[Dental treatment of allogenic organ transplant patient. 1. General indications].
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Biomedical subjects
Publications and source records attributed to U Frei.
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Disseminated mycobacterial infections occurred in two female renal graft recipients late after transplantation. In the first patient, initially presenting with fever, diagnosis was made at autopsy. Temporary defervescence following antibiotic therapy with ofloxacin possibly contributed to the fatal diagnostic delay. In the second case, body temperature was normal throughout the protracted course of the patient's illness. Her presenting symptom was rapidly increasing ascites, attributed initially to chronic liver disease. These cases demonstrate that tuberculosis remains a serious complication after renal transplantation, in particular due to its sometimes atypical clinical manifestations. Response to antibacterial therapy has to be critically evaluated in order to avoid fatal diagnostic delay.
We analysed our population of renal transplant recipients treated with cyclosporin (CsA) and prednisolone with respect to clinically evident de novo malignancies. Eighteen of 598 patients (mean age 35.6 (1-73) years receiving their first renal graft between 1 May 1981 and 31 December 1986 developed a malignancy at a mean interval of 33.5 months. Types of malignancy were squamous carcinoma of the skin (1), carcinoma of the tonsils (1), urothelioma (5), renal-cell carcinoma (2), adenocarcinoma of colon and liver (3), metastic adenocarcinoma of the lung (1), teratocarcinoma of the testis (1), breast cancer (1), Hodgkin's lymphoma in the renal allograft (1), carcinoma of the uterus (1), and carcinoma of the prostate (1). Six cases were observed in the age group 40-49 years (3%), but only three in age group 20-29 years, and nine cases in patients older than 50 years. No malignancy emerged in children (age group less than 19 years) and in patients with pretransplant malignancies. Five patients with analgesic abuse (n = 21 of 598 patients) developed malignant urotheliomas. It is concluded that de novo malignancies constitute a heterogeneous group with no obvious risk attributable to CsA treatment. As previously reported there is a special risk of malignant urotheliomas in patients with analgesic nephropathy. The risk in children seems to be low. We did not observe the high incidence of lymphomas and skin cancer reported by other groups.
To examine the role of renal excretory function for erythropoietin (EPO) formation we have determined the kinetics of plasma immunoreactive EPO (irEPO) in patients with end-stage renal disease undergoing renal allotransplantation (RTX). In 13 patients with immediate excretory graft function (imGF) and stable haemoglobin (Hb) concentrations (median Hb 9.5 g dl-1 and median irEPO 18 mU ml-1 before RTX) irEPO increased significantly on day 4 after RTX to a median value of 29 mU ml-1 and 2 days later reached a plateau of 34.4 +/- 3.3 mU ml-1 (mean +/- SD of daily median values during days 6-20). In patients with imGF having acute blood loss and subsequently receiving transfusions, irEPO responded in an inverse fashion to changes in Hb concentrations. In 12 patients with delayed graft function (dGF) (median Hb 8.8 g dl-1 and median irEPO 15 mU ml-1 before RTX) irEPO levels during the period of excretory failure remained either unchanged or displayed marked variations with peak values greatly exceeding those of patients with imGF. These variations were not related to changes in Hb concentrations and irEPO levels did not change following alterations in Hb concentrations. Upon recovery of excretory function irEPO approached the values found in patients with imGF. The results suggest that an intact excretory renal function is not a prerequisite for the capability to produce EPO, but correlates with the oxygen-dependent regulation of EPO formation.
The case of a patient with acute occlusion of the right renal artery due to an embolus is described. Using transoesophageal echocardiography, the left atrial appendage could be identified as the source of embolism. Twenty hours after the onset of symptoms, the embolus could be successfully dissolved with an intra-arterial low-dose infusion of recombinant tissue-type plasminogen activator (10 mg loading dose, 20 mg continuous infusion within 12 h).
The in vivo functional characteristics of continuous arteriovenous hemofiltration (CAVH) were studied in 21 intensive-care patients with acute renal failure. FH-66 hemofilters were applied. The relationships between prefilter blood pressure (BP), blood flow (QB) and filtration rate (QF) were evaluated by stepwise clamping of the arterial access and simultaneous measurements of these parameters. The correlations between BP and QB, and between QB and QF, were linear (p less than 0.001). The total pressure drop across the extracorporeal circuit was 90 +/- 12 mmHg with Scribner shunt and 70 +/- 13 mmHg with femoral catheters as vascular access. The relative pressure drops across arterial access, hemofilter and venous access for Scribner shunt and for femoral catheter were 30%, 43% and 27% and 12%, 74% and 14%, respectively. At a given BP, QB was lower and transmembrane filtration pressure (TMP) higher in CAVH with Scribner shunt. QB was 102 +/- 38 ml/min; QF was 20 +/- 7 ml/min. The effects of hemofilter geometry and membrane material on functional parameters of CAVH were evaluated by applying four hemofilters (Amicon D-20 HP, D-30 HP, Gambro FH-66, Fresenius AV-400) consecutively in the same patient. The filters were different with respect to hollow fiber length, its internal diameter, number of fibers and membrane material. BP, hematocrit (Hct) and plasma protein remained constant during measurements. QB increased with decreasing filter resistance. QF did not increase with increasing QB. QF was also not closely related to membrane surface area. The hydraulic permeability (Lp) had a major impact on QF.(ABSTRACT TRUNCATED AT 250 WORDS)
The analysis of the hemodynamic parameters involved in the regulation of blood pressure during correction of anemia shows - although peripheral resistance and cardiac output behave qualitatively as in the nonuremic patient - that the extent of change may be inadequate resulting in an increased blood pressure. The underlying mechanisms are not yet fully understood but to a greater part may be related to preexisting pathology due to a history of long-lasting hypertension. To avoid cardiovascular complications under rhEPO therapy the following should be considered: patients with a history of hypertension, even if they are normotensive in the anemic state, are at a higher risk for developing hypertension under rhEPO. Hypertensive complications may be rare events when anemia is corrected slowly. Further studies will demonstrate whether in addition to the benefit of a very low maintenance dose of rhEPO subcutaneous administration will also contribute to the reduction of the incidence of hypertension.
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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)
A 56-year-old patient with deep vein thrombosis shown by phlebography developed a massive pulmonary embolism during perfusion ventilation lung scanning with complete occlusion of the main pulmonary artery branch. 40 minutes after beginning of symptoms the patient suffered from persistent heart failure. Under external heart massage and controlled ventilation a cardio-pulmonary bypass was established after sterniotomy. After manual manipulations to express peripheral emboli pulmonary embolectomy and cava clipping was performed. The patient recovered without neurological damage.
The aim of this study was to determine the effect of two years of treatment with cyclosporine A on blood pressure and the rates of secretion into the circulation of the vasoconstrictor thromboxane A2 and the vasodilator prostacyclin. Seven patient suffering from multiple sclerosis took part. Their blood pressures and urinary concentrations of 2,3-dinor-thromboxane A2 (a major urinary metabolite of thromboxane A2) and of 2,3-dinor-6-keto-prostaglandin F1 alpha (the major urinary metabolite of prostacyclin) were determined at the end of two years of treatment with cyclosporine A, and once again three months after cessation of this treatment. No other drugs were given during or after cyclosporine A. Mean arterial blood pressure was 113 +/- 5 mmHg (mean +/- SEM) during the cyclosporine A treatment, but fell to 94 +/- 4 mmHg after the three-month's wash-out period. Urinary excretion of the thromboxane metabolite decreased slightly from 674 +/- 150 pg.mg-1 creatinine during cyclosporine A therapy to 503 +/- 90 pg.mg-1-creatinine after the end of therapy. At the same time the prostacyclin metabolite increased significantly from 82 +/- 17 pg.mg-1 creatinine to 113 +/- 23 pg.mg-1 creatinine (P less than 0.05). The ratio of 2,3-dinor-thromboxane B2 to 2,3-dinor-6-keto-prostaglandin F1 alpha (taken as a measure of vasoconstrictor prostanoid activity) fell significantly from 8.4 +/- 0.8 4.7 +/- 0.6 (P less than 0.005). The shift in prostanoid production observed during cyclosporine A treatment could be one causal factor for the hypertensive and thromboembolic events associated with the use of this drug.
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From 1984 to 1987, offspring from six renal transplant-patients were delivered in the Department of Obstetrics and Gynaecology of the Medical School of Hannover. The patients received cyclosporine and cortisone as an immunosuppressive therapy during the pregnancies. All pregnancies ended with live births; in two cases, a caesarean section was performed. Serious congenital malformations of the newborns were not observed, only two newborns being small. In the blood of the newborns, the cyclosporine concentrations were between 85 and 65% of the maternal blood levels. In two patients, the kidney functions deteriorated significantly during and after pregnancy. An increase in blood pressure or a hypertonic crisis, however, did not occur.
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The available data from experimental and clinical studies suggest that in the development of hypertension following correction of renal anemia under rhEPO three mechanisms are operative: (1) an increase in whole blood viscosity; (2) possible also a reduction of hypoxic vasodilatation, and (3) at least in some patients an inadequate reduction of cardiac output. To avoid cardiovascular complications under rhEPO therapy, the following should be considered: Patients that were hypertensive before the start of renal replacement therapy, even if they were normotensive in the anemic state - because of morphological alterations of their peripheral vascular bed-may run a higher risk for developing hypertension under rhEPO. As patients with undetected volume contraction may be more endangered by cardiovascular complications, the hematocrit should be monitored before and after dialysis, especially in patients with high weight gain and in children. Patients who are hypertensive under rhEPO therapy should be treated by antihypertensive drugs as appropriate. Drugs of the first choice are beta-blockers and vasodilating agents. Volume removal should not be the sole measure for blood pressure control and should be applied carefully. To avoid hypertensive and rheological complications, the target hematocrit should not exceed 30 vol%.
Erythropoietin (EPO) formation in kidneys of 18 patients with autosomal dominant polycystic kidney disease (ADPKD) was investigated. In 12 patients on hemodialysis and in 6 patients with preterminal renal failure serum, EPO was 29 +/- 7 and 16 +/- 1.5 mU/ml and hemoglobin concentrations were 11.0 +/- 0.6 and 12.7 +/- 1.2 g/dl, respectively. Cyst fluid from a total of 357 renal cysts was obtained by either in vivo aspiration or immediately after nephrectomy. The cysts contained variable concentrations of bioactive EPO from undectable values up to 3.2 U/ml. A pronounced enrichment of EPO was observed in cysts with sodium concentrations greater than 100 mmol/liter, suggesting an association with proximal tubular malformations. The EPO concentrations in the cysts were neither correlated with the protein concentration nor with the oxygen pressure of the cyst fluid. Using a cDNA probe for human EPO, mRNA for EPO was localized in stroma cells of the cyst walls by an in situ hybridization technique. Our findings suggest that single interstitial cells juxtaposed to proximal tubular cysts may produce EPO independent of the oxygen pressure inside the cysts, which ameliorates the anemia during end-stage polycystic kidney disease.
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Kidney and liver transplantations are well established surgical procedures. During the past years survival rates have improved 3% of kidney transplantations have 1-year mortality. Subjective quality of life and professional rehabilitation are associated with the graft function parameters of successful therapy. Seventy-six percent of liver-transplanted patients consider their quality of life improved after the operation. 52% are able to return to work. Future efforts must focus on improving immunosuppression for specific tolerance and sensitizing the public to the problems of obtaining organs for transplantation.