Calcitriol Reduces Albuminuria and Urinary Angiotensinogen Level in Renal Transplant Recipients.

BACKGROUND: Although nonhuman animal models have strongly suggested that vitamin D suppresses the renin-angiotensin system (RAS) and albuminuria, human data are largely lacking. The aim of this study was to examine the relationship between 25-hydroxyvitamin D [25-(OH)D] level and albuminuria and urinary angiotensinogen (UAGT) level in renal transplant recipients (RTRs). We also planned to investigate the effect of calcitriol treatment on albuminuria and UAGT level in these patients. METHODS AND RESULTS: A total of 124 nondiabetic RTRs participated in this study. UAGT level was positively correlated with the urinary albumin-creatinine ratio (UACR) in all patients (r = 0.855; P < .001). The mean UACR (P = .036) and UAGT/urinary creatinine (UCr) level (P = .02) were significantly higher in RTRs with low 25-(OH)D than in RTRs with normal 25-(OH)D level. RTRs with low 25-(OH)D level were randomized to receive either 0.25 µg/d calcitriol (n = 40) or placebo (n = 40). All of the parameters were assessed again 12 months later in both groups. The mean UACR (P = .014) and UAGT/UCr level (P = .012) were significantly lower in the calcitriol group than in the placebo group at the end of the study. CONCLUSIONS: Low 25-(OH)D status may be related to the elevation in albuminuria and UAGT, and calcitriol may have a beneficial effect on albuminuria through the inhibition of intrarenal RAS in RTRs.

Evaluation of oxidative and nitrosative stress in hemodialysis patients.

AIM: Oxidative/nitrosative stress has long been demonstrated in hemodialysis patients. It is associated with numerous complications such as atherosclerosis and related cardiovascular disturbances. However, the factors influencing oxidative/nitrosative status have not been characterized extensively in these patients. Therefore, the present study was designed to investigate the alteration of oxidative/nitrosative stress parameters and total antioxidant status. METHODS: Forty-one hemodialysis patients and 41 healthy subjects were enrolled in the present study. Serum myeloperoxidase, nitrotyrosine and total antioxidant capacity were determined. RESULTS: Serum myeloperoxidase and nitrotyrosine were significantly higher in the haemodialysis patients compared to the healthy subjects (P<0.05) while total antioxidant capacity was lower (P<0.01). CONCLUSION: According to the results of this study, oxidative and nitrosative stress is increased in haemodialysis patients, therefore these alterations should be considered in the treatment of these patients.

Impaired fibrinolytic and blunted nitric oxide response to phlebotomy in cigarette smoking healthy blood donors.

This study was designed to investigate the effects of smoking on endothelial function in 88 healthy blood donors: 48 smokers and 40 non-smokers. Two markers of endothelial dysfunction, plasminogen activator inhibitor-1 (PAI-1) and nitric oxide (NO) levels, were measured at baseline and after phlebotomy. It has been proposed that phlebotomy acutely activates the renin-angiotensin-aldosterone system, thereby activating endothelial activity and increasing PAI-1 and NO expression. At baseline there were no significant differences between smokers and non-smokers in terms of PAI-1 expression and NO levels. After phlebotomy, both PAI-1 and NO levels were significantly increased in both groups. The increase in PAI-1 was more pronounced in smokers and the increase in NO was more pronounced in non-smokers. These findings suggest that smoking causes endothelial dysfunction, even in healthy smokers, which may remain silent until a clinically evident disorder develops.

Foreign body aspiration: clinical utility of flexible bronchoscopy.

Foreign body aspiration is a worldwide health problem which often results in life threatening complications. More than two thirds of foreign body aspirations occur among children younger than 3 years. Organic materials such as nuts, seeds, and bones are most commonly aspirated. There is a wide range of clinical presentation, and often there is not a reliable witness to supply the clinical history, especially in children. Maintaining a high index of suspicion is therefore necessary for the diagnosis. None of the imaging methods employed in such cases are diagnostic, and bronchoscopy is frequently necessary for the diagnosis as well as the treatment. In adults, removal of the foreign body can be attempted during diagnostic examination with a fibreoptic bronchoscope under local anaesthesia, which may help to avoid any further invasive procedures with more complications. When diagnosis is delayed, complications of a retained foreign body such as unresolving pneumonia, lung abscess, recurrent haemoptysis, and bronchiectasis may necessitate a surgical resection. However, some of the late complications may resolve completely after the retrieval of the foreign body, therefore, a preoperative flexible bronchoscopy should always be considered in suitable cases.

Acute effect of haemodialysis on serum markers of myocardial damage.

Cardiac markers are more likely to be elevated in dialysis patients than in patients with renal failure not on dialysis. In this study, 31 patients (20 males, 11 females) undergoing chronic haemodialysis were enrolled. The effect of haemodialysis on cardiac troponin T (cTnT), I (cTnI), creatine kinase MB (CKMB) mass, CKMB activity and myoglobin assays was assessed by comparing pre- and post-haemodialysis determinations. After correcting for haemoconcentration, significant differences were observed (mean +/- SEM, pre- vs post-dialysis) for myoglobin (178.9 +/- 19.3 vs 225.0 +/- 28.4 ng/ml; p=0.006) for cTnT (0.111 +/- 0.028 vs 0.148 +/- 0.037 ng/ml; p=0.004), for CKMB mass (2.75 +/- 0.37 vs 2.59 +/- 0.37 ng/ml; p=0.000) and CKMB activity (14.8 +/- 0.9 vs 13.1 +/- 0.9 U/l; p=0.000) assays. Our study questions the reliability of cardiac markers in dialysis patients and suggests that the clinical threshold value and diagnostic efficiency of each assay needs to be validated. Although these differences exceeded clinical threshold values in only a few patients, serum markers of myocardial damage in dialysis patients should be interpreted with caution.

Bone mineral density in haemodialysis patients: A comparative study of dual-energy X-ray absorptiometry and quantitative ultrasound.

BACKGROUND: Quantitative ultrasound (QUS) of bone is a relatively new technique that appears to assess 'bone quality' in addition to bone mineral density. The purpose of this study was to evaluate the diagnostic potential of QUS of calcaneum and to correlate it with dual energy X-ray absorptiometry (DEXA) in chronic haemodialysis patients. METHODS: Broad-band ultrasound attenuation (BUA; dB/MHz) and speed of sound (SOS; m/s) of calcaneum and DEXA (g/cm(2)) measurements of the lumbar spine and hip were made in 39 patients. The indices obtained by either method were compared with age-and sex-matched controls. Calcaneal measurements were correlated to DEXA and relevant clinical and biochemical data of patients. RESULTS: BUA and SOS values were markedly reduced in dialysis patients compared to controls (59.1+/-13.8 vs 73.0+/-16.2 dB/MHz, P:<0.001 and 1533+/-28 vs 1560+/-29 m/s, P:=0.014 respectively). There was a moderate, but significant association between calcaneal parameters and DEXA (r=0.32-0.53, P:<0.05). Both BUA and SOS scores were inversely correlated with age (r=-0.69, P:<0.001) and duration of menopause (r=-0.74, P:<0.01). Additionally, BUA values showed a moderate negative association with serum intact parathyroid values (r=-0.38, P:=0.018). CONCLUSION: Chronic haemodialysis patients have reduced calcaneal BUA and SOS scores. QUS of the calcaneum is an easy-to-apply and radiation-free technique. It could be a useful substitute for assessment of bone density in such patients. However, further studies in large patient groups and comparisons with plasma markers of bone turnover and bone biopsy findings are needed to assess its potential place in the management of renal osteodystrophy.

Tc-99m DTPA acetylsalicylic acid (aspirin) renography in the detection of renovascular hypertension.

PURPOSE: Prostaglandins play important roles in renal physiology and in the development of renovascular hypertension. In a recent study, inhibition of renal prostaglandin synthesis was found to be useful for detecting renovascular hypertension using renal scintigraphy. In the current study, the authors evaluated the role of aspirin (an inhibitor of prostaglandin synthesis) and compared it with Tc-99m DTPA captopril renal scintigraphy (CS). MATERIALS AND METHODS: Twenty-five patients were examined with Tc-99m DTPA in a three-step manner: a baseline study, CS, and aspirin scintigraphy (AS). Each scintigraphic study was interpreted visually and according to the renogram curve patterns. Semiquantitative parameters (Tmax, renal indices [%], 20-minute/max count ratio, glomerular filtration rate) were also calculated. Plasma renin activity was determined for each study. The blood pressures of all patients were measured during AS. All patients had a contrast-enhanced angiogram that was used as the reference test. RESULTS: Three groups of patients were observed based on the scintigraphic and angiographic results. In each group, no difference was observed in blood pressure after aspirin administration. In group 1, seven patients had normal angiographic and scintigraphic results. In group 2, eight patients had angiographically confirmed renal artery stenosis (RAS). In 6 patients (mean, 47% RAS), both AS and CS were negative for RVH. In the remaining two patients with RAS (mean, 83% stenosis), the kidneys were atrophic on the stenotic side, and thus the kidneys did not respond to the interventions. No difference was observed in plasma renin activity in groups 1 and 2. Group 3 included 10 patients who had angiographically confirmed RAS (mean, 86%). In 9 patients, both CS and AS were positive for RVH. In the remaining one patient, scintigraphic results were falsely negative. Statistical analyses performed for semiquantitative parameters did not reveal any significant difference in this group, although there was a tendency toward prolonged Tmax values after captopril and aspirin administration. In four cases, unexpected elevation of plasma renin activity was observed in group 3. CONCLUSIONS: These data indicate that AS with Tc-99m DTPA is an alternative for CS. It has the advantage of having no effect on blood pressure and does not require that angiotensin-converting enzyme inhibitors be discontinued. Although in this study 9 of 10 patients had correct diagnoses of RAS, further studies, especially using tubular agents with the calculation of parenchymal transit time, might provide valuable information in this patient group. An ongoing study is being performed in the authors' institute.

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.

Determinants of soluble CD23 antigen levels in hemodialysis patients: effect of 1.25 dihydroxyvitamin D3 and recombinant human erythropoietin treatment.

BACKGROUND: The immunodeficiency of end-stage renal disease (ESRD) paradoxically coexists with T cell and monocyte activation. In spite of well known defective antibody responses in ESRD, the functional status of B cells in the immune system dysregulation of uremia is still controversial. Soluble CD23 (sCD23) antigen is a recently identified B cell activation marker and is also involved in T cell activation process. Effects of parathyroid hormone (PTH), red blood cells and ferritin on T and B cell functions have been shown both in vivo and in vitro. PATIENTS AND METHODS: In this study, serum levels of sCD23 in hemodialysis patients were determined to evaluate the functional status of B cells and possible linkages between this cytokine and PTH levels, ferritin levels, red blood cell counts were investigated. RESULTS: Serum sCD23 levels were significantly elevated in hemodialysis patients relative to healthy controls (12.5+/-8.4 micro/l vs. 2.4+/-1.1 micro/l, p<0.001). Serum sCD23 levels were negatively correlated with red blood cell count (r = -0.61, p = 0.009) and serum PTH levels (r = -0.62, p = 0.008), while positively correlated with serum ferritin levels (r = 0.63, p = 0.007) in hemodialysis patients. We also investigated the immunumodulator effects of 1.25 dihydroxyvitamin D3 (1.25OHD3) and recombinant human erythropoietin (rHu-Epo) treatment in hemodialysis patients. 1.25OHD3 treatment for eight weeks did not change serum sCD23 levels in hemodialysis patients (n = 8). On the other side, rHu-Epo administration for 16 weeks led to a decrease in serum sCD23 levels (17.7+/-8.6 microg/l vs. 9.8+/-3.5 microg/l, p = 0.007) in these patients (n = 9). CONCLUSION: These results suggests that similar to T cells, B cells are activated in uremia and the degree of this activation is correlated with red blood cell count, serum parathyroid hormone levels and iron status of the hemodialysis patients. Moreover, B cell activation could be altered by recombinant human erythropoietin therapy in hemodialysis patients.

Serum thrombopoietin levels in haemodialysis patients: involvement of arteriovenous fistula.

BACKGROUND: Thrombopoietin (Tpo) is a recently cloned growth factor which plays a critical role in the regulation of thrombopoiesis. Tpo has also been shown to stimulate in vitro and in vivo erythroid cell growth. Although Tpo transcripts were detected in hepatocytes, proximal tubules and endothelium, mechanisms regulating the level of circulating Tpo have not been fully delineated. Changes in the vessel wall and blood flow in arteriovenous fistula (AVF) might alter Tpo activity. METHODS: Serum thrombopoietin levels and serum erythropoietin levels in samples concurrently obtained from venous returns of AVF and contralateral peripheral veins in 31 haemodialysis patients were determined and compared with 12 healthy controls. Levels were also compared between 14 haemodialysis patients (group I) treated with recombinant human erythropoietin (rHu-Epo) and 17 haemodialysis patients (group II) not requiring rHu-Epo. RESULTS: Serum Tpo levels (44.8 +/- 23.9 pg/ml, vs 129.9 +/- 113.6 pg/ml, P<0.05) and platelet counts (194 +/- 55, 10(6)/ml vs 273 +/- 94. 10(6)/ml, P<0.05) of haemodialysis patients were lower than healthy controls. Serum Tpo levels were inversely correlated with platelet counts in the control group (R=-0.61, P<0.05), but not in haemodialysis patients. Tpo concentrations of AVF samples were lower than peripheral venous samples (31.6 +/- 17.7 pg/ml vs 44.8 +/- 23.9 pg/ml, P=0.001). No significant difference was present between the serum Tpo concentrations of haemodialysis patients in group I and group II. Serum Tpo levels were not correlated with haemoglobin levels or serum erythropoietin levels in haemodialysis patients. CONCLUSION: Decreased serum Tpo levels despite low platelet counts in haemodialysis patients suggest that the proposed feedback mechanism of platelet uptake of Tpo is not fully operative in these patients. Moreover, AVF might affect the local production and/or catabolism of this growth factor.

Cyclical acute renal failure due to bilateral ureteral endometriosis.

Endometriosis is a common disease but ureteral involvement is relatively rare. Ureteric endometriosis is mostly unilateral. Endometriotic ureteral obstruction is a serious event commonly diagnosed late and therefore associated with a major risk of hydronephrotic renal atrophy. We present the cyclical acute renal failure associated with menstruation in a patient who developed severe bilateral ureteral obstruction due to endometriosis. Physicians should be aware of this uncommon but serious manifestation of endometriosis, especially if the clinical presentation is cyclical acute renal dysfunction in a premenopausal woman.

Acute lymphoblastic leukaemia presenting with arthritis in an adult patient.

The earliest manifestations of leukaemia often include rheumatic signs and symptoms. Arthritis is a well recognised complication of leukaemia in children, but acute and chronic leukaemia may also cause arthritis in adults. Leukaemic arthritis may occur at any time during the course of leukaemia and may be the presenting manifestation. It should therefore be considered in the differential diagnosis of both childhood and adult rheumatic disease. We present an adult patient presenting with arthritis due to acute leukaemia.

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.