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Anemia is a constant complication of uremia. As it has been suggested that uremic toxins (middle molecules) play an important role in the mechanism of anemia, we studied the activities of three heme-synthesizing enzymes: δ-aminolevulinic acid dehydratase, porphobilinogen deaminase and ferrochelatase. In 26 patients on regular dialysis therapy, all three enzymes had significantly lower values than in normal control subjects. From our results, it can be assumed that the decreased heme biosynthesis in chronic uremic patients might be caused by a lack of erythropoietin or by uremic toxins inhibiting erythropoietin and/or heme-synthesizing enzymes.

Background. Posttransplant hemolytic uremic syndrome (pHUS) is a rare but severe disorder that confers a poor prognosis on an allograft due to thrombotic microangiopathy. Immunosuppression with cyclosporine (CsA) is implicated as a significant risk factor for the development of pHUS. In early reports, it was hypothesized that immunosuppression with FK506 (tacrolimus) would avoid the development of pHUS. However, this initially supposed beneficial effect remains controversial, because pHUS associated with tacrolimus therapy has been published in some later case reports. This article aims to further evaluate FK506 with respect to the development and resolution of pHUS. Methods. We describe the course of seven adult kidney graft recipients with pHUS, treated with FK506 either as initial immunosuppression for retransplantation or after discontinuation of CsA for resolution of pHUS. Work-up for pHUS was initiated when certain clinical features, such as hemolytic anemia, thrombocytopenia, and deterioration of graft function, were found. The diagnosis was confirmed by histologic examination of a renal allograft biopsy specimen (thrombotic microangiopathy). With the onset of pHUS, additional plasma exchange was performed in all patients. Results. Two patients suffered from end-stage renal disease due to primary HUS and had a history of recurrent pHUS in previous renal transplants. In both patients, the attempt to regraft was only made because of the early optimistic reports using FK506. Despite initial FK506 therapy, both recipients developed pHUS again, leading to loss of graft function. Two additional kidney graft recipients with primary renal failure other than HUS also received FK506 as initial immunosuppression. One of them (loss of the first kidney graft due to CsAinduced pHUS) was successfully treated with FK506 for his second renal transplant. The other recipient, a patient in whom de novo pHUS had occurred in the first graft despite initial therapy with FK506, was treated with CsA for his second graft and again developed pHUS. The latter process, however, could be reversed by a switch to steroids and azathioprine. In all three patients regrafted for reasons other than pHUS, development of de novo pHUS was treated by CsA withdrawal and a switch to FK506; this approach was effective in two patients. Conclusion. Our results demonstrate that three of seven renal allograft recipients benefited from FK506 therapy for prevention or resolution of pHUS. Treatment or prophylaxis with FK506 can be considered advantageous in some patients with de novo pHUS, but FK506 fails to prevent recurrent pHUS in patients with primary HUS.

With the on-line preparation of substitution fluid, an easy-to-operate and cost-effective alter-native to conventional hemodiafiltration (HDF) has been realized. The continuous filtration of dialysis fluid, furthermore, allows high volumes of exchange. Microbial contamination and subsequently endotoxins, however, may be present in dialysis fluid, and thus the microbiological safety has become a pivotal issue.In this clinical study we evaluated the safety of the Fresenius Medical Care on-line HDF system which is based on a two-stage filtration of dialysis fluid with upstream DIASAFE® and downstream on-line HDF filter. During the three-month study period we failed to detect germs or endotoxins in the substitution fluid. Augmented plasma interleukin-1β (IL-1β) and tumor necrosis factor α (TNFα) concentrations were found neither during the intradialytic period nor when pre-session values at study begin and study end were compared. In addition, changes in the anti-endotoxin core antibody levels and soluble CD14 (sCD14) concentration, or pyrogenic episodes were not observed.On-line HDF with DIASAFE® and on-line HDF filter thus represents a safe treatment modality by effectively depleting dialysis fluid of cytokine-inducing substances.

This 1-year double-blind, placebo-controlled, multicenter study evaluated the long-term safety and efficacy of cinacalcet for the treatment of secondary hyperparathyroidism in patients receiving hemodialysis.Patients were randomly assigned in a 1:1 ratio to cinacalcet or control treatment groups. The initial dose of cinacalcet (or matching placebo) was 30 mg. Doses were titrated every 3 or 4 weeks based on the intact parathyroid hormone (iPTH) response and safety profile. Sequential doses included 30, 60, 90, 120 and 180 mg/d. Phosphate binders and vitamin D sterols were adjusted per protocol as needed to control levels of calcium and phosphorus. Efficacy and safety were compared between treatment groups among patients who completed the study (52 total weeks of treatment). Reasons for withdrawal are presented for patients who did not complete the study.A total of 210 patients completed 52 weeks of double-blinded treatment with cinacalcet (n = 99) or placebo (n = 111). Over the last 6 months of the study, a greater proportion of patients in the cinacalcet group than the control group achieved an iPTH levelor = 250 pg/ml (61.6 vs. 9.9%, p0.001) or aor = 30% decrease in iPTH from baseline (81.8 vs. 21.6%, p0.001). Mean iPTH levels decreased by -47.8% in the cinacalcet group and increased by +12.9% in the control group. Mean percentage changes in other laboratory values in the cinacalcet and control groups included the following: serum calcium -6.5 vs. +0.9% (p0.001), serum phosphorus -3.6 vs. -1.1% (p = 0.465), and Ca x P -9.9 vs. -0.3% (p = 0.006). The most commonly reported adverse events related to study drug by the investigators included nausea (13% cinacalcet, 5% control), investigator-reported hypocalcemia (11% cinacalcet, 1% control), vomiting (9% cinacalcet, 2% control), dyspepsia (5% cinacalcet, 4% control), and diarrhea (5% cinacalcet, 2% control).Treatment with cinacalcet is a safe and effective therapy for long-term control of secondary hyperparathyroidism. 1-year therapy with cinacalcet was associated with sustained, clinically significant reductions in calcium, Ca x P and iPTH which allowed a greater percentage of patients to achieve NKF-KDOQI target goals for PTH and Ca x P.

With the on-line preparation of substitution fluid, an easy-to-operate and cost-effective alternative to conventional hemodiafiltration (HDF) has been realized. The continuous filtration of dialysis fluid, furthermore, allows high volumes of exchange. Microbial contamination and subsequently endotoxins, however, may be present in dialysis fluid, and thus the microbiological safety has become a pivotal issue. In this clinical study we evaluated the safety of the Fresenius Medical Care on-line HDF system which is based on a two-stage filtration of dialysis fluid with upstream DIASAFE and downstream on-line HDF filter. During the three-month study period we failed to detect germs or endotoxins in the substitution fluid. Augmented plasma interleukin-1beta (IL-1beta) and tumor necrosis factor alpha (TNFalpha) concentrations were found neither during the intradialytic period nor when pre-session values at study begin and study end were compared. In addition, changes in the anti-endotoxin core antibody levels and soluble CD14 (sCD14) concentration, or pyrogenic episodes were not observed. On-line HDF with DIASAFE and on-line HDF filter thus represents a safe treatment modality by effectively depleting dialysis fluid of cytokine-inducing substances.

Angiotensin-converting enzyme (ACE) inhibitors are known to reduce blood pressure and proteinuria in a variety of different glomerular diseases. Nonetheless, a marked interindividual difference in the efficacy of these agents exists. The activity of the ACE and therefore of the renin-angiotensin-aldosterone system (RAAS) has been shown to be under genetic influence. Patients with a deletion genotype at the intron 16 of the ACE gene have been shown to exhibit higher activity of plasmatic ACE when compared to patients with the insertion genotype. We therefore studied prospectively the hemodynamic and antiproteinuric effect of a 6-month therapy with enalapril in patients with biopsy-proven proteinuric glomerular diseases and the DD (n = 10) and ID/II (n = 26) genotype. Although patients with the DD genotype received a slightly higher dose of enalapril, blood pressure and proteinuria did not change significantly. However, both were significantly reduced in the II/ID group after 10 weeks and 6 months of therapy. Creatinine clearance decreased steadily in DD patients. In II/ID patients, creatinine clearance was reduced significantly after 10 weeks of therapy but increased again thereafter and the value at 6 months was again comparable to the one obtained in the DD patients. We conclude from our study that the ACE genotype influences the blood pressure-lowering and antiproteinuric effect of enalapril in patients with proteinuric glomerular disease.

The kidney is the most important organ for regulating the ion composition of the extracellular space [50, 51, 128]. Filtration of primary urine from the plasma takes place via the glomeruli. In the proximal tubule and the pars recta over 70% of the filtered salts and water are reabsorbed, while glucose, amino acids and bicarbonate are almost completely absorbed. In the loop of Henle further reabsorption of water and sodium chloride takes place and, at the transition to the pars convoluta, sodium chloride is again reabsorbed (Fig. 25). The reabsorption of sodium chloride, and indirectly of water, in the distal tubule is regulated by aldosterone. Open image in new window Fig. 25. Absorption and secretion of electrolytes and water in the nephron. Modified from [63]. 1 Glomerulus, 2 Proximal tubule, 3 Pars recta, 4 Loop of Henle, 5 Pars convoluta, 6 Distal tubule

Water accounts for about 60% of the body weight (BW); two thirds of total water are attributed to the intracellular space (ICS) and one third is located in the extracellular space (ECS). The two spaces are separated from one another by the cell membrane. The extracellular space is subdivided into the interstitial space, ISS, and intravascular space, IVS. The ISS contains about 75% and the IVS about 25% of the water of the ECS. The border between these two spaces is the capillary wall (Fig. 1). Open image in new window Fig. 1. Fluid spaces and fluid distribution in the body compartments (data as % of body weight). ECS: Extracellular space. ICS: Intracellular space. ISS: Interstitial space. IVS: Intravascular space Open image in new window Fig. 2. Concentration of anions and cations in the body compartments. Data in mmol/l. Proteins and organic anions have not been taken into account

Normale Nieren arbeiten kontinuierlich, ohne Unterbrechung 24 h pro Tag. In Nachahmung dieser physiologischen Gegebenheiten wurden daher Blutreinigungsverfahren entwickelt, die im Gegensatz zu den herkommlichen intermittierden Nierenersatztherapien ebenfalls kontinuierlich entgiften. Die Vorteile kontinuierlicher Verfahren liegen u.a. in der Erzielung eines "steady state", sowohl im Hydratationszustand als auch in der Zusammensetzung der Korperflussigkeiten. Rapide Volumenschwankungen und Schwankungen in der chemischen Zusammensetzung und Osmolaritat der extrazellularen Flussigkeit, wie sie bei der intermittierenden Hamodialyse auftreten, werden dadurch vermieden. Nebenwirkungen der intermittierenden Hamodialyse, v.a. Kreislaufinstabilitat, pulmonale und zerebrale Komplikationen, werden dadurch minimiert. Konvektive Methoden in der Nierenersatztherapie (wie z.B. Hamofiltration) wurden erst nach den diffusiven Verfahren (z.B. Hamodialyse) eingefuhrt. Zum erstenmal beschrieb Henderson [4] ein rein konvektives Verfahren, das er damals allerdings noch ,,Diafiltration" nannte. Silverstein fuhrte 1974 eine Ultrafiltrationstechnik fur Patienten mit Uberwasserung ein [9]. Wir beschrieben 1976 eine Methode zur Verwendung der Kapillarniere in der Odemtherapie [13]. Auch in der Originalarbeit von Kramer 1977, in der die CA VH, die kontinuierliche arteriovenose Hamofiltration, erstmals beschrieben wurde, findet diese Methode zunachst nur bei der Behandlung der Uberwasserung Einsatz [6]. Erst in der Folge wurde die Einsatzmoglichkeit dieser Methode auch als Blutreinigungsverfahren offensichtlich [7]. Die Einfachheit dieser Methode, kombiniert mit den beim Einsatz im Intensivbereich vorhandenen Vorteilen gegenuber der intermittierenden Dialyse, hat die kontinuierlichen Verfahren zum neuen "golden standard" in der Behandlung des ANV (v.a. im Rahmen des Multiorganversagens) gemacht.

The concentration of atrial natriuretic peptide (hANP) in plasma from venous blood of healthy subjects was measured by radioimmunoassay. hANP from 5 mL of EDTA-treated plasma was adsorbed onto Sep-Pak C18 cartridges, which were eluted with methanol/trifluoroacetic acid (5 mL/L), 90/10 by volume. The eluates were concentrated by evaporation under nitrogen and lyophilized. After redissolving the samples in 0.5 mL of sodium phosphate buffer, we incubated 100-microL aliquots with anti-alpha-hANP for 24 h, then added 125I-labeled alpha-hANP tracer; 24 h later, we separated the bound and free fraction by adding an antibody/polyethylene glycol complex as the second antibody. The sensitivity of the assay was 2 pg per tube (B0-3 SEM). In the useful range of B = 15 to 85% of B0, CVs for within-run and between-run precision did not exceed 8 and 12%, respectively. The 50% intercept of the standard curve was at 12 pg per tube. hANP concentrations for 36 healthy adults ranged from 8 to 68 ng/L.

Uremia is accompanied by a variety of “true” and “laboratory” endocrine disorders, due in part to impaired degradation of hormones because of failing kidney function and in part to the interference of the uremic environment with extrarenal degradation or synthesis and secretion of certain hormones. “True” endocrine disorders, like hyperparathyroidism or hypogonadism, that are associated with renal insufficiency are in contrast with “laboratory” endocrine disorders in uremia, where pathological serum hormone levels lack clearcut clinical evidence for dysfunction of the respective endocrine organ (e.g. thyroid gland). This lack of a direct cause and effect relationship in uremia may be due to the fact that immunoassayable hormone levels may include cross reacting components without biological activity in uremia and to the fact that the uremic environment may alter hormonal effects on target organs.

Recombinant human erythropoietin (r-HuEPO) has recently become available for clinical trial and has been used for the first time in Austria for the treatment of transfusion dependent patients on chronic haemodialysis. Inclusion criteria into the study were baseline haemoglobin levels of less than or equal to 6 g/dl and transfusion requirements of greater than or equal to 1 unit of blood per month. r-HuEPO (CILAG/AMGEN/ORTHO) was administered intravenously 3 times weekly at the end of dialysis. The initial dose was 100 U/kg body weight at each administration and was increased by 25 U/kg if Hb levels failed to increase by greater than 5% of baseline at intervals of 3 weeks. All 9 patients studied showed an increase in Hb values to the desired value at least greater than or equal to 10 g/dl within 6 to 16 weeks and none of the patients required further blood transfusions. All patients reported subjective improvement of life quality and markedly increased working ability. Apart from minor episodes of bone pain and subfebrile temperatures after r-HuEPO administration no major side effects were noted. These preliminary results show that r-HuEPO (CILAG/AMGEN/ORTHO) is a safe and effective form of therapy for renal anaemia and one which opens new horizons in the management of patients on chronic haemodialysis.

Intrapulmonary percussion with a high-frequency jet system is a new method in the treatment of respiratory impairment. It imitates the conventional percussion massage of the thorax by introducing high-frequency gas oscillations (300 impulses per minute) into the tracheobronchial system. In 14 patients with abnormal alveolo-arterial oxygen differences due to bronchial mucostasis ventilation was satisfactorily improved by its application.

Maximal tubular phosphate reabsorption capacity corrected for changes in glomerular filtration rate (TmP/GFR) was taken as a measure of renal phosphate handling in patients with good and stable functioning kidney allografts. TmP/GFR values were within the normal range in only one-fifth of the patients. Eighty per cent had an abnormally low renal phosphate threshold concentration. Persistent hyperparathyroidism was the causative factor of this diminished tubular reabsorption in less than half of these patients, the majority of them showing an iPTH independent phosphate leak. Although glucocorticoids, azathioprine and tubular damage of the graft in the perioperative phase may contribute to this iPTH independent phosphate wasting, no single causative factor could be identified. Cases with hypophosphataemia should be treated in order to avoid symptoms of phosphate depletion. Active Vitamin D metabolites would be the therapy of choice by suppressing the parathyroid glands ("chemical PTX") and by directly enhancing tubular phosphate reabsorption. In persistent hyperpathyroidism with hypercalcaemia, surgical parathyroidectomy must be considered. Therapy with phosphate salts is only symptomatic and should be used only as an adjunct.

Hemodialysis therapy is the most commonly used renal replacement therapy despite the development of alternative detoxification procedures. As in any therapy hemodialysis treatment shows side effects. These regularly appearing intradialytic complications are essentially responsible for the morbidity of the dialysis patient. Studies were undertaken to clarify the pathomechanisms of the dialysis hypoxemia and dialysis hypotonia. Intradialytic variations of carbohydrate and protein metabolism and of the cellular blood components were analyzed. The exact knowledge of the pathomechanisms of these side-effects should lead to technical improvement in dialysate composition. With this knowledge a more effective treatment and a better prophylaxis of these intradialytic side effects should be possible.

Four adult recipients of cadaveric renal homografts acquired Pneumocystis carinii infections from which they subsequently died. The disease in adults under immunosuppressive therapy runs a course different from the disease observed in newborns. The clinical course is rapidly progressive and early diagnosis by means of aggressive diagnostic procedures is mandatory. To prevent a fatal outcome, treatment even on suspicion is suggested. Epidemiologically, a person-to-person spread seems possible and isolation of the patient is necessary.

Uremia is accompanied by a variety of "true" and "laboratory" endocrine disorders, due in part to impaired degradation of hormones because of failing kidney function and in part to the interference of the uremic environment with extrarenal degradation or synthesis and secretion of certain hormones. "True" endocrine disorders, like hyperparathyroidism or hypogonadism, that are associated with renal insufficiency are in contrast with "laboratory" endocrine disorders in uremia, where pathological serum hormone levels lack clearcut clinical evidence for dysfunction of the respective endocrine organ (e.g. thyroid gland). This lack of a direct cause and effect relationship in uremia may be due to the fact that immunoassayable hormone levels may include cross reacting components without biological activity in uremia and to the fact that the uremic environment may alter hormonal effects on target organs. This review tries to give a survey of the big amount of available clinical and laboratory data for uremia induced changes in the following hormones: growth hormone and somatomedins, prolactin, cortisol and adrenocorticotrope hormone, the gonadal and thyroid function as well as parathyroid hormone action. The knowledge of these uremia-induced changes should facilitate the clinician the diagnosis of an additional primary endocrine ailment in a uremic patient and should, on the other hand, spare these patients unnecessary treatment for a suspected endocrine disorder.

In eight chronically haemodialysed patients a significant increase of circulating platelet aggregates (method of Wu and Hoak) was observed immediately after starting haemodialysis. The number of aggregates decreased at the end of haemodialysis reaching the starting values after 360 min. The platelet interaction with the dialysis membrane surface might cause this phenomenon. Anticoagulation with heparin alone was insufficient in preventing aggregate formation during haemodialysis.

Reduced carbon monoxide diffusing capacity of the lung (DLCO) is reported in patients with impaired renal function. Since DLCO also depends on the pulmonary capillary blood volume the role of renal anaemia was evaluated. Measurements were carried out in 43 azotaemic patients [serum creatinine (SKr) 1.5 to 14.0 mg/100 ml], without evidence of cardiovascular or pulmonary complications of uraemia, of SKr, haemoglobin concentration (Hb) and steady state DLCO. In the case of DLCO values allowance was made for body surface area and thoracic gas volume. The relation was studied of the corrected DLCO to SKr and to Hb. There was a higher statistical correlation between DLCO and Hb than between DLCO and SKr. After additional correction of DLCO for Hb, no correlation to SKr was found. It is concluded that the reduction in DLCO in uraemia is due largely to a low Hb and, hence, to renal anaemia rather than to uraemic damage of interstitial lung tissue.

Abnormalities of thyroid and pituitary function are well recognized in patients with end-stage renal failure. We have investigated the influence of varying degrees of renal insufficiency on serum thyroid (total thyroxine, TT4; total 3,5,3′-triiodothyronine, TT3, and 3′,5′,3′-triiodothyronine, reverse T3) and pituitary (thyrotrophin, TSH; growth hormone, GH; prolactin, PRL) hormone levels before and after 200 μg thyrotrophin releasing hormone (TRH) iv administration. Patients with mild renal insufficiency (= group 1, plasma creatinine (Cr) > 1.3 mg% but < 3.0 mg%) had normal basal and TRH-stimulated hormone concentrations. In patients at a more advanced stage of the disease (= group 2; Cr > 3.0 mg % but < 7.0 mg %) basal hormone concentrations were also normal. In contrast to the normal group, where no GH reaction to TRH could be detected, GH serum concentrations increased in these patients after TRH. The TT3 and PRL response to TRH remained normal. The TSH reaction to TRH was blunted in four, normal in two and exaggerated in one patient. Patients with end-stage renal failure (= group 3; Cr > 7.0 mg%) had significantly decreased basal TT3 concentrations but a normal TT3 response to TRH. Basal TT4, TT3 and TSH concentrations were normal. The TSH reaction was blunted in four and normal in three patients. The mean basal GH was elevated, albeit not significantly different from the control mean value. The GH increase after TRH was even more pronounced than in group 2. Basal PRL concentrations were significantly increased, but maximal differences between basal and TRH-stimulated concentrations were not significantly different from control. Our data suggest that changes in the pituitary and hypothalamic control of GH are an early consequence of renal insufficiency. Alterations in thyroid function occur simultaneously on the pituitary – hypothalamic and peripheral level at a more advanced stage of the disease. PRL basal levels increase with decreasing renal function. In contrast to other studies we could not observe any significant influence of uraemia on the TRH-stimulated PRL reserve of the pituitary.

1 alpha-hydroxycholecalciferol was tried as a therapy for renal phosphate wasting in kidney allograft recipients with normal parathyroid gland activity. During a 3-week period of treatment we observed a significant rise in renal phosphate threshold concentrations and plasma phosphate levels paralleled by a significant decrease in serum immunoreactive parathyroid hormone levels and a significant increase in intestinal calcium absorption. It is suggested that 1 alpha-hydroxycholecalciferol acts on renal phosphate handling in a dual fashion: one is by suppression of parathyroid hormone and the other by restoration of 1,25-dihydroxycholecalciferol levels to an appropriate level.

The methods of continuous hemofiltration therapy are described. The various forms of blood access are discussed, especially the pumpdriven venovenous form of hemofiltration utilizing a double lumen catheter in the superior caval vein is demonstrated as an alternative to the spontaneous arteriovenous method. The own experiences in over 140 patients with renal, cardial and pulmonal indications are summarized.

In earlier studies we have shown that partial correction of anemia by recombinant human erythropoietin (r-HuEPO) already after 12 weeks results in a significant increase of exercise capacity in patients on chronic hemodialysis. As causative effect increased oxygen availability with improved oxygen delivery to the tissues was assumed. To elucidate the long-term effects of a partial correction of anemia with r-HuEPO on exercise capacity, oxygen uptake at maximum exercise and at the anaerobic threshold was measured by repetitive spiroergometry. Measurements were done before, 3 months and 6 months after initiation of r-HuEPO therapy. The results are summarized below: (table; see text) Our results show that a long-term improvement of peripheral oxygen availability leads to a further increase of anaerobic threshold in patients on chronic hemodialysis even without a further increase of hemoglobin levels and without exercise training. It appears that elimination of the chronic hypoxic condition results in a restoration of previously diminished mitochondrial enzymes in muscle, particularly for aerobic glycolysis. Besides acute improvement of aerobic and anaerobic exercise capacity, the long-term administration of r-HuEPO with its increased anaerobic threshold enhances the patients' everyday life working capacity.

6 fluid overloaded patients with congestive heart failure, NYHA classification IV, resistant to drug therapy, were treated by pump driven venovenous hemofiltration. The sympathetic nervous system measured by plasma norepinephrine concentration was stimulated in all patients. 4 of 6 patients had a markedly enhanced plasma renin activity. Between 7 and 20 l of fluid were removed by hemofiltration. The expected increase of plasma norepinephrine did not occur in 4 out of 6 patients. The improvement of cardiac pump function by hemofiltration could be an explanation for this apparent paradoxical regulation. Patients who had almost a normal plasma renin activity prior to hemofiltration showed a marked increase after the procedure. In patients with extremely high levels of plasma renin activity we noted a decrease after hemofiltration. Almost in every patient with a serum sodium concentration lower or equal 132 mmol/l the plasma renin activity was markedly elevated. Patients with normal serum sodium concentrations exhibited only slightly elevated plasma renin activity. Therefore, a hyponatremia in patients with heart failure can be used as a marker for high plasma renin activity. All patients had a significant improvement of the clinical state after hemofiltration. 3 patients, however, showed deterioration within a few weeks, due to the severity of the disease. Their plasma norepinephrine levels remained high or had a tendency to increase.

26 hypertensive patients groupded according to the severity-index and the WHO-index were treated with pindolol (monotherapy, 15 mg daily). The response of blood pressure depression was statistically significant, although not always sufficient when judged by clinical parameters. Plasma renin activity responded variably to the treatment in different patients and different groups. In 18 patients a statistically significant increase of serum potassium could be observed. No major side effects of therapy were encountered.

The presence of antibodies against ethylene oxide, which is used for sterilization of dialyzers, was evaluated in 52 hemodialysis patients (30 male, 22 female). The aim of the prospective study was to evaluate a possible correlation of these antibodies with hypersensitivity reactions during hemodialysis. By means of a radio-allergo-sorbent-test (RAST) only 3.9% (2 patients) were detected to have ethylene oxide antibodies. There was no significant correlation between antibodies on the one hand, and symptoms, eosinophilia and IgE-elevation on the other hand. We could not find ETO-induced hypersensitivity reactions in our study population. Thorough rinsing and sufficient storage time of the dialyzers might be the reasons for these findings.

The effects of desferrioxamine administration of aluminium kinetics during haemodialysis were studied. Desferrioxamine leads to an increase of plasma aluminium levels in patients on chronic haemodialysis which could be attributed to mobilisation of tissue aluminium. Furthermore the ultrafiltrable function of plasma aluminium was greatly enhanced thus increasing the effective concentration gradient of aluminium between plasma and dialysate. Desferrioxamine therefore leads to increased aluminium removal during haemodialysis and should be considered in the therapy of aluminium toxicity syndromes.

The use of urea kinetics as basis for optimization and individualization of renal replacement therapy has become quite popular over the last decade. The rationale underlying the use of blood urea nitrogen for monitoring or targeting dialysis therapy is based on the report of an American multicentre cooperative dialysis study showing that blood urea nitrogen concentrations are closely correlated to the occurrence of morbidity and complications in dialysis patients. In order to further optimize the accuracy of dialysis prescription we have developed a new algorithm for estimation of the dialysis time needed to reach a certain blood urea nitrogen concentration, which--in contrast to all methods employed so far--enables accurate calculation of ultrafiltration during haemodialysis and of weight changes in the interdialytic period.

In order to elucidate the pathogenesis of haemodialysis related hypoxaemia, lung function studies, measurements of intra-thoracic fluid changes, leucocytes and complement activity were made in 12 patients during a routine six hours dialysis using cellulose membranes. Coincidently with the fall in arterial oxygen tension, lung function was significantly impaired, paralleled by a decrease in transthoracic impedance, leucopenia and a decrease in plasma complement activity. It therefore is suggested that blood membrane interaction leads to complement-mediated pulmonary leucostasis evoking mild pulmonary oedema with impaired oxygen diffusion, resulting in hypoxaemia.

In acute and chronic kidney transplant rejection renal cortical and medullary tissue samples were examined for their prostacyclin (PGI2) generation by bioassay and compared with normal tissue. In acute rejection PGI2 formation was significantly enhanced, particularly in the cortex. In chronic rejection the PGI2 formation was comparable with control tissue. Since PGI2 is a very potent platelet aggregation inhibitor and vasodilator, it is concluded that the increase in PGI2 generation in acute rejection might be a self protecting mechanism which is, however, overwhelmed in irreversible rejection.

Methods for calculating required dialysis time to maintain certain blood urea nitrogen levels predialytically thus far have neglected the influence of ultrafiltration during hemodialysis and of weight changes in the interdialytic period. We therefore have developed a new algorithm for individual dialysis prescription based on urea kinetics which further optimizes accuracy of dialysis prescription by considering these two factors. The accuracy of this new method was proven in a prospective follow-up of 3 patients during some 9 consecutive hemodialysis session. It was found that there was a very close relation between the measured and the predicted values of blood urea nitrogen, the difference being only due to variations in dietary protein intake as the patients were kept on liberal food intake. The new algorithm is easily implemented into a pocket calculator and thus can be used under arbitrary dialysis conditions.

In this collaborative study 9 cases of intractable ascites in chronic hemodialysis patients are evaluated. Six patients died within 14, two more within 18 months after onset of ascites. Possible causes of the pathogenesis (repeated fluid overload, hydrostatic and oncotic pressure flux forces, alteration of membrane permeability) are discussed. Renal homograft transplantation seems to be the only successful treatment.

A study was carried out in 25 patients on chronic intermittent haemodialysis on the effect of increasing the dialysate calcium concentration from 1.5 to 1.75 mMol/l on calcium and phosphorus metabolism. In 16 patients the increase in the dialysate calcium resulted in a sufficiently large increase in the plasma Ca level to suppress the parathyroid glands. The calcium influx during dialysis in these patients was sufficient to abolish the effects of diminished calcium absorption from the intestine due to loss of endocrine renal function. The remaining 9 patients showed no suppression of parathyroid gland activity and could be separated into two different groups, one requiring calcium supplementation and the other group manifesting signs of autonomic hyperparathyroidism. The five patients showing a higher calcium requirement were started on active vitamin D metabolites. In the remaining 4 patients parathyroidectomy will probably be inevitable if progression of the clinical manifestations of hyperparathyroidism occurs. Close control of plasma phosphorus levels is mandatory to avoid an increase in the calcium phosphate product or the danger of hypophosphataemic osteomalacia.

Spontaneous rupture of an allografted kidney is not such a rare complication of kidney transplantation. In our series 5.2% of the transplanted kidneys ruptured spontaneously. The condition is an acute emergency characterized by the triad, acute abdomen, swelling in the region of the transplant and haemorrhagic shock. The aetiology of transplant rupture seems to be multifactorial, but the superimposition of an acute rejection episode on ischaemic tubular damage with acute renal failure was found to be the most important combination of events leading to transplant rupture in our patients. Exceptionally precise immunological monitoring in the early phases following transplantation and early aggressive therapy of an acute rejection crisis associated with acute renal failure should prevent allograft rupture.

During the past 2 years 7 children received kidneys from cadaveric donors. 2 transplants had to be removed because of irreversible chronic rejection and 1 recipient died on the 4th day after surgery. The remaining 4 recipients are doing well. In the evaluation of the results special emphasis is placed on the normalization of growth and puberty. The difficulties of psychosocial rehabilitation are stressed.

Disturbances in lipid metabolism and accelerated atherosclerosis are well-known phenomena of chronic renal insufficiency. The disturbance in lipid metabolism has been repeatedly described as secondary type IV hyperlipoproteinemia according to the classification of Fredrickson. The classification of Fredrickson, however, does not take into account the role of the alpha-lipoproteins (the HDL lipoproteins and HDL cholesterol). Hence, HDL cholesterol was determined and correlated to other routine parameters of lipid metabolism in 66 patients with different degrees of renal insufficiency. Furthermore, an intravenous fat tolerance test was performed in 14 patients with terminal renal insufficiency. Beside the well-known hypertriglyceridemia with cholesterol values near the upper limits of normal, a significant reduction in HDL cholesterol was found, showing a significant inverse correlation to plasma creatinine values. Patients with advanced or terminal renal insufficiency additionally showed a significant inverse correlation between HDL cholesterol and plasma triglycerides. The disappearance rate of intravenously administered fat emulsion (which corresponds to the clearance rate of chylomicrons and VLDL) was diminished in azotaemic patients, showing a significant inverse correlation between HDL cholesterol and disappearance rate in the intravenous FTT. Beside hypertriglyceridemia, the diminished HDL cholesterol values represent an additional risk factor for the genesis of accelerated atherosclerosis. The diminished k value demonstrates a diminished activity of lipoprotein lipase as cause of hypertriglyceridemia, whereby the positive correlation between the k value and HDL cholesterol and the inverse correlation between HDL cholesterol and triglycerides suggest a causal relationship between the decreased activity of lipoprotein lipase and diminished HDL cholesterol levels.

The therapy of secondary hyperparathyroidism in chronic renal disease has been improved by the availability of active 1-alpha-hydroxylated vitamin D derivatives. However, in cases with progressive secondary hyperparathyroidism which have not been brought under control conservatively, surgical intervention is still required. Total parathyroidectomy with autologous transplantation of parathyroid tissue in the forearm has recently been recommended as the optimum surgical approach to secondary hyperparathyroidism. Recent literature is reviewed and personal clinical experience is reported in this paper, followed by a presentation and discussion of the pathophysiology of hyperparathyroidism in chronic renal failure, various means of conservative treatment, indications for parathyroidectomy, surgical aspects and technique of cryopreservation, as well as a standardized therapeutic regimen for pre- and postoperative treatment with calcium and 1-alpha-hydroxylated vitamin D analogues.