Şali Çağlar

Radiocontrast-induced nephrotoxicity and urinary alpha-glutathione S-transferase levels: Effect of amlodipine administration

Aims: The exact pathogenesis and prophylaxis concerning radiocontrast-induced nephrotoxicity (RCIN) was unclear. Short-acting calcium antagonists were used to prevent RCIN. This study was designed to evaluate the role of a long-acting calcium antagonist (amlodipine) administration by determining serum creatinine (SCre) levels and 24 hour urinary excretion rates of glutathione S-transferase alpha (GST-α) which has a selective localization only to proximal tubular epithelium.Methods: In a prospective trial, 29 outpatients (19 M, 10 F) undergoing coronary angiography were randomized and either amlodipine 10 mg/day (n = 15) or placebo (n = 14) were administered prior to angiography and continued thereafter. All patients had normal basal renal function and none of them had any risk factor for RCIN. A low osmolar, nonionic contrast media (iopamidol 76%) was administered to all patients. Creatinine clearance (CCre), SCre and 24-hour urinary GST-α levels were measured before, 24 hours and 7 days after angiography.Results: SCre and 24 hour urinary GST-α values increased on 24th hour following the angiography in both groups (p < 0.017 and 0.001, respectively). Pretreatment with amlodipine created no difference in both variables (p > 0.05).Conclusions: A reversible tubular dysfunction occurs following radiocontrast administration which was manifested by an increase in urinary GST-α excretion rates. Pretreatment with a long acting calcium antagonist amlodipine has no effect on the course of enzyme excretion and alteration observed in SCre

Nonrelated Living-Donor Kidney Transplantation: Medical and Ethical Aspects

Several patients with end-stage renal disease went to Bombay for renal transplantation from nonrelated living donors and then returned to Turkey for posttransplantation follow-up. The aims of this study are to evaluate the long-term results of renal transplantation from nonrelated living donors in Turkish patients with end-stage renal disease and to discuss the ethical and social aspects of nonrelated kidney donation. One hundred and twenty-seven patients (89 males, 38 females; mean age 38.1, range 17–63 years) were investigated retrospectively. None of the patients went to Bombay on our advice. All transplantations were performed between 1991 and 1995. The mean follow-up period after transplantation was 34.2 (range 1–68) months. Graft survival rates were 85, 83, and 57% after 3 months and 1 and 5 years, respectively. Patient survival rates were 94, 93, and 92% after 3 months and 1 and 5 years, respectively. Seven patients died within the first 3 months after the transplantation. Surgical problems, infections, acute rejection, ciclosporin nephrotoxicity, and hepatic problems were common complications. We conclude that medical and surgical complications occur frequently in paid kidney transplantation, but most of these complications can be prevented by adequate preoperative management, and precautionary measures should be taken to prevent commercialization of renal transplantation before the spread of emotionally related living kidney donation.

Association between activated renin angiotensin system and bone formation in hemodialysis patients: is the bone mass genetically determined by ACE gene polymorphism?

Background. Angiotensin II (ang II) receptor subtype I binding sites has been recently demonstrated on bone cell precursors. Ang II stimulates DNA and collagen synthesis in human adult bone cells. The aim of this study is to evaluate the role of renin angiotensin system in the bone metabolism and to address the genetic influence of angiotensin converting enzyme (ACE) gene polymorphism on bone mass in hemodialysis patients. Methods. Forty‐eight end‐stage renal disease patients (28 male, 20 female mean age 42 ± 13 years,) on maintenance hemodialysis were included in the study. Bone mineral density (BMD) was estimated at lumbar spine and T score worse than − 1.5 were considered as osteopenia. Serum parathyroid hormone (iPTH) and osteocalcin (OC), bone alkaline phosphatase (bAP) and carboxy terminal propeptide type 1 collagen (PICP) levels were measured as markers of bone metabolism. Plasma renin activity (PRA), serum ACE activity and ACE gene polymorphism (II, ID, DD) were determined. Results. Bone mineral density and T score of the hemodialysis patients were 0.92 ± 0.17 g/cm2 and − 1.36 ± 1.50, respectively. Twenty‐one patients (43,7%) were osteopenic (T score worse than − 1.5) and mean T score of osteopenic patients was − 2.72 ± 0.72. T score of nonosteopenic group was − 0.29 ± 0.99. Serum calcium, serum, phosphorus, serum OC, serum bAP, serum PCIP, serum PTH levels were similar in osteopenics and nonosteopenics. No difference was observed in predialysis PRA and in both pre‐ and postdialysis serum ACE activity of patients in both groups. PRA after hemodialysis in nonosteopenic group was higher than osteopenics (p < 0.05). Percent increment in PRA in hemodialysis patients was correlated with T score (R = 0.48 p < 0.05). Serum ACE activity was positively correlated with serum iPTH (R = 0.29, p = 0.02), serum OC (R = 0.35, p = 0.01), serum bAP (R = 0.34, p = 0.01), serum PCIP (R = 0.36, p = 0.01). T score (− 0.7 ± 1.5, vs − 1.7 ± 1.3 p < 0.05) was higher in DD group (n = 19) compared to II + ID group (n = 29). Conclusions. Association of biochemical and radiological signs of increased bone formation with activated RAS in hemodialysis patients might be an evidence for the involvement of this system in the regulation of bone metabolism.

Primary Hyperparathyroidism in a Patient with Systemic Lupus erythematosus-Antiphospholipid Syndrome

This article is also accessible online at: http://BioMedNet.com/karger Dear Sir, Primary hyperparathyroidism is a metabolic disorder resulting from excessive production of parathyroid hormone (PTH) and probably is the most common cause of hypercalcaemia in the general population [1]. Primary hyperparathyroidism is presented in a patient with impending renal failure due to systemic lupus erythematosus with antiphospholipid syndrome (SLE-aPLS). To the best of our knowledge, primary hyperparathyroidism associated with SLE-aPLS has not been previously reported. A 42-year-old woman was hospitalized in January 1995 because of extreme weakness, advanced osteoporosis with pathological fractures, and impending renal failure. Ten years earlier, SLE had been diagnosed at another center on the basis of facial erythema, Raynaud phenomenon, polyarthritis, temporal lobe epilepsy, and positive antinuclear antibody and anti-dsDNA tests. She had been given corticosteroids for about 5 years and azathioprine for less than 1 year. In response to this treatment, her symptoms had resolved, and the steroid dose had been tapered without a recurrence. In her medical history, she had three spontaneous fetal losses, two pregnancies with intrauterine fetal death at the 8th month, and one miscarriage at the 3rd month. She also had a temporary loss of vision 3 years previously which resolved within 1 week. She was hypertensive, but other physical examination findings were normal. Laboratory investigations disclosed the following values: hemoglobin 8.3 g/dl, platelets 91 ! 109/l, calcium 10.4 mg/dl, phosphate 1.9, blood urea nitrogen 31, creatinine 2.8 mg/dl, albumin 3.7 g/dl, and alkaline phosphatase 1,352 U/l. She had a proteinuria of 2 g/day and a creatinine clearance of 9 ml/min. The antinuclear antibody level was 190 U/ml

Effects of Nitrendipine on Blood Pressure and Blood Ciclosporin A Level in Patients with Posttransplant Hypertension

In order to evaluate the antihypertensive effectiveness and interaction with ciclosporin A (CS-A) nitrendipine, a dihydropyridine derivative calcium entry blocking agent, was used in 16 (13 men, 3 women) hypertensive renal posttransplant patients followed by the Nephrology Department of Hacettepe University Hospital. The patients did not receive any antihypertensive drug for a 7-day period. They were then given 20 mg/day nitrendipine for 3 weeks. At the end of this period, mean (+/- SE) supine blood pressure fell from 163/108 +/- 3.6/1.87 to 141/87 +/- 3.8/2.2 mm Hg (p less than 0.01), while the heart rate was unchanged. 14 of 16 patients achieved full control of blood pressure levels with 20 mg/day nitrendipine, and only 2 patients needed a higher dosage of 30 mg/day (20 + 10 mg). After 3 weeks of treatment no significant variations in blood chemistry or renal functional parameters were noticed. There was also no difference between blood CS-A levels before and after treatment with nitrendipine (218.06 +/- 33 vs. 222.68 +/- 26 ng/ml, p greater than 0.05). We conclude that short-term therapy with nitrendipine in renal post-transplant patients does not appear to be harmful and longer term studies are needed to fully evaluate safety and efficacy of this drug. Because it influences neither blood chemistry nor renal functional parameters and blood CS-A level, it may be preferable to other calcium channel blocking agents in this group of patients.

Local Fibrinolysis in Native Arteriovenous Fistulas of Haemodialysis Patients

This study was designed to evaluate local alterations of the fibrinolytic process in patent-functional native arteriovenous fistulas of patients on maintenance haemodialysis. For this aim, the concentrations of the main components of the fibrinolytic system were determined in plasma samples taken simultaneously from arteriovenous fistulas and contralateral upper extremity concurrent large veins of haemodialysis patients. Twelve patients (6 women and 6 men, age 36 +/- 8 years) with end-stage renal disease on maintenance haemodialysis and 15 non-smoker healthy volunteers (8 women and 7 men, age 31 +/- 10 years) with normal renal function were included in the study. The fibrinolytic parameters, except alpha 2-antiplasmin, were found to be elevated in arteriovenous fistulas of haemodialysis patients as compared with opposite upper extremity large veins of the same patients (p < 0.005). Increments in fibrinolytic parameters including tissue plasminogen activator antigen, urokinase-type plasminogen activator antigen and activity, and plasminogen activity together with lower alpha 2-antiplasmin levels favor activation of fibrinolysis, except for higher alpha 2-macroglobulin concentrations, in arteriovenous fistula. The study suggests that the fibrinolytic process is locally activated in arteriovenous fistulas of haemodialysis patients.

Mediastinal Hematoma: A Rare Complication of Subclavian Catheterization for Hemodialysis

Dr. Nurol Arik, Hacettepe Hastanesi Nefroloji Bölümü, TR-06100 Hacettepe-Ankara, (Turkey) Fig. 1a, b CT scans of the thorax demonstrating a large mediastinal hematoma (H). Dear Sir, Subclavian vein catheterization was first introduced in the late 1970s and has become a preferred method of temporary vascular access for acute hemodialysis. Now, it is widely used all over the world. However, acute complications such as hemothorax, pneumotho-rax, atrial perforation, air embolism and delayed complications such as stenosis and bac-teremia associated with the placement of catheters continue to occur [1]. This report describes a rare complication of subclavian catheter insertion for hemodialysis in a patient with end-stage renal failure. A 51 -year-old man with chronic renal failure was started on chronic hemodialysis in July 1986. He underwent cadaveric renal transplantation in November 1989. As a result of graft loss due to chronic rejection, the patient returned to a hemodialysis program by arteriovenous fistula which was formed at the wrist in his left arm in June 1990. He had been hospitalized because of fistula occlusion, and a new fistula was created at the wrist in his right arm on December 7, 1991. While awaiting the maturation of the new fistula, he developed symptoms of hypervolemia. So, it was decided to place a subclavian hemodialysis catheter for immediate access. Before the placement of the catheter, a chest x-ray was taken and showed no abnormality except for cardiac enlargement present on previous radiographs. A doublelumen hemodialysis catheter was inserted via the left subclavian vein using the Seldinger technique. Following the procedure the patient complained about shortness of breath; subsequently dyspnea increased, and orthopnea appeared within a few hours after the insertion of the catheter. A marked reduction of blood pressure was recorded as well. A postinsertion chest x-ray revealed a large opacity covering the media-

Pure Red Cell Aplasia Preceding Malignant Lymphoma in a Renal Transplant Patient

Malignant disorders are one of the major causes of morbidity and mortality in transplant patients. We present herein a renal transplant recipient with malignant lymphoma which preceded by pure red cell aplasia (PRCA). Acquired PRCA is a rare hematologic disorder in renal transplant recipients. It has been associated with a variety of disorders of immunologic dysfunction and neoplasms, exposure to drugs and toxins, infectious diseases, pregnancy and severe nutritional deficiency. This is the first case with PRCA preceding the malign lymphoma in a renal transplant patient. Treatment of lymphoma and lymphoma-related humoral and cellular changes or other undefined effects that may be related to therapy may be responsible of the resolving of PRCA in this patient. In this regard, renal transplant patients with acquired PRCA, must be closely followed for an underlying neoplastic disorder.

Coagulation and Fibrinolysis in Amyloid and Non-amyloid Hemodialysis Patients: Assessment of Local Hemostatic Kinetics Within Arteriovenous Fistulas

This study was designed to determine whether systemic amyloidosis is an additional risk factor for he mostatic abnormalities in hemodialysis patients and to evaluate local alterations of the hemostatic process within the patent-functional native arteriovenous fistula (AVF). Concentrations of in vivo molecular hemostatic markers, including prothrombin fragment1 +2 (PF 1.2), thrombin antithrombin III complex (TAT) and plasmin-α 2 antiplasmin complex (PAP) were determined in plasma samples taken simultaneously from AVFs and contralat eral upper extremity large veins of hemodialysis patients associated with and without systemic amyloidosis. Seven amyloid (2 women, 5 men, aged 34 ± 6 years), and 13 non-amyloid patients (4 women, 9 men, aged 36 ± 7 years) on maintenance hemodialysis and 20 healthy vol unteers (8 women, 12 men, aged 36 ± 9 years) were in cluded in the study. Peripheral vein PF 1.2 and TAT lev els showed no difference between amyloid and non- amyloid patient groups, but both were significantly higher than control group. PF 1.2 and TAT levels were also found to be elevated in fistulas when compared with that of peripheral vein in both amyloid and non-amyloid pa tient groups. Determination of PAP in peripheral veins of each group revealed significantly higher levels in amyloid hemodialysis patients than in non-amyloid patients and controls. PAP levels were significantly higher in fistulas of amyloid patients than in non-amyloid patients. In con clusion, this study confirms enhanced coagulation and fibrinolysis in hemodialysis patients and excessive fibri nolysis in amyloid patients with remarkable contribu tion of AVF on enhanced coagulation and fibrinolysis.

Protein C and Its Inhibitors during Hemodialysis

Dr. Nurol Arik, Hacettepe Hastanesi, Nefroloji Bölümü, TR-06100 Hacettepe-Ankara (Turkey) Table 1. Mean values of PCA, PAI-3 and αr AT levels in hemodialysis patients and controls Before dialysis After dialysis Controls PCA, % PAI-3,% αrAT, mg/dl 60.5 + 9.9 84.2 + 5.8 217.3 + 8.8 Means ± SEM. 1 Corrected for changes in Hct. Dear Sir, Low anticoagulant activity of protein C in uremia has been reported previously, and it was suggested that this may contribute to the prethrombotic state observed in these patients [1]. On the other hand, Knudsen et al. [2] had shown that protein C activity (PCA) increased acutely during hemodialysis, the underlying mechanism, however, was unclear, and they had speculated the presence of an unknown dialyzable inhibitor of protein C in uremic plasma. In order to clarify the role of protein C inhibitors in the genesis of protein C changes during hemodialysis, we studied the two well-known protein C inhibitors, namely, plasminogen activator inhibitor-3 (PAI-3) and αrantitrypsin (α‚-AT) [3, 4] besides PCA before and after hemodialysis in uremic patients on regular dialysis. 18 healthy controls and 20 patients with end-stage renal failure were studied. All patients were on regular hemodialysis performed for 4-6 h 2 or 3 times a week. Following dialysis, αrAT levels were corrected for the changes in Hct. Hct correction factor was calculated from the quotient (100-HctpOSt)/(100-Hctpre). The mean values of PCA, PAI-3 and α‚AT levels in 20 patients and 18 controls are presented in table 1. Mean PCA before dialysis was found to be lower in the uremic group than in the control group (p < 0.05) and increased significantly after dialysis compared with predialysis values (p < 0.02). Hemodialysis induced statistically significant increases in PAI3 activity as well (p < 0.02). The observed significant increase in the mean α‚-AT level (p < 0.05) was considered to be due to volume contraction caused by the hemodialysis procedure