Celalettin Usalan

Effects of angiotensin converting enzyme and angiotensin II receptor inhibition on impaired fibrinolysis in systemic hypertension

Abnormalities in fibrinolysis have been reported in hypertension. Angiotensin converting enzyme (ACE) inhibitors have been shown to improve altered fibrinolytic balance in hypertensive patients. It has not been documented, however, whether this is due to a decrease in angiotensin II (Ang-II) generation or is a consequence of elevated local levels of bradykinin. Accordingly, the aim of this study was to determine the effects of an ACE inhibitor (perindopril) and an Ang-II receptor antagonist (losartan) on fibrinolytic kinetics. We have examined the serum levels of the plasminogen activator inhibitor type-1 (PAI-1) antigen and activity, tissue plasminogen activator (t-PA) antigen and activity, soluble thrombomodulin (sTM), and tissue factor pathway inhibitor (TFPI) before and after reaching the target blood pressure (<140/90 mm Hg) in 13 hypertensive patients receiving perindopril (mean age 40+/-11 years, 6 women, 7 men) and in 12 patients receiving losartan (mean age 38+/-9 years, 6 women, 6 men). We also compared the baseline fibrinolytic activity of hypertensive patients with that of 12 normotensive control persons (mean age 40+/-9 years, 6 women, 6 men). The mean basal plasma levels of PAI-1 antigen, PAI-1 activity, and sTM were significantly higher in the hypertensive patients than in normal controls (P<.005). The values of other analytes were similar in both groups. Increased plasma levels of PAI-1 antigen, PAI-1 activity, and sTM were reduced in patients after they were given perindopril and losartan (P<.005); the reductions in losartan-receiving group were more pronounced (P<.05). There were no significant effects on the plasma levels of t-PA antigen, t-PA activity, and TFPI in patients receiving the two therapeutic regimens (P>.05). In conclusion, chronic hypertension is associated with hypofibrinolysis. The beneficial effect of ACE inhibitors on fibrinolysis seems to be related to the blockade of Ang-II, and increased kinin activity does not appear to play a major role.

Membranoproliferative glomerulonephritis associated with small cell lung carcinoma

An association between nephropathy and malignant solid tumours or with lymphoproliferative disorders was repeatedly reported. This association is mainly manifested by a nephrotic syndrome. In Lees study [14], 11% of the adult nephrotics whom they had seen over a ten-year period developed a carcinoma. Membranous glomerulonephritis (MGN) is the most common glomerular disease associated with malignant solid tumour; the association of membranoproliferative glomerulonephritis (MPGN) with solid tumour is still uncommon. Although lung carcinoma is relatively common, the incidence of glomerular involvement with this tumour is quite rare. To date, only a few cases of lung cancer associated with nephrotic syndrome or glomerulonephritis have been reported by various authors. MGN is the most common glomerular lesion associated with these cases; however, MPGN has not been reported to be associated with lung cancer before. We report on a 45-year old man with nephrotic syndrome due to MPGN which in this case seemed to be a component of the paraneoplastic syndrome.

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

THE BOOSTER PHENOMENON IN 2-STEP TUBERCULIN SKIN TESTING OF PATIENTS RECEIVING LONG TERM HEMODIALYSIS

BACKGROUND Tuberculosis remains a significant health problem for patients receiving long-term hemodialysis (HD). The tuberculin skin test (TST) is an important method for detecting Mycobacterium tuberculosis infection. This study examined the significance and frequency of the booster phenomenon in serial TST of HD patients. METHOD Fifty-three outpatients in a hospital-based HD center in Turkey were screened for tuberculosis with the TST between August and October 1999. To determine the frequency of booster phenomenon, patients with less than 10 mm indurations to the initial TST were given a second test 7 days later. RESULTS Nineteen (35.8%) of 53 patients had a significant tuberculin reaction (> or = 10 mm) on the initial TST. The booster effect was detected in 10 (29.4%) of 34 patients who had a negative reaction (< 10 mm) to the initial test. Overall, 29 (54.7%) patients showed a significant reaction on both tests. CONCLUSIONS These results showed significant rates of TST positivity and the booster effect in this HD center.

Protein Z Levels in Haemodialysis Patients

Protein Z (PZ) is a vitamin K-dependent protein isolated from human and bovine plasmas. Although the exact role of PZ in the haemostatic system is presently unknown, it is suggested that PZ deficiency may cause bleeding tendency. Haemostatic alterations in end-stage renal failure (ESRF) are certainly complex and involve several abnormalities in the coagulation and fibrinolytic system. In order to elucidate the detail of the haemostasis in ESRF, we aimed to investigate PZ activity in haemodialysis patients.Therefore, we compared plasma PZ levels in 10 haemodialysis patients (6M, 4 F, mean age 36±11) and 10 healthy normal controls (5 M, 5 F, mean age 34±8) in this study. We found mean plasma PZ levels in haemodialysis patients and healthy controls 6.95±2.93 µg/ml and 3.06±0.81 µg/ml, respectively (p<0.005). Increased level of PZ which influences the action of thrombin on its protein substrates and inhibitors may contribute to the haemostatis alterations in ESRF patients, in addition to other well known abnormalities in the coagulation and fibrinolytic system.

Compliance in Hemodialysis Patients: Unanticipated Monitoring of Biochemical Indices

Compliance with the prescribed medical regimen is a critical factor for the continued well-being of hemodialysis patients. As compliance is a multifactorial problem, numerous approaches have been utilized to quantify the compliance of hemodialysis patients. In the present study, we have attempted to examine whether unanticipated control of biochemical indices might predict the compliance status of hemodialysis patients. We compared unanticipated mid-month values of blood urea nitrogen (BUN), serum potassium (K) and phosphate (PO4) values of 54 maintenance hemodialysis patients with the scheduled, regular first-week measurements during a 6-month study period. The interdialytic weight gain (IWG) levels of the corresponding weeks were also compared. Mid-month analysis revealed a significant deviation in the compliance status of the study population as BUN, serum K and IWGs were concerned (p < 0.05). The mid-month serum PO4 levels were also higher but the difference was not significant (p < 0.05). In conclusion, the differences observed in biochemical indices upon change of test request timing were distinctive. It suggests that unanticipated control of biochemical indices might contribute to the actual assessment of compliance in hemodialysis patients.

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.

Haemodialysis hypotension and nitric oxide production: comparison of heparin with parnaparin.

Background: There is increasing evidence for the role of nitric oxide (NO) in haemodialysis hypotension but the source of elevated NO is still controversial. Heparin has been reported to enhance NO production by cultured human endothelial cells. The aim of this study was to compare the role of unfractionated heparin and low molecular weight heparin (LMWH, parnaparin) on mean arterial pressure (MAP) and NO production in haemodialysis patients with hypotensive episodes. Patients and Methods: Ten maintenance haemodialysis patients with hypotensive episodes were involved in this study. Patients were anticoagulated with heparin for 3 weeks and then switched to parnaparin for 3 weeks. Serum NO levels were analysed before starting dialysis, at the nadir of MAP during a haemodialysis session and at the end of dialysis in the last haemodialysis session of the 3rd week of each anticoagulation treatment. Results: NO levels were 39.4 ± 13.2 µM at the beginning of haemodialysis, 92.4 ± 31.4 µM during hypotensive episode and 43.1 ± 25.1 µM at the end of dialysis with heparin treatment (p < 0.05). In the parnaparin period, NO levels were 47.2 ± 22.7 µM at the beginning, 80.7 ± 46.5 µM during the hypotensive episode and 45.8 ± 23.2 µM at the end of the session (p < 0.05). The percent increase in NO levels during the hypotensive period compared to that at the beginning of haemodialysis with heparin was significantly higher than that with parnaparin (140.2 ± 50.4 vs. 119.6 ± 44.8%; p < 0.05). The percent decrease in MAP with heparin use was also significantly higher than with parnaparin use (48.6 ± 6.4 vs. 39.6 ± 5.3%; p < 0.05). Conclusion: We have observed that MAP decrements and NO increases were less manifest during hypotensive episodes with parnaparin treatment compared to heparin. This difference may be related to differences in endothelial binding capacity, thrombin affinity and/or effects on platelet functions of unfractionated heparin and LMWHs.

Thrombopoietin and thrombospondin in renal allograft recipients.

Recipients of renal transplants appear to be at increased risk of thromboembolic events. Despite accumulating evidence for the hyperreactivity of platelets, the primary regulator of thrombopoiesis, thrombopoietin (TPO), has not yet been studied in renal transplant recipients. Thus, the aim of the present study was to quantify the levels of TPO and to assess its contribution to increased platelet reactivity in recipients of renal allografts. Serum concentrations of thrombospondin (TSP) were also determined in patients undergoing renal transplants in order to evaluate the role of this multifunctional protein in platelet hyperaggregability. Serum levels of TPO were significantly lower in renal transplant recipients (n = 27) than in healthy controls (30.8+/-20.6 pg/ml versus 129.9+/-113.6 pg/ml, P = 0.001). Serum concentrations of TPO were correlated neither with serum levels of creatinine nor duration of transplantation. However, levels of TPO were negatively correlated with platelet counts (r = -0.50, P = 0.007) in recipients of renal transplants. Plasma levels of TSP were higher in renal transplant patients than in the control group (104.5+/-54.7 ng/ml versus 63.4+/-41.5 ng/ml, P = 0.003). No significant correlation was found between levels of TPO and TSP. We conclude that, rather than the allograft function, the platelet mass determines the levels of TPO in recipients of renal transplants. Despite the low serum levels of TPO, and increased concentrations of TSP, TPO might still play a role in the hyperaggregability of platelets in patients undergoing renal transplants.

RAPIDLY PROGRESSIVE GLOMERULONEPHRITIS ASSOCIATED WITH PREGNANCY

Celalettin Usalan, MD, Sinan cad. 49/12, TR-6450 Dikmen, Ankara (Turkey) Dear Sir, Some diseases of the kidney are encountered in young women of childbearing age, and thus they may complicate pregnancy. In some cases, the diseases first appear during pregnancy, and in others renal function deteriorates rapidly and leads to maternal and fetal death [1]. Rapidly progressive glomerulonephritis (RPGN) is a rare cause of renal failure in association with pregnancy [1]. We report a patient with normal renal function and blood pressure and without proteinuria before pregnancy, whose renal function progressively deteriorated during pregnancy due to RPGN followed by spontaneous abortion. A 26-year-old woman who was now grav-ida 1 ‚ para 1 presented at 20 weeks’ gestation with malaise, cola-colored urine, decreased urine output and bilateral ankle edema. During the last 2 weeks, her edema increased and mounted to her legs. She had no history of renal disease. Her previous admission at 12 weeks’ gestation was not complicated by edema, hypertension or proteinuria. On her second admission at 20 weeks of gestation, blood pressure was 160/100 mm Hg. Physical examination was unremarkable except for bilateral ankle and leg edema. The results of urinalysis were specific gravity 1.016, pH 5,4+ protein, and urine sediment examination revealed red cell casts and fat bodies. She had 6.0 g protein in a 24hour urine collection. Complete blood count results were white blood cells 12,400/mm3, hemoglobin 10.2 g/dl and platelet count 256,000. Serum biochemistry results were as follows: BUN, 136mg/dl; creatinine, 12.6mg/dl; Na, 138 mEq/1; K, 6.2 mEq/1; Cl, 96 mEq/1. Total protein and albumin were 5.6 and 2.4 g/dl, respectively. Serum transaminases were within normal limits. The serum antinuclear antibody was negative. The serum anti-glomerular-basement-membrane and anti-neutrophilic-cytoplasm antibodies were also negative. The complement levels were within normal limits. Serological tests were negative for hepatitis B and hepatitis C. Abdominal ultrasonography showed mildly enlarged kidneys. Her condition worsened during the last 2 weeks and her pregnancy was complicated by spontaneous abortion. A renal biopsy was performed, and ‘crescentic glomerulonephritis without immune deposit’ was diagnosed. The patient was treated with intravenous pulse cyclosphosphamide (500 mg) and oral prednisolone (1 mg/kg/day), but the patient’s renal