Evidence for an increased generation of prostacyclin in the microvasculature and an impairment of the platelet alpha-granule release in chronic renal failure.

The formation of prostacyclin (PGI2) and thromboxane A2 and the release of beta-thromboglobulin (beta-TG) at the site of platelet-vessel wall interaction, i.e. in blood emerging from a standardized injury of the microvasculature made to determine bleeding time, was studied in patients with end-stage chronic renal failure undergoing regular haemodialysis and in normal subjects. In the uraemic patients, levels of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) were 1.3-fold to 6.3-fold higher than the corresponding values in the control subjects indicating an increased PGI2 formation in chronic uraemia. Formation of thromboxane B2 (TxB2) at the site of plug formation in vivo and during whole blood clotting in vitro was similar in the uraemic subjects and in the normals excluding a major defect in platelet prostaglandin metabolism in chronic renal failure. Significantly smaller amounts of beta-TG were found in blood obtained from the site of vascular injury as well as after in vitro blood clotting in patients with chronic renal failure indicating an impairment of the alpha-granule release in chronic uraemia. We therefore conclude that the haemorrhagic diathesis commonly seen in patients with chronic renal failure is--at least partially--due to an acquired defect of the platelet alpha-granule release and an increased generation of PGI2 in the microvasculature.

Prevalence of preterminal pulmonary thromboembolism among patients on maintenance hemodialysis treatment before and after introduction of recombinant erythropoietin.

The prevalence of pulmonary thromboembolism at autopsy was assessed in a retrospective study of a cohort of 185 patients undergoing maintenance hemodialysis treatment who died in the last decade. The overall frequency of thromboembolism was 12.43% in the dialysis population, which statistically was significantly less than in a control group of 8,051 nondialysis patients (21.77%; P = 0.0023). Moreover, pulmonary thromboembolism was less frequently fatal or contributing to death in the dialysis group than in the control group (P = 0.039). The prevalence of pulmonary thromboembolism in the dialysis group remained statistically unchanged over the 10-year period and was independent of a steady increase in the percentage of patients receiving recombinant erythropoietin therapy and the average hematocrit values. The occurrence of preterminal pulmonary thromboembolism was associated with a shorter period since onset of hemodialysis treatment and with infection as cause of death (P = 0. 031; P = 0.029, respectively). No statistically significant influence of the type of basic renal disease, type of dialysis anticoagulation, or dialysis access could be found. Our data suggest that, at least in the preterminal stage, the introduction of recombinant erythropoietin within the last decade had no substantial influence on the prevalence of pulmonary thromboembolism.

Progression of renal insufficiency in analgesic nephropathy: impact of continuous drug abuse.

Twenty-three patients with analgesic nephropathy and apparent cessation of drug abuse were tested for blood acetaminophen and salicylate on the occasion of routine renal control examinations. In 12 patients (mean creatinine level 2.74 +/- 1.09 mg/dl) no deterioration of renal function was noted within a 1-year observation period (Group 1). In 11 patients a significant progression of renal insufficiency was observed (mean creatinine level rose from 3.86 +/- 1.06 to 6.40 +/- 3.18 mg/dl within the same observation period; Group 2). Blood tests for acetaminophen and salicylate were positive in 2 patients of Group 1 and in 9 patients of Group 2 (chi 2 = 7.326), p less than 0.01). Our data emphasize the importance of a continuous analgesic abuse hidden from the medical staff with regard to the progression of renal insufficiency in analgesic nephropathy.

Predictive value of thallium-201-dipyridamole myocardial stress scintigraphy in chronic hemodialysis patients and transplant recipients.

The prognostic impact of thallium(Tl)-201-dipyridamole (DPM) stress and redistribution scintigraphy done in 36 patients on chronic hemodialysis (HD) and in 23 renal transplant recipients (TRs) was evaluated according to cardiovascular complications and survival in a follow-up period of six years. Though symptomatic ischemic heart disease (IHD) was present in 33% of HD patients and in 17% of TRs, 50% and 39%, respectively, had Tl-201 findings indicative of IHD. The duration of HD treatment was similar for patients with an abnormal or normal scintigraphic finding. Abnormal Tl-201 results were seen more frequently in older patients. During follow-up, 27 of 36 HD-patients died, 16 had an abnormal and 11 a normal Tl-201-DPM finding; cardiovascular complications were the cause of death in 88% and 18% of these patients, respectively. Thus the incidence of death from fatal cardiac events was 12% per year at risk for the former and 1.9% per year at risk for the latter. In TRs survival was not different for patients with an abnormal or normal Tl-201 finding (56% vs. 64%). However, fatal or nonfatal cardiovascular events were seen more frequently in patients with an abnormal Tl-201 results (78% versus 7%; p less than 0.0001). Stepwise logistic analysis and survival analysis demonstrated Tl-201-DPM stress/redistribution scintigraphy to be the only predictor for identifying patients at increased risk for cardiovascular events. In patients with abnormal Tl-201-DPM scintigraphy subsequent survival was extended for symptomatic patients as compared to asymptomatic ones )30.3 +/- 21.6 versus 22.0 +/- 17.3 months; p less than 0.008).

Diminished serum folic acid levels in renal transplant recipients.

Serum folic acid levels were determined by radioimmunoassay in 26 chronic hemodialysis patients, in 52 renal transplant recipients and in 20 healthy controls. In the dialyzed patients, the mean serum folic acid level was 3.37 +/- 1.25 ng/ml and was significantly lower than that of the controls (6.1 +/- 1.38 ng/ml, P less than 0.001). In renal transplant recipients the mean folic acid concentration was 4.09 +/- 1.58 ng/ml and was also significantly decreased (P less than 0.001). 15 (29 per cent) out of 52 renal transplant patients showed serum folic acid concentrations lower than 3.0 ng/ml. Diminished serum folic acid levels were found not only in patients shortly after surgery but also in cases with excellent graft function up to 6 years after transplantation. The highest serum folic acid level was observed in one transplant patient who had taken no azathioprine for 24 months. Macrocytosis was found in 52 per cent of our renal transplant patients. There was no significant difference between the serum folic acid levels of renal transplant recipients with (n = 27) and without (n = 25) macrocytosis; however, serum creatinine levels were significantly lower in cases revealing macrocytosis. Relative folic acid deficiency does not seem to be responsible for macrocytosis after renal transplantation. Macrocytosis was observed only in patients with good graft function treated with azathioprine. Serum vitamin B12 levels were within the normal range in both dialyzed and renal transplant patients.

Successful outcome of a complicated pregnancy in a renal transplant recipient taking cyclosporine A.

The successful outcome of a pregnancy complicated by reversible renal failure secondary to total ureteral obstruction caused by a pregnant uterus and treated temporarily with nephrostomy is reported. The cyclosporine A (CsA) and prednisone treated female recipient of a cadaveric renal allograft gave birth to a male child, which at 2080 grams was small for gestational age (35 weeks of pregnancy). The child presented neither signs of congenital anomalies or chromosome aberrations nor nephrotoxicity, hepatotoxicity or anemia. Simultaneous measurement of trough CsA blood levels (CsA RIA, Sandoz) displayed reduced values in the child's blood (mother 864 ng/ml-4 hours after oral CsA intake; son 312 ng/ml). Beside postrenal failure the patient's pregnancy was complicated by 7 rejection episodes treated with high doses of methylprednisone (total dose 5 g) with reversible damage of the transplant function, two episodes of a urinary tract infection and increasing anemia necessitating blood transfusions. The HIV negative patient had developed a Kaposi's sarcoma 6 weeks after grafting. The progression of infiltrating skin lesions during pregnancy was not seen.

Serum-erythropoietin concentration during acute cardiogenic pulmonary edema.

Reduced oxygen tension is regarded as the primary physiologic signal for the production of erythropoietin (EPO). There is little information available about early changes of EPO production in man due to severe hypoxia. The purpose of the present study was to examine the time course of EPO in serum of patients with acute cardiogenic pulmonary edema (ACPE). In 29 patients (seventy-five +/- six years, mean age +/- SEM) who were hospitalized within two hours after onset of symptoms of ACPE, serum EPO concentrations were monitored for up to seventy-two hours. At the moment of admission all patients showed significantly increased EPO concentrations of 121 +/- 64 mU/mL (mean +/- SEM) compared with a healthy population (15-35 mU/mL). Twenty-three patients who recovered within thirty minutes (group A) exhibited a quick return of their EPO serum levels to normal. The remaining 6 patients (group B) had a protracted clinical course and their EPO concentration showed a further increase up to the end of the observation period. The comparative monitoring of concentrations of alpha-1-proteinase inhibitor, antithrombin III, C-reactive protein, fibronectin, hapotoglobin, and transerrin in serum and plasma revealed no significant changes. Thus a major contribution of fluid shifts into or from the intravascular compartment to the observed changes in EPO concentration seems to be unlikely. The data suggest that the production and release of EPO in the kidneys due to altered oxygen delivery is a fast-responding mechanism.

[Serum gastrin following renal transplantation]. / Serumgastrin nach Nierentransplantation.

Basal and postprandial serum gastrin concentrations were determined in 26 renal transplant patients and compared with the values found in 5 normal subjects. All subjects received a solid test meal consisting of 25 g protein, 47 g fat and 58 g carbohydrates. All patients were in a non-uraemic state and received combined prednisolone-azathioprine treatment. 5 patients had a peptic ulcer. There was no significant difference in the mean serum gastrin concentrations of the two groups, either with respect to basal or postprandial values. On calculating mean gastrin concentrations of patients given high (over 20 mg daily) or low (under 20 mg daily) prednisolone dosage, again no difference was found in comparison with the normal subjects. Similarly, no difference was observed in the mean serum gastrin levels between ulcer patients and normal controls. We conclude from these results that, in contrast to the findings in chronic uraemic patients, gastrin metabolism is normal in renal transplant recipients and that the high indicence of gastrointestinal complications, especially peptic ulcer, cannot be due to a disturbed gastrin metabolism in these patients.

[Frequency of cardiovascular risk factors in renal transplant patients (author's transl)]. / Häufigkeit potentieller Risikofaktoren kardiovaskulärer Erkrankungen bei nierentransplantierten Patienten.

The incidence of cardiovascular risk factors was studied in 83 renal transplant recipients: 84.3% showed at least one cardiovascular risk factor, hyperuricaemia was found in 42.2%, hypertension in 39.7%, hypercholesterolaemia in 31.3%, hypertriglyceridaemia in 27.7%, diabetes mellitus in 19.3%, obesity in 14% and nicotine abuse in 13.2% of the patients. Patients aged from 30 to 39 and 40 to 49 showed a mean incidence of 2.7 and 2.9, respectively out of the 7 investigated cardiovascular risk factors. The results demonstrate that renal transplant patients are a high-risk group for the development of degenerative cardiovascular diseases.

[Mixed infection after renal transplantation (author's transl)]. / Mehrfachinfektionen nach Nierrentransplantation.

Severe mixed infection was observed in 9 out of 101 renal transplant recipients over a period of 6 years and was characterized by the simultaneous incidence of bacterial, fungal and viral infections. Severe septicaemia was clinically evident in all cases. The critical clinical situation called for a rapid assessment of the differential diagnosis and relevant bacterial, fungal and viral investigations. Antibacterial and antimycotic therapy must be instituted as soon as possible on account of the high mortality from mixed infection in renal transplant recipients. The reduction or discontinuation of immunosuppressive therapy during infection did not impair renal transplant function.

[Morbidity during regular dialysis treatment and after renal transplantation (author's transl)]. / Morbidität während chronischer Hämodialyse und nach Nierentransplantation.

Renal transplantation was associated with a lesser degree of morbidity than chronic dialysis treatment in a group of 48 patients with end-stage renal failure. Morbidity was defined as total days of in-patient hospitalization divided by total days of risk. The morbidity during chronic intermittent dialysis, with a mean observation time of 296.1 (20 to 2255) days, was 11.8%, whereas after renal transplantation, with a mean observation time of 1004.0 (131 to 2400) days, only 7.6% of all days at risk were spent in hospital. Morbidity rises to 38.1% during chronic dialysis if all dialysis days on an out-patient basis are considered as hospitalization days. Morbidity was lowest (3.8%) in patients sent home for the first time with a functioning graft. Cardiac complications and fluid lung were the most common causes for morbidity during haemodialysis treatment; morbidity after renal transplantation was mainly due to renal rejection and infections under non-specific immunosuppression. Social and occupational rehabilitation was better after renal transplantation than during haemodialysis treatment. It can be concluded from these data that with regard to the quality of life renal transplantation is the preferable alternative in the management of end-stage renal failure.

["Membrane attack complex" formation in hemodialysis treatment]. / Die "Membrane attack complex"-Bildung während der Hämodialysebehandlung.

The behaviour of plasma concentrations of the membrane attack complex (MAC) during haemodialysis was studied in 23 patients. An increase in the levels up to 250% of the initial value was noted when Hemophan or Cuprophan membranes were used. Patients dialyzed, with Polysulfon membranes showed only a slight increase in MAC levels. In the Hemophan and Cuprophan group a plateau developed lasting from 15 to 120 minutes after onset of the haemodialysis session. The MAC may serve as marker of biocompatibility. Furthermore, it seems to be involved in many untoward effects of haemodialysis treatment.

[Fungal infections -- always dangerous for immunosuppressed patients (author's transl)]. / Pilzinfektionen -- weiterhin gefährlich für den immunsuppressiv behandelten Patienten.

Four renal transplant recipients, treated with the immunosuppressive combination of azathioprine-prednisolone, developed organ or systemic mycoses caused by Candida albicans and, in one case, additionally by Trichophyton rubrum. Ketoconazole, a new wide-spectrum antimycotic drug, was successfully used in the treatment of the fungal infections in these patients. The oral route of administration, good tolerance and excellent results are good recommendations for this drug.

[Plasma glycolate concentrations under conditions of dialysis]. / Plasma-Glykolatkonzentration unter Dialysebedingungen.

Plasma glycollate and oxalate concentrations were measured in 20 patients undergoing chronic haemodialysis treatment. The mean plasma glycollate level was 173.7 +/- 52.9 mumol/l, which was not significantly different from the normal value (means = 145.8 +/- 37.8 mumol/l). The mean plasma oxalate concentration (means = 128.7 +/- 25.6 mumol/l) was about 8 times higher than the value found in normal volunteers (means = 16.8 +/- 6.0 mumol/l). During haemodialysis lasting for 6 hours the plasma oxalate concentration decreased by 53.5%. However, no decline in plasma glycollate levels was noted. Since glycollate was not found in ultrafiltrates obtained in vivo, it is concluded that glycollate is not eliminated during haemodialysis treatment.

[Cyclosporin therapy in minimal change nephritis]. / Cyclosporintherapie bei Minimal-change-Nephritis.

In 5 cases with minimal change nephritis Cyclosporine A has been added to the conventional steroid therapy, when relapse of nephrotic syndrome occurred while reducing the daily prednisolone dose. The intended cyclosporine trough level ranged from 250 ng/ml to 450 ng/ml whole blood, estimated by the RIA method. Proteinuria disappeared in 4 out of the 5 cases, in the other one urinary protein excretion was strikingly reduced. In the 4 cases with complete remission of proteinuria prednisolone was tapered. These patients have cyclosporine A as the sole immunosuppressive drug since 56 weeks and do not show proteinuria. Side effects of cyclosporine therapy have been slight deterioration of kidney function in 2 out of the 5 cases and the occurrence of hypertension in 4 patients.

[Comparative pharmacokinetics of the beta-1 receptor blookader celiprolol after a single oral administration in subjects with health kidneys and in patients with impaired renal function]. / Vergleichende Pharmakokinetik des Beta 1-Rezeptoren-Blockers Celiprolol nach oraler Einzelgabe an Nierengesunde und an Patienten mit eingeschränkter Nierenfunktion.

Pharmacokinetic parameters were determined after the oral administration of a single tablet containing 200 mg celiprolol HCl to 8 healthy volunteers with normal kidney function and 6 patients with stable impaired renal function of different degrees of severity. The plasma levels and the urinary excretion of celiprolol were followed up for 48 hours after administration with the help of specific chemo-analytical methods. The substance was equally well absorbed both by healthy volunteers and patients with renal disease. While the cumulative renal excretion (0 to 48 hours after administration) was reduced from 18.2% in healthy volunteers to 2.3% of the applied dose in kidney patients, the global elimination constant k fell from 0.104 h-1 in healthy volunteers to 0.072 h-1 in the patients with renal disease. It can be assumed that in patients with impaired renal function at least a part of the lacking renal elimination of celiprolol can be taken over by "extrarenal elimination". According to the method of Dettli a reduction in dosage of the beta 1-blocker, celiprolol is not necessary in patients with more or less impaired kidney function.

[Serum lactate dehydrogenase activity after renal transplantation (author's transl)]. / Serum-Laktatdehydrogenase-Aktivität nach Nierentransplantation.

Regular 4-weekly follow-up controls of serum lactate dehydrogenase activity in 23 renal transplant recipients revealed a constant rise in serum LDH activity during the early postoperative months. During the first post-transplant month serum LDH activity increased from 150.0 +/- 48.2 mE/ml to 195.5 +/- 84.8 mE/ml, serum enzyme activity being highest (329.1 +/- 143.2 mE/ml) 6 months after surgery. Since serum creatinine levels remained relatively constant, it seems unlikely that renal rejection played a major pathogenic role in the production of increased LDH activity. Since the pattern of lactate dehydrogenase isoenzymes was ithin normal limits, the pathogenesis of increased LDH serum activity following renal transplantation is not yet clear. Possible causes such as liver damage due to hepatitis B, macrocytosis induced by immunosuppressive therapy and myopathy to steroids are discussed.

[Behaviour of serum and urinary lysozyme after renal transplantation (author's transl)]. / Verhalten des Lysozyms in Serum und Harn nach Nierentrasplantation

The behaviour of serum and urinary lysozyme was investigated before and after renal transplantation in 20 patients. The mean postoperative observation time was 67.8 (10 to 212) days. In 11 patients with reversible olig-anuria due to prolonged preoperative ischaemia, lysozymuria lasted for a period of 17 days after surgery, whereas in 8 patients with immediate transplant function lysozymuria disappeared 7 days after transplantation. Serum lysozyme concentrations were markedly elevated before transplantation in all patients. In patients with transplant failure due to ischaemia, normalization of serum lysozyme levels was achieved 28 days after surgery; patients with immediate function showed normal serum lysozyme levels already 7 days after transplantation. Prolonged lysozymuria was also noticed in 2 cases with irreversible ischaemic transplant failure, in 1 case with recurrence of glomerulonephritis and in 1 further case with acute pyelonephritis in the transplant. In 7 cases with an acute renal rejection crisis, lysozymuria was evident 0.7 days before clinical diagnosis of rejection. Serum lysozyme levels showed a strong correlation with serum correlation with serum creatinine concentrations. Therefore, lysozymuria in renal transplant patients indicates tubular transplant damage of varied aetiology. Elevated serum lysozyme levels, on the other hand, seem to reflect a reduced glomerular filtration rate.

[Prolonged renal graft survival after repeated blood transfusions (author's transl)]. / Verlängerte Funktionsdauer von Nierentransplantaten nach Mehrfachtransfusionen.

In order to investigate the influence of pretransplant blood transfusions on renal graft survival, the results in 43 recipients with 10 or more transfusion (group A) were compared with those in 48 recipients with less than 10 or no transfusions (group B). In both groups cadaveric kidneys with mainly 3 or more mismatched histocompatibility antigens were transplanted. The incidence of preformed cytotoxic antibodies was similar in both groups (25.6% and 22.9%, respectively). The cumulative renal graft survival rate was significantly higher in the poly-transfused group: 85.6% +/- 6.1% and 73.4 +/- 7.9% after 1 and 2 years, respectively, in group A in comparison with 73.9 +/- 6.6% and 63.3 +/- 8.1% after 1 and 2 years respectively, in group B (Wilcoxon rank sum test: p less than 0.05). Severe renal rejection with a serum creatinine above 3 mg/100 ml was more frequently observed in group B than in group A. Enhancement due to blocking antibodies must be assumed as a possible explanation for the favourable effect of repeated pretransplant transfusions on graft survival rates.

[Experiences and clinical results following 99 kidney transplantations with kidneys from relatives]. / Erfahrungen und klinische Ergebnisse nach 99 Verwandtennierentransplantationen.

99 living related kidney transplantations were performed between January 1967 and December 1988. At the time of observation 4 of 94 organ donors had died; there was no correlation between unilateral nephrectomy and the patient's death. Intraoperative (2.9%) and postoperative (25%) complications did not result in severe physical consequences for the organ donors. Hypertension was found in 2 donors. There was no decrease in function of the remaining kidneys. The 3-year organ survival of the transplanted kidney was 60% with "conventional immunosuppression" and 93% with cyclosporin. No association was found between HLA DR-matching and graft survival. Rejection episodes occurred significantly more often in the HLA DR-mismatched grafts.