Nurol Arik

Subclinical Adrenocortical Insufficiency in Renal Amyloidosis

In order to investigate the functional significance of possible adrenal amyloid infiltration in patients with renal amyloidosis, we performed corticotrophin stimulation tests in 15 patients having renal amyloidosis with no clinical evidence of adrenocortical insufficiency and 12 controls. In 7 of the patients, the cortisol increments obtained during the test were found to be consistent with primary adrenal insufficiency due to possible amyloid infiltration of the adrenal cortex; in contrast, in all control subjects, adrenal responses to the test were regarded as sufficient for proper adrenal function.

Sudden Hearing Loss in a Cyclosporin-Treated Renal Transplantation Patient

Turgay Arinsoy, Nephrology and Otolaryngology Departments, Hacettepe University Medical School, T-06100 Ankara (Turkey) Sir, Thromboembolic complications constitute an important risk in the postoperative course after renal transplantation. The incidence has been reported to be as high as 24% [1]. We present a case of sudden hearing loss due to a thromboembolic event in a renal transplant recipient on triple immunosup-pressive treatment consisting of cyclosporin A (CsA), azathioprine (Aza) and predniso-lone (Pred). A 22-year-old Caucasian male with end-stage renal disease secondary to membrano-proliferative glomerulonephritis underwent a living-related donor renal transplantation. The patient had been maintained on a hemo-dialysis program for 3 months prior to renal transplantation. Initial laboratory results showed that serum creatinine level and blood urea nitrogen were 397 μmol/l and 18.3 mmol/l, respectively. The remainder of his laboratory results including prothrombin time (FT), partial thromboplastin time (PTT), chest X-ray and electrocardiogram were within normal limits. Before the operation, CsA was given in a single dose of 4 mg/kg orally. Methylpredni-solone 1,000 mg and Aza 150 mg were given intravenously during surgery. On the operation day, Pred 100 mg was given orally and tapered by 10 mg daily until the dose of 20 mg per day. He received CsA (4 mg/kg) b.i.d. and Aza (1.5 mg/kg/day) in a single oral dose. He tolerated the operation well and had good urine output postoperatively. On the 7th postoperative day, the patient complained of right sudden hearing loss. On the same day, his blood CsA level was measured as 200 ng/ml, and serum creatinine level was 106 μmol/l. PT and PTT were within normal limits. Because of right sudden hearing loss, the patient was referred to the Otolaryngology Department. He had not any vestibular symptoms, otolaryngologic examination revealed no abnormality except for tuning fork tests. With the tuning fork at 512 cps, there was no response on the right ear. The patient localized the sound in the left ear on the Weber test. Investigations included a full range of

Reversible Neutropenia and Thrombocytopenia during Famotidine Treatment

I. Gelenberg AJ. Sertraline-MAOI interaction. Bioi Ther Psychiatry 1993; 16(7). 2. Iacono R, Toyama S, Meltzer C. The use of selective serotonin reuptake inhibitors (SSRI) in the treatment of Parkinsons disease. Submitted to the 11th International Meeting on Parkinsons Disease. Rome, Italy: March 1994. 3. Tohgi H, Abe T, Takahashi S, Takahashi J, Hamato H. Concentrations of serotonin and its related substances in the cerebrospinal fluid of parkinsonian patients and their relations to the severity of symptoms. Neurosci Lett 1993;150:71-4. 4. Wesemann W, Clement H, Grote C, Functional studies on monoaminergic transmitter release in parkinsonism. Clin Neuropharmacol 1990; 13(2):11-5-3. 5. Halliday GM, Li Y.W, B1umbey PC, et aI. Neuropathology of irnmunohistochemically identified brain stem neurons in Parkinsons disease. Ann NeuroI1990;27:373-85. 6. Baldessarini RJ, Cedarbaum JM, Schleifer LS. In: Gilman AG, Rail TW, Nies AS, Taylor P, eds. Goodman and Gilmans the pharmacological basis of therapeutics 8th ed., New York: Pergamon Press, 1990: 384-435,463-484.

Hyperphosphatemia: A Serious Limiting Factor Preventing the Possible Benefit from Intravenous Calcitriol Therapy

Accessible online at: http://BioMedNet.com/karger Dear Sir, Uremic bone disease is a frequent and disabling complication of end-stage renal disease. Over the last decade, several studies have been published on the use of intravenous (IV) calcitriol therapy in the treatment of secondary hyperparathyroidism [1–3]. There remains some uncertainty on the optimum use of IV calcitriol therapy [4]. In this study, we evaluated the effect of long-term IV calcitriol therapy on the parameters that can be used in monitoring uremic bone disease activity such as parathyroid hormone (PTH), alkaline phosphatase (AP) and bone mineral density (BMD) in 8 uremic patients with secondary hyperparathyroidism. Eight uremic patients with secondary hyperparathyroidism on chronic hemodialysis were selected for the study. After the baseline data had been collected, intravenous calcitriol (Calcijex®, Abbott Lab, Chicago, Ill, USA) was administered at the end of each dialysis session. The initial dose was 0.5 Ìg per injection and it was increased in 0.5-Ìg increments to a maximum tolerable dose. The duration of study was 12 months. The levels of intact PTH and AP, and BMD density in different locations were measured before and after 12 months’ therapy with IV calcitriol in all patients. IV calcitriol was temporarily discontinued or its dosage reduced if the serum calcium and phosphorus concentrations exceeded 11.5 and 6.5 mg/dl, respectively, or the calcium-phosphorus product was greater than 70. A dual energy X-ray bone densitometer was used to measure BMD. Regional BMD values were obtained for the lumbar spine [L3 (BMD), L2– L3 (BMD2)], for proximal portions of both femurs [femoral neck (BMD3), femoral trochanter (BMD4), Ward’s triangle (BMD5)]. Right/left average values of femoral measurements were taken for the analysis. In the present study, the numbers of the observed episodes of hyperphosphatemia and hypercalcemia were 37 and 2, respectively. In 5 of these episodes, increased calcium-phosphorus product values were also noted. Because of the frequent episodes of hyperphosphatemia, hypercalcemia, and increased calcium-phosphorus product, IV calcitriol dose could not exceed 2 Ìg/dialysis session on a regular basis in the participating patients. The mean calcitriol dose was 0.92 Ìg/dialysis session throughout the study. The determined changes in biochemical parameters and bone mineral density values during therapy are shown in table 1. As shown in table 1, we could not determine any significant changes in measured parameters after calcitriol therapy in this study. Although several studies have been published on the use of IV calcitriol therapy, the optimal dosage regimen has not yet been clarified [1–3]. But, in general, a dose greater than 2 Ìg/dialysis has been found to be more efficient than one less than 1 Ìg/dialysis [4]. In the present study, the mean calcitriol dose/dialysis session was found to be 0.92 Ìg. Undoubtedly, other factors unrelated with the calcitriol dose might have contributed to the therapy failure in our patients; we think that our failure both to decrease the PTH and AP levels and to improve BMD must be due to our inability to use an effective dose of IV calcitriol. The major limiting factor preventing the use of an effective dose of IV calcitriol in our

Horizontal Transmission of Hepatitis C Virus to the Spouses of Patients on Renal Replacement Therapy

Dr. Oktay Oymak, Hacettepe University School of Medicine, Department of Nephrology, TR-06100 Ankara (Turkey) Dear Sir, Hepatitis C virus (HCV) is the most common cause of hepatitis in hemodialysis patients and renal transplant recipients. The major transmission routes of HCV infections are blood transfusions and inoculations; furthermore, organ transplantation, vertical and heterosexual transmission have also been documented [1]. In order to evaluate the contribution of end-stage renal disease patients on renal replacement therapy to the spread of HCV infection, we investigated HCV antibody (anti-HCV) and serum alanine amino-transferase levels in the spouses of these patients. Eighty patients on renal replacement therapy (table 1) and their spouses (28 males, 52 females, aged 37.1 years, range 23-62) and 30 controls (16 males, 14 females, aged 41.5 years, range 2665) were included in the study. 65 of the 80 patients on renal replacement therapy were sexually active. Anti-HCV was measured by a 2nd-generation enzyme-linked immunosorbent assay to C100-3 and 33c antigens of HCV(ELISA, Abbott). Four of the 80 spouses of the patients on renal replacement therapy were anti-HCV positive and none of the controls were anti-HCV positive. The characteristics of these 4 partners were as follows: (1) 3 of them were female and 1 of them was male with a median age of 37.8 years (range 31^45); (2) all their partners were in the anti-HCV-positive group (3 renal transplanted and 1 hemodialysis patients); (3) they did not share any risk factor including blood transfusion for HCV infection; (4) 3 of the patients as well as 2 of their spouses had raised serum alanine aminotransferase levels; (5) all of these pairs were sexually active and they were not using condoms during intercourse. Although there are contrary studies [2], many reports have shown higher anti-HCV Table 1. Characteristics of patients on renal replacement therapy (means and range) Hemodialysis patients Transplanted patients

HIGH PREVALENCE OF ANTIBODIES TO HEPATITIS C VIRUS AMONG RENAL TRANSPLANT RECIPIENTS : CORRELATION WITH CHRONIC LIVER DYSFUNCTION

Dr. Tekin Akpolat, Hacettepe Hastanesi, Nefroloji Bölümü, Hacettepe, TR-06100 Ankara (Turkey) Dear Sir, Chronic liver disease is a frequent and major complication in renal transplant recipients and contributes greatly to morbidity and mortality in these patients [1]. Hepatitis C virus (HCV) is the most common cause of transplant-associated liver disease [1, 2]. Currently, assays are available to detect antibody to recombinant antigens of HCV (anti-HCV). The aim of our study was to evaluate the prevalence of anti-HCV among renal transplant patients and the possible correlations of anti-HCV with chronic liver dysfunction, graft survival, number of blood transfusions, hepatitis B virus serologic markers and duration of hemodialysis therapy before transplantation in this group of patients. One hundred and sixty-one patients (119 men and 42 women; mean age 35.6 years, range 18-65) were included in the study. Seventy of 161 patients were transplanted in our unit and the rest were referred from other centers for long-term follow-up. Anti-HCV was measured by a second-generation enzyme-linked immunosorbent assay to C100-3 and 33c antigens of HCV (ELISA, Abbott). Chronic liver dysfunction was considered to be a persistent elevation of the serum alanin aminotransferase levels for more than 6 months. Statistical analysis was performed by the χ2 test with Yates’ correction or Student’s test. Ninety-two of 161 patients (57.1%) were anti-HCV positive (table 1), and in the anti-HCVpositive group, the number of patients with chronic liver dysfunction was significantly higher and the duration of hemodialysis treatment was significantly longer than in the negative group. There was no significant difference between the two groups regarding the number of blood transfusions, graft survival and hepatitis B virus serologic markers. Preliminary surveys of renal transplant recipients have shown an anti-HCV prevalence ranging from 10 to 41% [2-5]. Anti-HCV was positive in 57.1% of patients in the present

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-

Acute effect of erythropoietin on catecholamine levels in uremia.

Tekin Akpolat, Hacettepe Hastanesi, Nefroloji Bölümü, Hacettepe, TR-06100 Ankara (Turkey) which time the baseline sample was withdrawn. After the baseline sampling at 8.00 a.m., rHuEPO was given intravenously at a dose of 75 U/kg. Blood samples for analysis were taken at 15, 30 and 60 min after the injection and blood pressure readings were recorded simultaneously. Serum ‚L·DOPA, dopamine, norepinephrine and epinephrine levels were measured by highperformance liquid chromatography with electrochemical detection [6]. Student’s Dear Sir, Approximately one third of the patients treated with recombinant erythropoietin (r-HuEPO) will experience either an aggravation of preexisting hypertension or will develop de novo hypertension [1]. But the mechanism is unclear and various causes such as increased blood viscosity and total red cell mass inducing an increase in peripheral resistance [2] and reversal of compensatory va-sodilatation induced by renal anemia [3] have been proposed by several studies before. Besides, some investigators have suggested that r-HuEPO-induced alterations in sympathetic nervous system activity may contribute to the genesis of hypertension during r-HuEPO therapy [4, 5]. In order to clarify the relationship between r-HuEPO and sympathetic activity and determine whether r-HuEPO does have any direct effect on catecholamine levels, we studied serum concentrations of Í^DOPA, do-pamine, norepinephrine and epinephrine after a single dose of r-HuEPO administration in 12 predialysis uremic patients. We included 12 patients with chronic renal failure untreated by dialysis previously (mean age 34.0 years, range 21-68; 5 females and 7 males). The patients had never taken r-HuEPO before and all medications having influence on the sympathetic activity were discontinued 2 weeks before the test. Since catecholamine levels are affected by position,

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

Acute Effect of Erythropoietin on Plasma Renin Activity and Aldosterone Levels in End-Stage Renal Disease

Dr. Nurol Arik, Hacettepe Hastanesi, Nefroloji Bölümü, TR-06100 Hacettepe-Ankara (Turkey) Dear Sir, Approximately one third of the patients treated with recombinant human erythropoietin (rhEPO) will experience either an aggravation of preexisting hypertension or will develop de novo hypertension [1]. But the underlying mechanism is unclear and various causes such as the increased blood viscosity and total red cell mass inducing an increase in peripheral resistance [2] and the reversal of compensatory vasodilatation induced by renal anemia [3] have been proposed by several studies before. Besides, some investigators have suggested that rhEPO itself has some effect on renin-angiotensin-aldosterone axis. So, it has been proposed that the alterations in this axis may contribute to the changes in blood pressure during rhEPO treatment [4,5]. In order to clarify the acute effect of rhEPO on plasma renin activity (PRA) and aldosterone secretion, we studied PRA and aldosterone levels after rhEPO injection in 9 predial-ysis uremic patients. We included 9 patients with chronic renal failure, untreated by dialysis previously. The patients had never taken rhEPO, antihyper-tensives, and the drugs affecting the renin-angiotensin axis and aldosterone secretion such as aldosterone antagonists and angiotensinconverting enzyme inhibitors. Patients were maintained at bedrest in supine position for 6 h prior to rhEPO injection and they kept their supine position throughout the test. After the baseline sampling at 8.00 a.m. rhEPO was given intravenously at a dose of 50 U/kg. Blood samples for analysis were taken at 15, 30 and 60 min after injection and blood pressures were recorded simultaneously. 7-ι ε < o. 3