Biomedical subjects
Publications and source records attributed to G Keusch.
That the kidneys are vulnerable to damage by drugs is due to functional and morphological factors. Nephrotoxic reactions due to drugs may affect each segment of the nephron, the medullary interstitium and the renal vasculature, resulting in different nephrotoxic syndromes. The drug-induced nephropathies of special clinical importance are reviewed and the most common nephrotoxic agents mentioned.
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To overcome the shortage of kidneys (kdn's) available for transplantation we reactivated kdn procurement from non-heartbeating donors (NON-HBD). In this study, we reviewed our results with 34 kdn's from NON-HBD, transplanted between 1985 and 1991, and compared these with 34 control kdn's procured from heartbeating donors (HBD) matched for age, sex, primary graft or retransplant and transplant year. There was no difference in cold ischemia time, preservation solutions used, duration and type of preoperative dialysis, number of HLA mismatches and serum antibody levels between the two groups. The only significant findings were a lower diuresis in the last hour in the donors in the NON-HBD group, and a significantly higher serum creatinine level compared to the HBD group. The 1-year patient and graft survival rates were 89.4% and 84.9% for the HBD group, and 78% and 76.1% for the NON-HBD group respectively. There was need for dialysis support in the first posttransplant week in 10 out of 34 (29%) recipients in the HBD and 17 out of 34 (50%) recipients in the NON-HBD group. Primary non-function was observed in 1 of 34 (3%) recipients in the HBD group versus 3 of 34 (9%) in the NON-HBD group. None of the differences were statistically significant. There was also no difference in average serum creatinine levels at days 1, 3, and 7, at 1 month and at 1 year between the HBD and NON-HBD groups. In the NON-HBD group 6 of 34 kdn's (18%), 5 of which were retransplants, showed vascular rejection, 5 of them associated with haemolytic uremic syndrome (thrombotic microangiopathy); 2 of these 6 kdn's recovered, and 4 failed (2 with primary non-function). This important observation needs to be investigated further. The results is this study showed, however, that good short- and long-term results can be achieved with kdn's from NON-HBD. We concluded that organ procurement from NON-HBD is an adequate approach to an important cadaver donor source that in general is not effeciently used, but could significantly increase the number of kdn grafts in most transplant programs.
Sclerosing peritonitis is a serious complication of CAPD characterised by thickened peritoneal membranes which lead to decreased ultrafiltration and intestinal obstruction. The roentgenographic signs of SP were analysed in 11 patients who underwent plain x-ray of the abdomen, follow-through examinations of the small bowel, ultrasonography and computed tomography. Results were correlated with the histological degree of SP. Besides the non-specific findings of intestinal obstruction, patients with histologically marked SP had loculated fluid collections, thickening of the bowel wall and/or peritoneum, peritoneal calcifications and thickened peritoneal membranes. Due to the fact that postoperative complications often occur in patients with SP, detection of the radiological signs should lead to cautious surgical interventions and changeover to haemodialysis.
Heparin surface coated hemofilters and tubing sets were evaluated in comparison to identical but uncoated controls in 8 bovine experiments (74+/-6 kg). No heparin was given (neither systemically nor in the priming fluid). The hemofilters were primed with one liter of Ringer's lactate in both groups and the maximal filter performance (arterial line pressure 300 mmHg; transmembrane pressure (TMP) 500 mmHg) was measured over 6 hours or until filter occlusion. All coated and one control filter remained functional during the scheduled 6 hours. The mean filter patency was 360+/-0 minutes for coated versus 210+/-99 minutes for uncoated (p less than 0.01). Mean blood flow at 1 hour and 6 hours was 675+/-114 and 580+/-96 ml/min for coated versus 432+/-183 and 25+/-43 for uncoated (NS; p less than 0.01). Mean filter output during the 6th hour and total filter output over 6 hours was 4225+/-998 ml and 21779+/-4273 for coated versus 400+/-692 and 7717+/-9757 for uncoated (p less than 0.01; p<0.01). Mean lactatedehydrogenase (LDH) levels before and 30 minutes after hemofiltration were 1855+/-411 IU and 2007+/-635 for coated versus 2160+/-411 and 1945+/-500 for uncoated (NS; NS). The heparin coated hemofilters demonstrated improved thromboresistance resulting in superior filter performance. There was no evidence of increased blood trauma.
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Invasive methods of active removal, i.e., hemodialysis and hemoperfusion, are indicated for severely poisoned patients with substances causing tissue damage. Both methods will only be efficacious if the relative contribution of the extracorporal clearance to the overall elimination for a given substance is high and if the toxin has a relatively low apparent volume of distribution and a low tissue binding. Hemodialysis is recommended in severe life threatening intoxications with methanol, ethylene glycol, isopropyl alcohol, salicylates and lithium. Hemoperfusion is effective in removing theophylline and barbiturates. Patients with severe acute theophylline intoxication will benefit from hemoperfusion. Despite the very high clearance rates of barbiturates that can be obtained with hemoperfusion, the clinical usefulness of hemoperfusion remains to be proven.
In the same measure as the age of population is growing, the importance of the problems rising by the renal transplantation in elder persons is increasing. At the University Hospital of Zurich 1313 kidney transplantations were performed between 1964 and 1990, 44 of them to patients who at the moment of operation were older than 60 years of age. The actuarial patient survival after 3 months reached 81%, after 1 year 74% and after 5 years 42%. The actuarial allograft survival after 3 months was 75%, after 1 year 67%, after 5 years 40%. The mortality was 131 per 1000, the mortality ratio compared to a standard population 6 times higher. The main causes of death were infections (52%) and cardiovascular diseases (28%). These results explain our opinion, that renal transplantation in elder patients should be indicated retentively.
We studied retrospectively patients with hyperparathyroidism after successful renal allotransplantation. Since 1972, 1119 transplantations have been performed in our department, and 534 patients survive with functioning grafts. Hyperparathyroidism requiring parathyroidectomy developed in 32 (5.9%). The frequency of interventions increased markedly after introduction of cyclosporine A treatment in our unit. The time between transplantation and parathyroidectomy was 22.5 months (SD 16.5, range 1-82 months). The age of the patients was 49.0 years (SD 10.5, range 17-63 years); the group consisted of 16 female and 16 male patients. All patients but two (no measurement performed) repeatedly exhibited high serum parathormone and calcium levels and therefore underwent surgery. In comparison to a control group, matched for time of transplantation, age, sex, and cause of renal failure, the patients with hyperparathyroidism had longer dialysis treatment (54.2 months, range 9-132 vs 26.9 months, range 1-72) and exhibited lower phosphate concentrations in the early posttransplantation period. Before surgery, serum chemistry was different for hyperparathyroid and control subjects: serum calcium 2.80 +/- 0.23 mmol/l vs 2.48 +/- 0.13 mmol/l and alkaline phosphatase 157.4 +/- 92.0 U/l vs 85.2 +/- 51.5, respectively. We did not see any influence of oral phosphate binders, calcium supplementation, or vitamin D treatment on the development of parathyroid gland hyperactivity during dialysis treatment. Serum creatinine concentration did not change after parathyroidectomy. In four patients, long-term calcium supplementation after surgery was necessary.
Transient pure red cell aplasia (PRCA) in three consecutive patients receiving ATG for management of kidney graft rejection prompted a systematic study of the effects on erythropoiesis of the ATG preparation used at our institution. We found that 90% of patients treated with rabbit anti-T lymphoblast globulin developed reticulocytopenia (less than 17,000 reticulocytes/mm3), with complete disappearance of reticulocytes in 65% of patients and increased requirement for red cell transfusion. PRCA, with selective aplasia of erythroblasts was confirmed by bone marrow aspiration in 4 patients volunteering for aspiration, and by the kinetic of the disappearance of blood reticulocytes in relation to the beginning of ATG treatment. The nadir of thrombocytes and lymphocytes, blood cells directly destroyed by ATG in circulation, followed the start of ATG treatment within 1 to 4 days. In contrast the nadir of reticulocyte counts occurred later, between day 7 and 13 after ATG was begun, reflecting the fact that toxicity was directed against red cell precursors rather than mature circulating cells. In agreement with these clinical findings ALG was found to be cytotoxic in vitro for erythroid precursors. Analogously to autoimmune PRCA caused by autoantibodies to erythroblasts, this type of PRCA could be viewed as "heteroimmune disease."
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Spontaneous rupture of the kidney may occur as a complication of various congenital or acquired renal lesions. We describe three patients with non-traumatic rupture of the kidney, recently seen in our hospital. The rupture was related to polyarteritis nodosa in one case, and in the other two respectively to urothelial carcinoma and to acquired renal cystic disease in end-stage renal disease with continuous ambulatory peritoneal dialysis. In all patients the hemorrhagic complication led to a previously unsuspected diagnosis. After nephrectomy all patients did well. While spontaneous rupture of the kidney is very rare, it is important to consider this complication in the evaluation of a corresponding clinical picture. The possible causes of renal rupture are discussed.
The average platelet counts in our patients with functioning SPK were significantly higher during postoperative week 2 and the interval of weeks 5 through 9 compared with a matched group of KTA recipients. The thrombocyte values in the SPK group were consistently elevated above the normal range (except postoperative week 1) but less than a platelet level typically requiring therapeutic intervention (greater than 1 mil/mm3). However, because potential pathology both locally (graft pancreatitis, endothelial damage of preservation and operative trauma, diminished graft blood flow) as well as systemically (atherosclerosis, hypertension) is present in SPK patients, we consider them at high risk for thromboembolic complications and therefore support prophylaxis of post-SPK thrombocytosis with platelet inhibitors.
Alveolar hemorrhage (AH) is the result of diffuse bleeding into the acinar portion of the lung. Cardinal symptoms of AH include hemoptysis, dyspnea, alveolar filling opacities on chest roentgenogram, anemia and hypoxemia. However, AH is often misdiagnosed as pneumonia or pulmonary edema at the time of initial presentation. Isolated AH may occur but is more often seen in diffuse connective tissue diseases or in rapidly progressive glomerulonephritis. - At the Medical Clinic of the University Hospital of Zurich we have diagnosed AH in 18 patients (13 males, 5 females) over the last ten years (1978-1988). In 2 patients AH occurred as an isolated symptom: once due to occupational inhalation of fumes containing trimellitic anhydride, and once as so-called idiopathic pulmonary hemosiderosis. In 16 patients AH was associated with kidney disease, including the following disorders: vasculitis and collagen vascular disorders (9), rapidly progressive glomerulonephritis (4) and Goodpasture's syndrome (3). In 5 patients the presenting symptom was AH. 9 patients presented initially with renal symptoms and in 2 patients renal and pulmonary features occurred simultaneously. 7 patients died of the underlying disease or its complications. Both patients with isolated AH have survived. In the remaining 9 patients 1 required dialysis temporarily and 4 permanently. All patients except the one with AH due to inhalation of trimellitic anhydride were treated with immunosuppressive agents. - Since the pulmonary features are similar in each of the AH syndromes, diagnosis of the underlying disorder is heavily dependent upon pathologic evaluation of diseased extrapulmonary organs. Moreover, immunologic studies are essential. Failure to diagnose or treat AH syndromes in the early stages may have lethal consequences.
Thromboembolic episodes are one of the most serious complications in patients with nephrotic syndrome, with an overall incidence of 25%. The most frequent site of thrombosis is the renal vein, with a reported incidence varying from 2-42%. Arterial thromboses are much less common than venous thromboses, with an overall incidence of 3%. Clinical course of renal vein thrombosis may be acute or chronic. Renal venography is the method of choice in its diagnosis. Duplex scanning, computed tomography and magnetic resonance imaging may be as accurate as venography. Once the diagnosis of renal vein thrombosis is established, anticoagulation therapy should be started. Thrombectomy or thrombolytic therapy seem to have little to offer over oral anticoagulation. The increased incidence of thrombotic complications in nephrotic syndrome may be due to a hypercoagulable state distinguished by an increase in coagulation factors (V, VIII, X and fibrinogen); a decrease in the levels of coagulation inhibitors (antithrombin III, protein S); an increase in alpha 2-antiplasmin activity; and exaggerated platelet adhesiveness and aggregation. This pre-thrombotic state may be aggravated by additional rheological factors (immobilization, diuretic therapy etc.). Serum albumin has been found to be an appropriate parameter to assess the risk of thrombosis development in these patients. A serum albumin level below 20 g/l carries a high risk of thromboembolic complications. Prophylactic anticoagulation therapy is therefore indicated in patients with serum albumin below 20 g/l.
We describe a successful pregnancy in a 22-year-old patient with advanced renal failure, who gave birth to a living boy in the 35th week of pregnancy. At the time of spontaneous delivery the mother had a serum creatinine of 851 mumol/l. No dialysis treatment had been instituted during this successful pregnancy.
Hematological parameters and serum erythropoietin (EPO) levels were measured before and sequentially after grafting in 50 consecutive cadaver renal transplant recipients. EPO was estimated using a sensitive radioimmunoassay. Values for nonanemic controls were 15-25 mU/ml. Mean hematological values before transplantation were as follows: hemoglobin 9.7 +/- 2.4 g/dl; hematocrit 29 +/- 8%; corrected reticulocytes count 15 +/- 8% and EPO 29 +/- 23 (11-131) mU/ml. In the entire studied population, 35 patients had inadequate low EPO levels for their degree of anemia. In the whole population, there was a significant positive exponential correlation between EPO and hematocrit (r = 0.31; p less than 0.05). In the subset of patients with underlying cystic kidney disease and in hemodialysis patients treated with recombinant human EPO, hemoglobin, hematocrit and EPO levels were higher when compared to hemodialysis or CAPD patients with other kidney diseases. Following successful renal transplantation, EPO increased to 45 +/- 31 mU/ml at 1 month and then decreased to 25 +/- 18, 18 +/- 7 and 19 +/- 4 mU/ml at 3,6 and 9 months, respectively. Within the 1st month after transplantation there was a 4-fold increase in reticulocytes from 9 +/- 5 to 38 +/- 14%, followed by a slow decrease over the next several months to 23 +/- 11% at 9 months. In contrast, the hematocrit level rose more gradually from 28 +/- 7 to 44 +/- 6% at 9 months. In 25 of 36 patients with a functioning graft who were followed for more than 6 months, anemia was corrected and 11 patients remained slightly anemic with a mean hematocrit level of 36 +/- 4%.
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.