Urinary angiotensinogen level is increased in renal transplant recipients with masked hypertension and is correlated with left ventricular mass index and albuminuria in these patients.

Activation of the local renin-angiotensin system (RAS) is an independent risk factor for the development of proteinuria and left ventricular hypertrophy (LVH) more commonly seen in masked hypertensives. It has been reported that urinary angiotensinogen (UAGT) level provides a specific index of the intrarenal RAS status. The aim of this study was to evaluate the association between UAGT and left ventricular mass index (LVMI) and urinary albumin-creatinine ratio (UACR) in renal transplant recipients (RTRs) with masked hypertension (HT). A total of 116 non-diabetic-treated hypertensive RTRs were included in this study. The patients were divided into two groups: masked hypertensives and controlled hypertensives. Forty-two (36.2%) of RTRs had masked HT. Mean UACR and LVMI levels were higher in RTRs with masked HT than in RTRs with controlled HT (P < 0.001). UAGT level was also higher in masked hypertensives compared to controlled hypertensives (P < 0.001). Multivariable regression analysis showed that UAGT was positively correlated with UACR (ß = 0.024, P = 0.001) and LVMI (ß = 0.082, P = 0.001) in masked hypertensives. Consequently, masked HT was considerably frequent (36.2%) in treated hypertensive RTRs and high UAGT levels accompanied by high albuminuria and LVMI levels were seen in these patients. Overproduction of the UAGT may play a pivotal role in the development of LVH and proteinuria in masked hypertensives.

Urinary angiotensinogen level is correlated with blood pressure level and proteinuria in patients with masked hypertension.

Urinary angiotensinogen (UAGT) level is an index of the intrarenal-renin angiotensin system status and is significantly correlated with blood pressure (BP) and proteinuria in patients with hypertension (HT). We aimed to investigate the possible relationship between UAGT levels and albuminuria in masked hypertensives. A total of 96 nondiabetic treated hypertensive patients were included in this study. The patients were divided into two groups: masked hypertensives (office BP <140/90 mmHg and ambulatory BP ≥130/80 mmHg) and controlled hypertensives (office BP <140/90 mmHg and ambulatory BP <130/80). The mean UAGT/UCre level and urinary albumin-creatinine ratio (UACR) of masked hypertensives were higher than those of controlled hypertensives (7.76 µg/g vs 4.02 µg/g, p < 0.001 and 174.21 mg/g vs 77.74 mg/g, p < 0.001, respectively). A significant positive correlation was found between UAGT/UCre levels and ambulatory systolic BP and diastolic BP levels in patients with masked HT, but this was not found with office SBP or DBP levels. Importantly, UAGT/UCre levels showed a significant positive correlation with UACR in both groups, but correlation of the UAGT levels with UACR was more pronounced in masked hypertensives (r = 0.854, p < 0.001 vsr = 0.512, p < 0.01). As a result, UAGT level was increased in patients with masked HT, which was associated with an elevation in albuminuria. Overproduction of the UAGT may play a pivotal role in development of proteinuria.

Vitamin D receptor activation with calcitriol for reducing urinary angiotensinogen in patients with type 2 diabetic chronic kidney disease.

BACKGROUND: Recently, it has been reported that urinary angiotensinogen levels is a specific index of the intrarenal renin-angiotensin-aldosterone system (RAAS) status and it is significantly correlated with urinary albumin:creatinine (Cr) ratio in hypertensive patients. The aim of the present study was to assess the effect of activation of the Vitamin D receptor with calcitriol on albuminuria and urinary angiotensinogen as a novel biomarker of the intra-renal RAAS status in patients with diabetic nephropathy (DN). METHODS: Ninety-eight patients with type 2 diabetes and albuminuria who were treated with RAAS inhibitors (angiotensin-converting enzyme inhibitor (ACE-i) or angiotensin receptor blocker (ARB)) have participated in this study. Patients were randomized to receive either placebo (n = 50) or 0.25 µg/day calcitriol (n = 48). We have examined urinary albumin:Cr ratio and urinary angiotensinogen:Cr ratio before and 24 weeks later after treatment in both group. RESULTS: The mean urinary albumin:Cr ratio and urinary angiotensinogen:Cr ratio were significantly higher in patients with DN than in normal controls (p < 0.001). Urinary angiotensinogen:Cr ratio was significantly, positively correlated with urinary albumin:Cr ratio in both groups (in the placebo group; p = 0.01, r = 0.4236, in calcitriol group; p = 0.01, r = 0.4564). CONCLUSION: These data indicated that administration of Vitamin D receptor activator in combination with RAAS inhibitors had an additional benefit in lowering albuminuria in patients with DN. More pronounced reduction of urinary albumin:Cr ratio that was positively correlated with angiotensinogen:Cr ratio in calcitriol group suggested that Vitamin D receptor activation might blunt albuminuria by reducing urinary angiotensinogen levels reflecting intra-renal RAAS status.

Association between urinary angiotensinogen excretion rates and left ventricular mass index and carotid intima-media thickness in hypertensive kidney transplant recipients.

OBJECTIVES: The renin-angiotensin system (RAS) is thought to regulate blood pressure and to be an independent risk factor for the development of left ventricular hypertrophy (LVH) and carotid intima-media thickness (CIMT). Locally produced RAS in most tissues has been recently described. It has been reported that urinary angiotensinogen levels provide a specific index of the intrarenal RAS status and is significantly correlated with blood pressure and proteinuria. The aim of this study was to evaluate the relationship of local intrarenal RAS with LVH and CIMT in hypertensive renal transplant recipients (RTRs). RESULTS: A total of 96 non-diabetic RTRs (50 hypertensive patients, 46 normotensive patients) were included in this study. Urinary angiotensinogen (UAGT)/urinary creatinine (Ucre) was significantly higher in hypertensive patients compared with normotensive patients (p < 0.01). Left ventricular mass (LVM)I and CIMT were significantly higher in hypertensive patients compared with the normotensive patients (p < 0.01). Importantly, a significant positive correlation was found between UAGT/Ucre levels and LVMI (r = 0.724, p = 0.012) and also CIMT (r = 0.452, p = 0.02) in hypertensive RTRs. CONCLUSIONS: These data indicate that UAGT is increased in hypertensive RTRs, and local RAS may play an important role in the development of cardiovascular abnormalities in hypertensive renal transplant recipients.

Effects of Induction Therapy on Graft Functions in Terms of Immunologic Risk.

BACKGROUND: Advances in immunosuppressive therapies and surgical techniques have led to a significant reduction in the incidence of rejection within 1 year after kidney transplantation. Immunologic risk is an important factor affecting graft functions and guiding the clinician in the selection of induction therapy. The aim of this study was to investigate graft functions based on serum creatinine levels, Chronic Kidney Disease Epidemiology Collaboration (CKD- EPI) and proteinuria levels, frequency of leukopenia, cytomegalovirus (CMV) and BK virus polymerase chain reaction (PCR) positivity in patients with low and high immunologic risk. MATERIAL AND METHODS: This retrospective study included 80 renal recipients. Recipients were divided into 2 groups: patients at low immunologic risk who received basiliximab only and those with high immunologic risk who received low-dose (1.5 mg/kg for 3 days) antithymocyte globulin and basiliximab. RESULTS: No significant differences were observed between the 2 risk groups in terms of first, third, sixth, and 12th-month creatinine levels, CKD-EPI, proteinuria levels, leukopenia frequency, and CMV and BK virus PCR positivity. CONCLUSION: One-year graft survivals did not differ significantly between these 2 treatment modalities. The combined use of low-dose antithymocyte globulin and basiliximab in the induction treatment of patients with high immunologic risk seems promising in terms of graft survival, leukopenia frequency, and CMV and BK virus PCR positivity.

Effects of lisinopril, irbesartan, and amlodipine on the thrombogenic variables in the early and late stages of the treatment in hypertensive patients.

Regulation of the fibrinolytic balance between plasminogen activators and inhibitors is modulated by the renin-angiotensin system (RAS). Impaired fibrinolytic function, characterized by increased plasminogen activator inhibitor type 1 (PAI-1) levels and decreased tissue plasminogen activator (t-PA) activity, has been found in patients with hypertension and may account in part for the increased risk of atherosclerosis and its clinical complications in these patients. In this regard, data from the literature indicate that different antihypertensive drugs may vary in their influence on fibrinolysis. Angiotensin-converting enzyme (ACE) inhibitors (ACE-I) have generally been shown to improve the fibrinolytic balance by reducing plasma PAI-1 levels. Calcium-channel blockers (CCB) have been reported to increase t-PA activity, and angiotensin receptor blockers (ARB) seem to be neutral in their effect. In the light of these data, this study aimed to compare the effects of ACE-I, ARB, and CCB on the fibrinolytic system in the early and late stages of the treatment in hypertensive patients. These data that the beneficial effect of RAS inhibition on fibrinolysis related to decrease in Ang II during early period of treatment. Amlodipine may also improve thrombogenic risk related to lowering the effect on increased platelet activation reflected by p-selectin. The greater improvement in the early and late stages of the fibrinolytic balance because of the combined action of RAS inhibition and Ca antagonism represents a further indication to the use of combinations of RAS inhibition (ACE-I or ARB) and CCB in the treatment of hypertension.

Effect of allopurinol drug use on GFR and proteinuria in patients with renal transplant recipients (ADOPTR study).

BACKGROUND: Hyperuricemia has been associated with the development of hypertension, cardiovascular, and renal disease. However, there is no data about the effect of lowering uric acid level on renal functions and proteinuria in renal transplant recipients. This study aimed to investigate the effect of allopurinol treatment on renal functions in renal transplant recipients (RTR). METHODS: A total of 245 patients with renal transplantation were included in this randomized, placebo-controlled study. Patients were randomized to receive either placebo (121 patients) or 300 mg/day allopurinol (124 patients). We have examined uric acid, urinary protein creatinin ratio, MDRD (the modification of diet in renal diseases) and CRP (C-reactive protein) before and 24 weeks after treatment in both group. RESULTS: In the allopurinol group, the mean serum uric acid levels, eGFR (estimated glomerular filtration rate), and creatinine urinary albumin creatinin ratio (UACR) significantly improved (p < 0.001). Also uric acid level was positively correlated with the UACR (r = 0,645 p < 0.001) and negatively correlated with MDRD (r = -0,387 p < 0.05) in allopurinol treatment group. A statistically significant increase in CRP level was observed (p < 0,05) in plasebo group. Multivariate regression analysis showed that uric acid was positively correlated with UACR (r = 0,473, ß = 0.021, p = 0.002) and negatively correlated with MDRD (r = -0554 ß = 0.016, P = 0.001) in allopurinol treatment RTR. CONCLUSION: Urate, a salt of uric acid, is lowered by allopurinol treatment resulting in improved eGFR and decreased proteinuria, when compared to the placebo group. Therefore, we suggest that allopurinol therapy should be part of the management of kidney transplant patients with normal kidney function. Long-term follow-up studies will be useful in revealing the effect of uric acid management on kidney functions and proteinuria.

Effect of combined angiotensin-converting enzyme and aldosterone inhibition on plasma plasminogen activator inhibitor type 1 levels in chronic hypertensive patients.

AIM: A possible link between the renin-angiotensin-aldosterone system (RAAS) and fibrinolysis has recently been suggested. Systemic infusion of angiotensin II results in an increase in plasminogen activator inhibitor type 1 (PAI-1) levels and angiotensin-converting enzyme inhibitors (ACEI) have been shown to decrease PAI-1 levels. Moreover, recent data indicated that plasma aldosterone levels were positively correlated with plasma PAI-1 levels. This study was designed to compare the effects of an ACEI with an ACEI in combination with an aldosterone antagonist on PAI-1 levels in chronic hypertensive patients. METHODS: Patients were randomized into two groups and were treated with either low salt diet plus fosinopril (group 1, n = 43) or low salt diet plus fosinopril plus spironolactone (group 2, n = 42). Plasma PAI-1, tissue plasminogen activator (tPA) and plasma renin activity (PRA) levels were measured before and after 24 week treatment in both groups. RESULTS: The mean basal PRA levels were similar in both groups. After antihypertensive therapy, the mean PRA increased significantly in both groups (P < 0.005). The mean plasma PAI-1 levels were reduced in both treatment groups (P < 0.005). However, the reduction in group 2 was more pronounced (P < 0.05). Although after the treatment mean plasma levels of PAI-1 significantly reduced in both groups, the reduction of PAI-1 levels was more pronounced in group 2. CONCLUSION: Although the plasma levels of PAI-1 significantly reduced after treatment in both groups, the reduction of PAI-1 levels was more pronounced in group 2. These data indicated that administration of aldosterone antagonists in combination with ACEI had additional benefit on fibrinolysis in chronic hypertensive patients.

Plasma plasminogen activator inhibitor 1 (PAI-1) and P-selectin levels in urgent hypertension: effect of single dose captopril and nifedipine on fibrinolytic activity.

In this study, we primarily aimed to identify the acute effects of hypertension on fibrinolytic function in previously untreated urgent hypertensive patients and to evaluate the influence of two commonly used, short-acting, anti-hypertensive agents, captopril and nifedipine, in these patients. Patient groups were selected homogeneously, i.e., only previously untreated patients amidst an urgent hypertensive episode and having no co-morbid disease were included-and randomly assigned to receive either captopril or nifedipine for immediate management. These two treatment groups were matched for age, gender, and mean arterial blood pressure. Study results demonstrated that lowering blood pressure with either agent improved fibrinolytic function; however, in those patients given captopril, this beneficial effect was more prominent, providing evidence supporting the preferential use of short-acting, angiotensin-converting enzyme (ACE) inhibitors in this setting.

An unusual manifestation of brucellosis infection: acute renal failure.

Brucellosis is a disease of multisystem organ involvement and resembles many other diseases. Rare involvements of the disease include musculoskeletal, gastrointestinal, cardiovascular, and central nervous systems, while renal involvement is exceedingly rare. Herein, we present a case of acute renal failure (ARF) due to brucellosis infection manifesting with progressively elevated urea and creatinine levels. To our knowledge, this is the first case report to reveal an association between brucellosis infection and (ARF) in the literature. We wish to present this unusual manifestation of brucellosis infection in the hope that it will be a nice contribution to the pathogenesis of the disease and to the literature.

Function of dynamically stimulated endothelium and renin-angiotensin-aldosterone system in normotensive subjects with a family history of hypertension.

AIM: Genetic influences on the acute stimulation of the renin-angiotensin-aldosterone system (RAAS) and on endothelial activation were studied by examining healthy blood donors with and without hypertensive parents. METHODS: Healthy blood donors were assigned to two groups, according to the presence or absence of a parental history of hypertension. Plasma levels of renin, nitric oxide (NO) and plasminogen activator inhibitor 1 (PAI-1) were studied before and after acute alterations in renal perfusion induced by phlebotomy, and the two groups compared. During phlebotomy, 400-500 mL of blood was extracted from each subject, with that volume varying relative to each subject's body surface area (m(2)). RESULTS: No statistically significant inter-group differences were observed between the baseline mean levels of plasma renin, NO or PAI-1. After phlebotomy, significant increases were detected in mean plasma renin activity (PRA) and NO levels and in PAI-1 activity (P < 0.001). However, the increases in mean PRA (P < 0.05) level and PAI-1 activity (P < 0.05) were more pronounced in those with hypertensive parents than those without; conversely, the increase in NO levels was more pronounced in the latter group. No statistically or clinically significant difference was found between the mean body mass indices of these two groups. Only two subjects were overweight, and none were obese; the remainder had weights that were normal. We found no significant correlation between body mass index and either NO or PAI-1 level. CONCLUSION: Post-phlebotomy, PRA and PAI-1 responses were more dramatic, but the NO response less in normotensive subjects having a parental history of hypertension, suggesting that these changes may represent familial, possibly genetic influences before overt hypertension occurs.

A dynamic comparative study concerning the effects of angiotensin-converting enzyme inhibitors and aldosterone receptor blockers on the fibrinolytic system.

The renin-angiotensin-aldosterone system (RAAS) plays a central role in fibrinolysis. Activation of the RAAS stimulates the expression of plasminogen activator inhibitor-1 (PAI-1), which can be directly implicated in the pathophysiology of thromboembolic events. Our primary aims were to measure (1) the effect of acute RAAS activation on plasma levels of PAI-1, and (2) the inhibitory effect of an angiotensin-converting enzyme (ACE) inhibitor alone, versus a combination of an ACE inhibitor and aldosterone blockade on the increase in PAI-1 usually observed. In the current prospective in vivo study, RAAS was activated by means of phlebotomy, an effective, physiologic means of RAAS activation. Seventeen voluntary prehypertensive, but otherwise healthy, blood donors were included in this study. Renin and PAI-1 levels were measured before and after initial phlebotomy. At the time of the second phlebotomy, 12 of 17 donors randomly were assigned to receive enalapril (5 mg) or a combination of enalapril (5 mg) plus spironolactone (25 mg), beginning 3 days before phlebotomy, and 5 were assigned to be controls, receiving no medications. Plasma renin and PAI levels were significantly increased following initial phlebotomy. At the time of the second phlebotomy, plasma PAI-1 activity was reduced significantly, as compared with the initial phlebotomy, but it did not return to baseline levels. The observed mean reduction in PAI-1 level was greater among the subjects who received both ACE and aldosterone inhibition. Enalapril and the combination of enalapril plus spironolactone efficiently reduce PAI-1 levels, but the reductions are more pronounced with the combined regimen. However, neither treatment appears sufficient to return PAI-1 activity to baseline levels.

Systemic lupus erythematosus complicated by dilated cardiomyopathy and severe heart failure.

Systemic lupus erythematosus (SLE) is the prototype autoimmune disorder, one that is known for its many, diverse modes of presentation. In this paper, we present a further unusual presentation of SLE, that of acute onset, severe heart failure secondary to dilated cardiomyopathy. Only a few similar cases have been reported in the literature.

Takayasu arteritis: association with focal segmental glomerulosclerosis.

We herein report on a 29-year-old woman who presented with edema and proteinuria. In light of her blood pressure differences and, finally, with the angiographic findings, Takayasu arteritis (TA) was the diagnosis. Renal biopsy showed focal segmental glomerulosclerosis (FSGS) and other possible etiologic alternatives were excluded. This was a very rare association and we could not find any other cases reported on TA accompanied with FSGS before. A poor treatment response was observed at the end of a 1-year therapy.

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.

Superior vena cava thrombosis in chronic lead exposure--a case report.

Thrombosis is a rare cause of superior vena cava syndrome (SVCS). A 43-year-old male patient with SVCS due to thrombosis underwent investigation for the etiology of thrombus formation. He had been hospitalized several times because of lead intoxication in the past. Lead has a known thrombogenetic effect experimentally. This patient with superior vena cava thrombosis had thrombophilia that was probably due to lead intoxication. The etiologies of venous thrombosis and thrombogenetic effect of chronic lead exposure are discussed.

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-alpha) 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-alpha levels were measured before, 24 hours and 7 days after angiography. RESULTS: SCre and 24 hour urinary GST-alpha 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-alpha excretion rates. Pretreatment with a long acting calcium antagonist amlodipine has no effect on the course of enzyme excretion and alteration observed in SCre.

Bilateral renal mass-renal disorder: tuberculosis.

A 30-year-old woman has presented complaining of weakness and fatigue to her primary care physician. The renal sonography is a routine step in the evaluation of new onset renal failure. When the renal masses have been discovered by sonography in this setting, the functional imaging may be critical. We reported a case about bilateral renal masses in a young female patient with tuberculosis and renal insufficiency. Magnetic resonance (MR) has revealed the bilateral renal masses in patient, and this patient has been referred to our hospital for further management. The patient's past medical and surgical history was unremarkable.

Successful treatment of a rare complication of Henoch-Schönlein purpura in advanced age: pulmonary hemorrhage.

Henoch-Schönlein purpura (HSP) is a form of systemic vasculitis involving both arterioles and capillaries. HSP frequently is seen in children between the ages of 2 and 11 years, though adults with this disease are occasionally encountered. Although it primarily is a disease of early childhood, it can occur at any age. The clinical manifestations include a classic tetrad: rash, arthralgias, abdominal pain and renal disease. However, it may affect almost any other bodily tissue, such as myocardium, lungs, ureter and nervous system. Pulmonary hemorrhage is a rare complication of HSP, which largely has been observed in adolescents and adults. Pulmonary hemorrhage in HSP is associated with significant morbidity and mortality. We present the successful treatment of a 78-year-old woman with HSP complicated by pulmonary hemorrhage.