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Biomedical subjects

U Frei

Publications and source records attributed to U Frei.

17 recordsLinked to original sources

Influence of antihypertensive therapy on renal function.

Antihypertensive therapy influences kidney function by different mechanisms depending on the mode of action of the drug used. The GFR is improved by calcium entry blockers and ACE inhibitors, unaffected by vasodilators, alpha-blockers and centrally acting sympatholytics and impaired by beta-blockers. The same is true for renal blood flow and is due to changes of renal vascular resistance. Renal sodium excretion is impaired mostly by vasodilators, by alpha-blockers, sympatholytics and beta-blockers; in contrast, calcium entry blockers and ACE inhibitors acutely induce natriuresis. The RAAS is stimulated by vasodilators, unaffected by alpha-blockers and sympatholytics and suppressed by beta-blockers. Plasma catecholamines are stimulated by vasodilators and suppressed by centrally acting sympatholytics and unaffected by the others. Induction of acute renal functional impairment is reported for ACE inhibitors under conditions of compromised renal perfusion pressure such as in renal artery stenosis. These data from the literature reviewed are supported by our own experimental data on sodium balance under different drugs and micropuncture data in experimental renal artery stenosis. To achieve effective antihypertensive treatment with a low profile of side effects, careful monitoring of renal function seems to be mandatory.

Animals

Present status of kidney transplantation.

Kidney transplantation today is the method of choice to treat end-stage renal disease (ESRD) in more than 50% of the ESRD-population. Due to major improvements in surgical handling, immunosuppressive therapy, and infection control, the one-year survival for patients and first grafts has reached nearly 90% in the recent years. In contrast no comparable achievements have been made in long-term graft survival. A constant number of grafts is lost yearly after the first postoperative year. In addition an increasing number of well functioning grafts is lost due to the death of the recipients caused mainly by cardiovascular and malignant disorders. The extension of kidney transplantation to all suitable recipients is nearly exclusively hampered by the organ shortage, which is further enhanced by failing grafts. This urges us to further improve the prognosis for patient and graft. This must include organ sharing on the basis of improved HLA-typing to achieve highly compatible grafts. The tools for differential diagnosis of acute and chronic graft dysfunction have to be improved. New immunosuppressive agents with higher immunosuppressive power and specificity but fewer nephrotoxic, metabolic and hemodynamic side effects are required at least for chronic rejection. The risk of infectious and malignant complications must be limited.

Cadaver

Kidney transplantation in Alport's syndrome: long-term outcome and allograft anti-GBM nephritis.

Anti-glomerular basement membrane (anti-GBM) nephritis occurring in kidneys transplanted in patients with Alport's syndrome (AS) has been reported repeatedly. Therefore, we studied graft survival and course of renal function in all 30 AS patients grafted at Hannover Medical School and compared them with non-diabetic, age and sex matched patients, transplanted on the date closest to the transplantation of the AS patient. Serum creatinine, proteinuria, urinary sediment and anti-GBM antibodies were examined in all AS patients with functioning grafts. Cases of patient or graft loss in the AS group were analyzed retrospectively. One- and five-year patient survival was 100 and 91% in AS and 89 and 78% in controls (p > 0.05, respectively). One- and five-year first graft survival was 79 and 66% in both groups. Graft histology was available in 34 biopsies obtained from 21 kidneys in 15 AS patients. Anti-GBM nephritis was not detected in any of the biopsies. No graft was lost due to anti-GBM nephritis. Anti-GBM antibodies were detectable temporarily only in one AS patient. He also had linear IgG staining in his graft GBM, but no other signs of anti-GBM nephritis. We conclude that patient survival and graft survival in AS patients following kidney transplantation is not different from non-AS patients. Allograft anti-GBM nephritis is a rare complication in patients with Alport's syndrome.

Adult

Glomerular hemodynamics of the clipped kidney: effects of captopril and diltiazem.

Glomerular hemodynamics of the clipped kidney in two kidney-one clip Goldblatt-hypertensive rats were studied by micropuncture techniques after administration of either captopril (20 mg/kg of b.wt./day p.o.) or diltiazem (3 mg/kg of b.wt./hr i.v.). Both drugs decreased mean arterial and poststenotic renal arterial pressure to comparable levels. Total kidney glomerular filtration rate was not significantly different in the three groups (0.78 +/- 0.09 in hypertensive controls, 0.62 +/- 0.11 after captopril and 0.74 +/- 0.07 ml/min/g of kidney weight after diltiazem). Glomerular capillary pressure fell significantly in both treated groups but was lower in captopril-treated animals (60 +/- 2 in hypertensive controls, 45 +/- 2 after captopril and 53 +/- 1 mm Hg after diltiazem, both P < .05 vs. hypertensive controls). Afferent arteriolar resistance was lowered in both treatment groups to the same extent, whereas only captopril decreased efferent arteriolar resistance. Single nephron filtration rate of cortical nephrons was not altered significantly by captopril due to a 96% increase in the ultrafiltration coefficient and a 58% rise in glomerular plasma flow, whereas diltiazem increased ultrafiltration coefficient by 62% but did not affect glomerular plasma flow. These studies indicate that, despite of decreased effective filtration pressure, glomerular filtration rate is well preserved after converting enzyme inhibition. Captopril and diltiazem have different effects on glomerular hemodynamics within the stenosed kidney.

Angiotensin II

[Pregnancy following organ transplantation].

Pregnancies following organ transplantation are high-risk pregnancies for mother and fetus. There are many reports concerning pregnancies following renal transplantation whereas only few reports are published about pregnancies in recipients of liver, heart and bone marrow transplants. During the pregnancy after kidney transplantation pregnancy-induced hypertension can develop or the renal function can decrease. Risks for the fetus are prematurity, growth retardation and prenatal infections. A higher incidence of complications for mother and fetus is observed in patients with renal insufficiency or severe hypertension prior to conception. The risks can be reduced by an intradisciplinary cooperation of gynecologist, transplant specialist and paediatrician. The paediatrician. The experiences with pregnancies in women after organ transplantations in the Medical School of Hannover are analyzed and compared with the reports in the literature. The management of these patients is described on current state of knowledge.

Female

Calcium channel blockers for kidney protection.

Acute postischemic renal failure (ARF) is a major complication in surgery and in particular in renal transplantation. Calcium channel blockers (CCBs) are able to prevent or ameliorate ARF in different experimental models when given before ischemic injury. Because ARF, which is observed in 20-60% of graft recipients, carries the risk of undetected rejections and nephrotoxic injury and is also expensive, we tested the hypothesis, suggested by animal experiments, that there is also a beneficial effect of CCBs when given after ischemic injury. A total of 134 recipients of first or second cadaver grafts were randomly assigned to a diltiazem pretreatment (DZ) or control (C) group. Kidney grafts were pretreated immediately prior to transplantation by reperfusion with 500 ml Euro-Collins (preservation fluid), with or without DZ. The DZ patients also received a 74-h infusion of DZ (0.12 mg/kg/h), starting 2 h prior to surgery. DZ was continued (90 mg b.i.d. p.o.) until day 30. Immunosuppression consisted of low-dose steroids and cyclosporine A (CSA) (10 mg/kg p.o.). CSA was instituted 6 h after surgery and later adjusted to achieve whole-blood trough levels of 300-600 ng/ml [by polyclonal radioimmunoassay (RIA)]. A total of 129 patients were available for efficacy analysis. There were no significant differences concerning donor demographics, human lymphocyte antigen (HLA) match, or ischemic times. ARF was defined as a need for dialysis in the first week. Our data show a significant reduction in ARF in grafts pretreated with DZ.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury

Haemolysis due to formaldehyde-induced anti-N-like antibodies in haemodialysis patients.

During reuse of formaldehyde sterilized Kiil-dialysers, red cell survival, measured by means of 51Cr t/2, was significantly reduced (p less than 0.001) in 16 patients with anti-N-like positive sera, when compared with 19 antibody negative control patients (mean +/- SD: 16.5 +/- 2.7 versus 22.4 +/- 3.1 days.) In antibody negative patients (n = 10) replacement of formaldehyde sterilized dialysers by ethylene-oxide sterilized disposable dialysers resulted in a significant increase (p less than 0.002) of 51Cr t/2 (Mean +/- SD, days: Kiildialyser 16.3 +/- 1.9; disposable dialyser 20.3 +/- 3.5). This improvement took place, although antibody titres persisted during the 51Cr-measurements and declined thereafter only slowly. In antibody negative patients (n = 6) red cell survival did not increase, when formaldehyde as a sterilant was avoided. In antibody positive patients mean haematocrit rose significantly (p less than 0.05), whereas in none of the antibody negative patients a definite change of haematocrit occurred. The data demonstrate, that formaldehyde sterilisation of dialysers may cause antibody-mediated haemolysis contributing to the extent of renal anaemia. This immunohaemolysis may be corrected, in spite of continuing antibody persistance, when formaldehyde exposure is totally avoided, or possibly when minimized.

Antibody Formation

[Recurrent hyperparathyroidism following subtotal parathyroidectomy].

Recurrent hyperparathyreoidism occurred in 3 of 9 patients in terminal renal failure from 9 months to 2 years after an initially successful subtotal parathyroidectomy. In all cases we find temporary remission of clinical signs of hyperparathyreoidism after surgery. Our clinical experience provided by followup in these patients showed an insufficient biochemical and clinical control. We find recurrence in 3 cases and repeat neck exploration was indicated for 2 patients.

Humans

[Morphological aspects of parathyroid gland transplantation. Contribution on the clinical relevance of induced, invasive tissue growth].

The results of morphologic studies performed in 18 patients who had total parathyroidectomy and autotransplantation of parathyroid tissue into the forearm muscle are presented. All patients had long-standing renal disease with azotemia, hyperphosphatemia and high levels of parathyroid hormone. The histologic findings after total parathyroidectomy, before gland transplantation, are important for selection of parathyroid tissue for surgery. Diffuse hyperplasia with the development of multiple nodules of the parathyroids can possibly be adverse for the transplant. In one case, nine month after autotransplantation we found a tumor in the forearm, measuring 2.0 X 3.0 X 2.2 cm in diameter. Morphologic findings in this case before implantation showed diffuse hyperplasia with adenomatous nodules but no signs of carcinoma. The grafted parathyroid tissue after excision was seen with blood vessel invasion in the normal skeletal muscle. In the case of primary renal disease with secondary parathyroid hyperplasia, the light microscopic examination revealed an autonomous tumorlike adenomatous formation in the autografted parathyroid tissue, with graft-dependent hypercalcemia. The invasive growth with some signs of neoplasia following autotransplantation raises the question of the development of certain neoplasia.

Adult

Total parathyroidectomy with autograft of parathyroid tissue in treatment of secondary hyperparathyroidism.

In 16 patients with severe symptomatic hyperparathyroidism reduction of hyperplastic parathyroid mass was performed by total parathyroidectomy with autotransplantation of parathyroid tissue. In all patients except one serum parathormone (PTH) levels returned to normal and postoperative difficulties in calcium homeostasis were rarely observed. Fifteen patients had normal PTH levels after surgery. Graft function was proven in 10 cases, but in 5 cases graft function could not be definitely established with the methods applied. One graft failure was observed. Total parathyroidectomy with autotransplanation of parathyroid tissue is recommended as the treatment of choice when surgical correction of secondary hyperparathyroidism is necessary.

Adult

Factors predisposing to priapism in haemodialysis patients.

Clinical data and therapy of all male home dialysis patients of two centres were compared in order to establish predisposing factors to priapism. One centre (Frankfurt) had nine priapisms in 96 patients, whereas the other centre (Montpellier) had none in 59 patients. The only difference found were higher haematocrits in Frankfurt than in Montpellier. The highest haematocrits were found in the priapism patients. Further evaluation of the Frankfurt data showed that androgen therapy, high haematocrits and hypovolemia increase the risk of dialysis priapism. It is recommended to withdraw androgen therapy when the haematocrit is consistantly above 25%.

Adult