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Biomedical subjects

K Derfler

Publications and source records attributed to K Derfler.

At least 19 recordsLinked to original sources

Long-term follow-up of renal transplantation in type 1 and type 2 diabetic patients.

This study evaluated the long-term outcome of renal transplantation in type 1 (n = 25) and type 2 (n = 18) diabetic patients. Overall postoperative survival at 1 year was 69% in type 1 diabetes and 75% in type 2; at 5 years it was 62% in type 1 diabetes and 58% in type 2. Death was due mainly to cardiovascular disease (60%) and septic gangrene (20%). Outcome was examined in terms of graft function, which was poor in the majority (86%) of patients who died. Patients with fatal outcome suffered major vascular complications prior to renal transplantation and frequently had impaired graft function. Metabolic control was better in patients with good graft function (HbA1c < 6.2%) than in those with poor or no function of kidney transplant (HbA1c > 9.8%). In the absence of severe vascular complications renal transplantation may be the treatment of choice for both type 1 and type 2 diabetic patients with end-stage renal disease. Otherwise, renal transplantation is not able to improve the prognosis of patients with a history of severe vascular complications prior to renal replacement therapy.

Adult

Renal replacement therapy in type 2 diabetic patients: 10 years' experience.

The objective of this study was to determine the impact of renal transplantation and hemodialysis treatment on outcome of elderly diabetic patients with end-stage renal disease (ESRD) among other factors related to survival. Results of treatment of ESRD in 78 patients with non-insulin-dependent diabetes mellitus (type 2) showed a survival rate of 58% at 1 year and 14% at 5 years, independent of treatment modality. Patients who received a renal allograft had a higher survival rate as compared with patients on hemodialysis treatment (5-year survival, 59% v 2%; P < 0.005). Diabetic patients with a history of myocardial infarction, stroke, or peripheral gangrene before onset of renal replacement therapy had a worse prognosis in comparison to patients without vascular complications (5-year survival, 2% v 21%; P < 0.05). Analysis of patients who survived less than 6 months and more than 24 months was performed. Long-term survivors were slightly younger, had diabetes for a shorter period, and showed a better metabolic control of diabetes mellitus. Sixteen long-term survivors received a renal allograft. In contrast, only three short-term survivors were transplanted. Furthermore, short-term survivors also had a greater than 70% incidence of severe vascular complications before renal replacement therapy. A history of myocardial infarction, stroke, or peripheral gangrene is an independent predictor of decreased survival, irrespective of whether the patients were transplanted or maintained on chronic hemodialysis treatment. In contrast, renal transplantation improved survival of elderly diabetic patients without vascular complications and should be the treatment of choice in this specific group of patients.

Aged

T-cell selection and T-cell receptor variable beta-chain usage in chronic hemodialysis patients.

Thymic and extrathymic selection processes are responsible for the shape of the T-cell repertoire. T-cell receptor (TCR) variable (V) chain usage, holding a place in tolerance, autoimmunity and response to external agents, was analyzed in 41 patients maintained on chronic hemodialysis treatment. Leukocyte (mean: 6444 +/- 2277 cells/microliters), lymphocyte (mean: 1457 +/- 707 cells/microliters) and T-cell (mean: 67 +/- 16%) counts were within expected limits, but hemodialysis patients showed an impressive increase of TCR V beta 6.7 positive peripheral blood lymphocytes (PBL) and a massive deletion of TCR V beta 8 positive PBL. V beta 6.7 positive PBL were detectable in all hemodialysis patients (n = 41, mean: 2.47 +/- 1.61% PBL) in contrast to a healthy population, where only 45% of subjects expressed V beta 6.7 on PBL (n = 9, mean: 3.50 +/- 1.83% PBL). Only 27% of our hemodialysis patients expressed V beta 8 on PBL (n = 11, mean: 1.00 +/- 1.94% PBL) in contrast to healthy subjects, who presented V beta 8 positive PBL (n = 20, mean: 2.89 +/- 1.23% PBL) in every case. Neither primary kidney disease, nor response to vaccination for hepatitis-B, nor dialyzer membranes used, were associated with these alterations of the TCR V beta-pool. It is likely, that the well-known impairment of the cytokine network in chronic renal failure, uremic toxins or response to infectious agents, may contribute to these different and possibly independent T-cell selection mechanisms in uremia.

Cell Separation

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.

Acetaminophen

Decreased postheparin lipolytic activity in renal transplant recipients with cyclosporin A.

The patterns of hyperlipidemia in renal transplant recipients (RTRs) are more variable than in the uremic state, showing increases in both very low-density lipoprotein (VLDL) and low density lipoprotein (LDL). This has been attributed, at least in part, to immunosuppressive therapy, especially to treatment with corticosteroids. Postheparin lipolytic activity (PHLA) was determined in 28 RTRs. Sixteen patients presenting with hyperlipidemia comprised group A, who were aged 49.8 +/- 13.5 years, and had a cholesterol of 8.24 +/- 1.86 mmol/liter, triglycerides of 6.02 +/- 3.33 mmol/liter. Twelve patients presenting cholesterol and triglyceride values within the normal range were in group B, and were aged 48.6 +/- 13.3 years. All RTRs received cyclosporin A (CsA) twice daily orally, which were divided in two equal doses and adjusted to provide CsA blood trough levels (RIA) in a range of 250 to 350 ng/ml. Twenty-one RTRs were additionally treated by alternate-day corticosteroids, whereas seven patients had CsA on their sole immunosuppressive agent. PHLA (mumol free fatty acids/ml/hr, given 10 and 20 min after 100 U/heparin kg body wt intravenously) was commonly reduced in RTRs (group A at 10/20 min: 5.6 +/- 1.1/5.26 +/- 1.2; group B: 8.26 +/- 2.91/8.38 +/- 3.44) as compared to the values obtained in healthy controls (15.3 +/- 2.9/17.2 +/- 5.0). This was mainly due to a reduction of the activity of the hepatic triglyceride lipase, and to a minor extent to a reduced activity of peripheral lipoprotein lipase. There was no statistically significant difference of PHLA in RTRs with or without corticosteroid treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex Hormones

Anti-interleukin-1 alpha autoantibodies in hemodialysis patients.

IL-1 activity is increased in hemodialysis patients and interest has recently been focused on IL-1 antagonism in various clinical settings. We studied the presence of anti-IL-1 alpha autoantibodies in sera from 49 hemodialysis patients, 159 kidney graft recipients and 89 chronic renal failure patients without renal replacement therapy. Within the three month study period 32.6% of the hemodialysis patients were found to present with anti-IL-1 alpha autoantibodies, in contrast to 5.6% of kidney graft recipients, 8.9% of chronic renal failure patients, and only 1.4% of healthy subjects. The presence of these autoantibodies was neither associated with primary kidney disease nor with the type of dialysis membrane we used. In addition, in antibody positive patients a pronounced increase of IL-1 alpha serum levels within a dialysis session from 14.8 +/- 4.7 pg/ml to 26.4 +/- 11.2 pg/ml (P less than 0.0005) was observed, contrasting to the more even increase from 14.1 +/- 3.1 pg/ml to 19.3 +/- 12.7 pg/ml (P less than 0.05) in the antibody negative group. Neither clinical symptoms due to adverse effects of IL-1 alpha nor some influence on erythropoiesis mediated by IL-1 alpha could be envisaged. Thus, we believe, that anti-IL-1 alpha autoantibodies, present in high frequency in hemodialysis patients, have a neutralizing effect on IL-1 alpha in these patients.

Aged

Impaired conversion of cortisol to cortisone in chronic renal insufficiency--a cause of hypertension or an epiphenomenon?

To study the possible impairment of 11 beta-hydroxysteroid-dehydrogenase in patients with chronic renal insufficiency, urinary excretion rates of the four main glucocorticoid-metabolites, tetrahydrocortisol, tetrahydrocortisone, allotetrahydrocortisol and allotetrahydrocortisone were determined by capillary gas chromatography in 22 patients with chronic renal insufficiency with (N = 15) and without (N = 7) hypertension, but without hemodialysis treatment. Whereas the sum of all 41 steroid metabolites determined by capillary gas chromatography was reduced (p less than 0.001) in patients with chronic renal insufficiency as compared with 22 healthy individuals, the relative contribution of the four glucocorticoid metabolites to total steroid excretion was similar in patients with renal insufficiency (22 +/- 12%) and in healthy subjects (20 +/- 5%). However, the excreted amount of tetrahydrocortisol exceeded that of tetrahydrocortisone in all but 3 (normotensive) patients with chronic renal insufficiency, but only in one healthy subject resulting, in patients with chronic renal insufficiency, in a ratio of tetrahydrocortisone vs tetrahydrocortisone of 0.7 +/- 0.4 (hypertensive patients 0.5 +/- 0.2; normotensive patients 1.1 +/- 0.4; controls 1.9 +/- 0.9, p less than 0.001 vs patients with chronic renal insufficiency). This ratio of tetrahydrocortisone/tetrahydrocortisol showed a correlation with serum concentrations of creatinine (p less than 0.001). These results provide indirect proof of an impaired conversion of cortisol to cortisone in moderate renal insufficiency and may suggest a relationship with the hypertension frequently seen in this group of patients.

Adult

Duplex Doppler sonography in renal parenchymal disease. Histopathologic correlation.

To evaluate the histopathologic changes influencing Doppler measurements of the resistive index (RI) in renal arteries in renal parenchymal diseases, 68 kidneys in 34 consecutive patients with various forms of renal parenchymal diseases were studied by duplex Doppler ultrasound (duplex US) immediately before percutaneous renal biopsy. The RI, renal length, and renal cortical echogenicity were correlated with the amount of glomerular, interstitial, and vascular changes graded on a scale from 0 to 100. The renal vascular resistance and therefore the RI are significantly correlated with the prevalence of arteriolosclerosis, glomerular sclerosis, arteriosclerosis, edema, and focal interstitial fibrosis. There was no significant difference of the RI in five groups of different renal parenchymal diseases. Of 34 patients, 24 presented with an RI less than 0.7, which was thought to be within the normal range so far. Additionally, the RI increases as the patient's age increases, due to higher incidence of arteriosclerosis. Of our patients, 44% presented with normal cortical echogenicity. Quantitative duplex US using the RI does not reliably distinguish different types of renal medical disorders.

Adult

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).

Adult

[Beta-N-acetylglucosaminidase (beta-NAG) as a parameter in the diagnosis and evaluation of primary glomerular and tubulointerstitial kidney diseases].

beta-N-acetylglucosaminidase (beta-NAG) and beta 2-microglobulin were assessed in two cohorts of patients with glomerular or tubulointerstitial diseases respectively. While beta-NAG activities did not differ statistically significantly between both groups, beta 2-microglobulin excretion was statistically highly significantly increased in the setting of tubulointerstitial diseases. On the whole mean beta-NAG activity at 37 degrees C and beta 2-microglobulin urinary excretion were elevated in both groups, when compared to normal controls. Increased beta-NAG activities above 10 U/g creatinine were associated with a marked increase of creatinine serum levels within 6 months in both, patients with glomerular and tubulointerstitial basic renal diseases. beta-NAG and beta 2-microglobulin are useful tools in diagnosis and assessment of renal diseases elucidating different aspects.

Acetylglucosaminidase

["Membrane attack complex" formation in hemodialysis treatment].

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.

Complement Activation

[Experiences and clinical results following 99 kidney transplantations with kidneys from relatives].

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.

Adolescent

Generation of the membrane attack complex during haemodialysis: impact of classical and alternative pathway components.

1. The generation of the plasma SC5b-9 complex (the soluble form of the membrane attack complex) during haemodialysis was studied in 29 patients together with markers of the classical (C4d fragment) and alternative (Bb fragment) pathways and the common iC3b fragment. 2. In the patients dialysed with Hemophan and Cuprophan membranes, a rapid increase in the plasma levels of SC5b-9 complex, Bb fragment and iC3b fragment occurred within 15 min of the initiation of the haemodialysis procedure. The SC5b-9 complex and the Bb fragment concentrations remained at a plateau until 120 min thereafter. The iC3b fragment level showed a continual decline. 3. The C4d fragment concentrations remained unchanged, indicating that generation of the membrane attack complex is most likely due only to activation of the alternative pathway. 4. The generation of the membrane attack complex occurred throughout the full haemodialysis period. In patients treated with Polysulfon membranes no statistically significant variation in these components was noted. 5. The study shows that the membrane attack complex may be generated during the full period of the haemodialysis session and is a stable index of biocompatibility. 6. Moreover, it seems be involved directly in haemodialysis-associated phenomena.

Complement Activation