide studies in renal artery stenoses minimizes false-positive results and increases their specificity. This study shows that, because of its sensitivity, quantitative renal scintigraphy reliably allows the assessment of the functional haemodynamic effects of a renovascular lesion (significant stenosis) in the diagnostic work-up and during follow-up after surgical reconstruction or percutaneous transluminal angioplasty (PTA). The evaluation of renal function is in general greatly supported by the quantitative parameters, yet particularly after medication with converting enzyme inhibitors and after intervention.

Relationship between generation and plasma concentration of anorganic phosphorus. In vivo studies on dialysis patients and in vitro studies on erythrocytes.

The plasma concentration of inorganic phosphorus (Pi) was determined before, during and after hemodialysis in 28 patients with chronic renal failure. Pi plasma concentration decreased rapidly when hemodialysis was started but did not fall below normal levels during continued dialysis. These changes of Pi concentration were fitted to a model of Pi kinetics in which Pi delivery to plasma is a nonlinear function of the extracellular Pi concentration. In separate in vitro studies, erythrocytes from six subjects with normal renal function and from 14 patients with chronic renal failure were incubated in homologous plasma with various amounts of Pi added. All other factors known to affect the Pi shift between intra- and extracellular fluid compartments (pH, calcium concentration) were kept constant. The relation between Pi concentration in plasma used for incubation and in red cells after 1h incubation suggested a mechanism in which a high plasma concentration results in movement of Pi into red cells where Pi is stored most probably in glucose esters. At low Pi plasma concentration Pi is delivered to plasma at a rate which cannot be explained solely by passive movement of intracellular Pi to plasma but requires additional generation from intracellular storage forms. The generation and delivery of Pi in patients and in their erythrocytes indicate a simple cell-mediated Pi homeostasis counter-acting abnormal fluctuations of plasma Pi.

[Results of a multicenter study of the early detection of glomerulonephritis. 1]. / Ergebnisse einer multizentrischen Studie zur Früherkennung der Glomerulonephritis. 1. Mitteilung.

In the framework of a multicentric retrospective study between selected clinics of the Republic Austria and the GDR anamnestic, clinical and paraclinical data were investigated in their valency for the early recognition of glomerulonephritis. Data of 583 patients were evaluated. Hereby it was shown that independent of the size of excretion and the reproducibility the findings "proteinuria" are of particular significance for the early recognition. The serological investigations usually performed within the diagnostic of glomerulonephritis proved as insignificant for the early recognition. Since the establishing of an exact diagnosis is up to now possible only with the help of invasive methods, a call on research is made to develop reliable, non-invasive diagnostic methods.

[Cyclosporin A as a diabetogenic cofactor]. / Cyclosporin A als diabetogener Kofaktor.

Two kidney transplanted patients are reported, who developed an insulin dependent diabetes mellitus after crossing therapeutic Cyclosporine A levels. After stabilisation of the Cyclosporine A levels the insulin dependent diabetes mellitus was completely reversible. The results are indicating Cyclosporine A as the insulin dependent diabetes mellitus initiator.

[Successful treatment of autoimmune hemolytic anemia with cyclosporin A]. / Erfolgreiche Behandlung einer autoimmunhämolytischen Anämie mit Cyclosporin A.

A sixty-year-old patient suffering from an idiopathic immunohemolytic anemia was treated by 3 plasma exchanges (with 31 exchange-volume) and following by Ciclosporin A (3 mg/kg body weight) after the monotherapy of prednisone has been unsuccessful. Ciclosporin A promptly effected a continuous remission of the autoimmune hemolysis. The mode of action of Ciclosporin A in immunhemolytic anemia depending on incomplete warm-auto-antibodies is discussed.

[Acute kidney failure]. / Akute Niereninsuffizienz.

The etiology of acute renal failure is quite complex, in contradistinction to the monotonous appearance of the corresponding renal pathomorphology (tubular necrosis, intracapillary coagulation). A basic prerequisite for the successful prevention of acute renal failure is the knowledge of the responsible atiopathogenetic factors and their early recognition. Once kidney damage has occurred, therapeutic measures shift to concentrate on the symptomatic treatment of renal failure and the prevention of accompanying complications such as a hemorrhagic tendency, susceptibility to infections, hyperkalemia, hyperhydration, catabolism etc. In addition to the proper choice of the detoxification procedure (hemodialysis, hemofiltration, peritoneal dialysis, continuous a.v. hemofiltration) precise fluid and electrolyte balance, optimal nutrition, and the adjustment of drug dosages to the degree of renal insufficiency all play an important rule. The therapeutic principles and the differential therapy of the various detoxification procedures are discussed on the basis of concrete recommendations.