Biomedical subjects
Publications and source records attributed to H Kopsa.
Nicotine abuse may cause severe nephrourologic diseases such as nephrosclerosis, hypertension and tumour of the bladder. The major factors for urinary tract diseases are hypoxaemia and cancerogenic substances. Aetiology and prophylaxis of malignant bladder tumour is discussed.
The clinical relevance of daily measurement of beta 2-microglobulin in serum and urine was evaluated in 49 patients undergoing renal transplantation. The changes in beta 2-microglobulin levels were compared to standard parameters for assessment of renal function. One hundred episodes of acute deterioration of renal function, clinically diagnosed as rejection, were analyzed retrospectively: (1) In 18 episodes renal malfunction did not respond to methylprednisone but improved immediately upon dose reduction of ciclosporin A, thus indicating a nephrotoxic effect of the drug. In these cases a mean increase of beta 2-microglobulin in urine as high as 7.9 mg/l was observed while serum values decreased. (2) Fifty episodes of apparent rejection (responsive to steroids) were preceded by a 3-day lasting continuous rise of beta 2-microglobulin in serum of up to 3.6 mg/l as a mean with only a moderate elevation in urine. (3) In 13 episodes antirejection treatment could have been avoided as continuously declining laboratory parameters indicated spontaneous improvement of renal function. We conclude that parallel determination of beta 2-microglobulin in serum and urine allows to differentiate between ciclosporin A nephrotoxicity and rejection in 91% of the cases.
Several lines of evidence suggest that tyrosine formation is impaired in renal failure. The concentration of tyrosine is decreased and the phenylalanine/tyrosine ratio is increased in plasma and in skeletal muscle cells. After an oral or intravenous load, the rise of plasma phenylalanine is augmented, the clearance is decreased, oxidation is diminished and the corresponding rise of plasma tyrosine level is blunted. Tyrosine elimination and oxidation are not altered in uremia. The defect in tyrosine formation may be especially important in uremic patients on a low protein diet supplemented with tyrosine-free essential amino acid preparations and in subjects on artificial nutritional support. Thus, tyrosine should be regarded as a conditionally essential amino acid in renal failure and should be supplied exogenously, at least in these patient groups. Oral tyrosine supplementation was shown to replete plasma and intracellular pools and improve nitrogen balance in chronic renal failure patients on a low protein diet. However, because of poor solubility in aqueous solutions, tyrosine cannot be included in the free form in amino acid solutions for parenteral nutrition. To circumvent stability or solubility problems, tyrosine containing dipeptides and/or N-acetyl-tyrosine may serve as tyrosine sources for parenteral supply. Renal failure does not affect alanyl-tyrosine hydrolysis, and there is an immediate increase of plasma tyrosine concentration after peptide infusion. Elimination and hydrolysis of glycine-tyrosine is retarded in renal failure, but the clearance exceeds clinically relevant infusion rates. After infusion of N-acetyl-tyrosine, no increase in plasma tyrosine is seen, and the half-life N-acetyl-tyrosine is grossly prolonged in uremia.(ABSTRACT TRUNCATED AT 250 WORDS)
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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.
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.
Secondary oxalosis in chronic hemodialyzed patients is caused by impaired renal excretion and inadequate removal of oxalic acid during hemodialysis. Ascorbic acid is a precursor of oxalic acid. We report a parathyroidectomized patient with chronic renal failure, on hemodialysis, who received over a period of several months a total dose of 91.0 g ascorbic acid i.v. The plasma oxalic acid level in this patient was 14-fold higher than in healthy persons. Increased oxalic acid synthesis from its precursor ascorbic acid may be responsible for hyperoxalemia, high content of oxalic acid in myocardium, aorta and lung, and calcium oxalate deposition in soft tissues. Application of high doses of ascorbic acid should be avoided in hemodialysed patients with chronic renal failure.
A prospective mammographic study was performed on 151 women to determine the prevalence of breast calcifications in patients with chronic renal failure. Frequency, size, structure, and location of calcific lesions were assessed in 15 patients with compensated renal insufficiency, 22 on hemodialysis, 14 who had renal transplants, and 100 who had normal kidney function. Serum levels of calcium, phosphorus, alkaline phosphatase, and parathyroid hormone were determined for all 151 women. The calcific lesions occurred preponderantly in dialysis patients (arteries, 55%; parenchyma, 68%; and ducts, 36%). Next in order were those with renal transplants (43%, 64%, and 29%, respectively) and those with renal insufficiency (33%, 53%, and 20%, respectively). Patients with renal disease had significantly more calcifications (p less than .001) than the patients with normal kidney function: arteries, 45% vs 8%; parenchyma, 61% vs 27%; and ducts, 29% vs 9%. Frequencies of calcifications correlated with serum levels of parathyroid hormone. None of the calcifications induced by renal disease simulated those seen in carcinoma of the breast.
Nephrotoxicity is the main side effect of cyclosporine therapy. In this study 2 groups consisting of 6 kidney transplant recipients were investigated. The oral cyclosporine daily dose was in the first group 13 mg/kg, in the second 11 mg/kg, respectively. In both groups, the daily dose was divided on the first day of investigation in 2 equal portions given at an interval of 12 hours. On the second day, the same dose was divided in 3 equal portions given at an interval of 8 hours. After cyclosporine administration twice a day very high blood cyclosporine peak concentrations (two to three times higher than the therapeutic range) were measured. These potential nephrotoxic cyclosporine concentrations could be prevented by cyclosporine application in 3 equal portions. A reduction of the daily dose in the early period after kidney transplantation to a starting daily dose of 12 mg/kg or even 10 mg/kg can be recommended.
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Cyclosporin A is an effective immunosuppressive substance which is extensively applied in various conditions. A well known side effect of high dose Cyclosporin A treatment is the occurrence of hypertrichosis, often referred to as hirsutism. The purpose of the study was therefore to investigate ovarian, adrenal and pituitary hormones as possible mediators of increased hair growth. In 5 female and 11 male patients who had developed hair overgrowth during Cyclosporin A treatment serum androgens (testosterone, dehydroepiandrosterone-sulfate, androstendione), sex hormone binding globuline (SHBG), prolactin (HPRL), 17-hydroxyprogesterone (17-OHP), 17 beta-estradiol (17 beta-E) and cortisol (F) were determined by standard radioimmunoassay methods. The same number of age matched patients with Azathioprine treatment served as control. Both patient groups received additive cortisone treatment of the same dosage. No significant differences of serum androgens were noted between Cyclosporin A treated patients and controls. In addition, normal prolactin levels were defected. 17-OHP was in the low normal range and cortisol below normal due to the additive cortisone treatment. SHBG was within normal range. The findings thus indicate that increased hair growth caused by Cyclosporin A seems not to be caused by an action of the substance on the hormonal level.
Sodium dodecyl sulphate (SDS) electrophoresis of urinary proteins was used routinely for monitoring more than 80 kidney transplant recipients as out-patients during one year. Special attention was paid to the question of whether this method can help the clinician to differentiate between a graft rejection reaction and Cyclosporin A-induced nephrotoxic damage. Two cases are presented showing the time course of proteinuric patterns together with serum creatinine, total urinary protein and, in one case, the blood level of Cyclosporin A. Changes of proteinuric patterns signalled the start of rejection and/or nephrotoxicity. A homogeneous collective of 33 kidney recipients (first transplantation) with chronic glomerulonephritis as a basic disease was specially selected. In this collective, the distribution of proteinuric patterns among patients and its dependence on immunosuppressive therapy was investigated. During the observation period of 7 months, two proteinuric patterns, "tubular" and "mixed weak", were found exclusively in Cyclosporin A-treated patients. We ascribe this finding to nephrotoxic effect of Cyclosporin A. We found the SDS electrophoresis of urinary proteins to be a useful, non-invasive method for monitoring Cyclosporin A-treated kidney transplant patients.
Factor XII, prekallikrein (PK) and high molecular weight kininogen (HMWK) clotting activities and antigen concentrations in kidney disease patients were studied. Chronic hemodialysis led to a reduction of F XII, PK and HMWK clotting activities. F XII and PK antigen levels were also low. In contrast, the HMWK antigen was normal with respect to concentration as well as electrophoretic migration behaviour on 2 D-immunelectrophoresis. In kidney transplant recipients more than three month after the transplantation, we found an increased of F XII and PK clotting activities, which appeared to depend on the time elapsed since the operation. However, the antigen levels remained normal. The group of chronic kidney disease patients not requiring hemodialysis exhibited normal mean values of all three clotting activities as well as normal F XII and HMWK antigen levels. The PK antigen was reduced. However, a separate evaluation of F XII clotting activities (F XII:C) in patients with glomerular nephritis showed elevated F XII:C which correlated with the BUN values. During acute processes of the kidney disease we observed very high PK clotting activities, which normalized with stabilization of the patients. Our results show that the contact phase coagulation factors behave abnormally in certain kidney disease patients.
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In nine patients with nephrotic syndrome the behaviour of plasma fibronectin was studied. Of nine patients seven showed elevated plasma fibronectin levels while the plasma fibrinogen level was increased in eight of the nine investigated patients. A positive correlation was found between plasma fibronectin levels and fibrinogen (P less than 0.01), cholesterol (P less than 0.01) and proteinuria (P less than 0.05). The results indicate that elevated plasma fibronectin levels could be an additional factor responsible for hypercoagulability in nephrotic syndrome.