The time course of gastric methotrexate intolerance in patients with rheumatoid arthritis and psoriatic arthritis.

OBJECTIVES: This study aimed to evaluate the incidence and the time course of methotrexate (MTX)-associated gastric intolerance in patients with rheumatoid arthritis and psoriatic arthritis. METHODS: Four hundred twenty subjects undergoing MTX treatment for rheumatoid arthritis (n = 346) and psoriatic arthritis (n = 74) were retrospectively assessed. The incidence and time course of gastric MTX intolerance resulting in treatment discontinuation were investigated. In addition, the relations between gastric intolerance and patient characteristics, including gender, age, diagnosis, and rheumatoid factor (RF) positivity, were examined. RESULTS: Overall, oral MTX discontinuation rate due to gastric intolerance was 28.6 %. The time to discontinuation for oral MTX was 8.1 ± 11.5 months on average, with more than half of the discontinuations occurring within the first three months of treatment. Discontinuation was not associated with gender, age, diagnosis, or RF positivity. More than half of the patients that switched to a parenteral treatment regimen (52.6 %, 20/38) could tolerate the agent. CONCLUSIONS: Gastric MTX intolerance usually develops within the first year of treatment and presents a major obstacle to long-term treatment retention in patients with rheumatologic disease. However, parenteral MTX appears to be a good alternative for patients intolerant of oral MTX.

Tumor necrosis factor-alpha antagonist therapy-induced psoriasis in Turkey: analysis of 514 patients.

OBJECTIVES: New adverse events are being reported with the increased use of anti-tumor necrosis factor (TNF) α therapy. We studied cases of anti-TNFα-induced psoriasis observed in our pool of 514 patients receiving anti-TNFα treatment in Turkey. METHODS: Three rheumatoid arthritis patients and 3 ankylosing spondylitis patients with anti-TNFα-induced psoriasis were included in the study. All patients were examined by a dermatologist, and 3 patients underwent skin biopsy. RESULTS: None of the 6 patients had preexisting psoriasis or a familial history of psoriasis. The earliest and latest occurrences of psoriatic lesions were at the 6th week and 44th month of anti-TNFα therapy, respectively. Psoriasis was severe and refractory in two patients (requiring systemic treatment), while it presented as mild in four patients. Anti-TNFα therapy was totally withdrawn in case 1. In case 2, the treatment was halted for 3 months then switched to another TNFα blocker, and case 3 was switched to another anti-TNFα treatment. The treatment was sustained in the other 3 patients (cases 4, 5, and 6). CONCLUSIONS: TNFα blockers are very effective agents in the treatment of psoriasis, but it is interesting that the same molecules can, paradoxically, induce psoriasis. The occurrence of anti-TNFα-induced psoriasis in six out of 514 patients suggests that the incidence of this adverse reaction is, in fact, as not low as presumed in the literature. In some cases, a severe course of psoriasis may limit the use of these agents.

The relationship between lymphocyte subsets, nutritional status and tuberculin reactivity in continuous ambulatory peritoneal dialysis and hemodialysis patients.

AIM: Skin test anergy is common in patients with uremia and during maintenance hemodialysis treatment. However, up to date only one study concerning skin test in peritoneal dialysis patients has focused on the issue. Our cross-sectional controlled study was conducted to analyze the correlation of purified protein derivative (PPD) test response with demographical features, nutritional parameters and the distribution of peripheral blood lymphocyte subsets in peritoneal dialysis and hemodialysis patients PATIENTS AND METHODS: Stable 30 hemodialysis (HD) patients (16 men, 14 women) and 30 continuous ambulatory peritoneal dialysis (PD) patients (17 men, 13 women) were included. Thirty healthy cases (15 men, 15 women) with a mean age of 32.4 ± 9.4 constituted the control group. RESULTS: In the HD group, 14 patients (46.6%) were PPD positive, and in the PD group 16 patients (53.3%) were PPD positive. In the PPD-positive HD patients 64.2% (9/14), and in the PPD-positive PD patients 62.4% (10/16) had an induration of 10 mm or greater. In the control group, 21 of 30 patients (70%) were PPD positive. Comparison of both HD and PD groups with the control group showed significant differences in PPD reactivity (p < 0.01). Albumin levels were significantly high in the control groups (p < 0.01), and cholesterol levels were significantly high in the PD and the control groups (p < 0.05). Transferrin levels were significantly high in the PD (p < 0.01). The lymphocyte counts were significantly high in the control group compared to the HD patients (p < 0.05). The lymphocyte subset percentages CD19 were high in the control groups (p < 0.05), and CD16/56 was significantly high in the PD groups (p < 0.05). All the parameters were also similar between PPD-positive and -negative same groups. CONCLUSION: The prevalence of PPD positivity was lower in the PD and HD groups. The PPD test responses were not related to the peripheral lymphocyte counts, subsets and malnutrition parameters.

Spontaneous perirenal hematoma with AA amyloidosis in a hemodialysis patient after unilateral nephrectomy.

Secondary amyloidosis presents with a variety of systemic symptoms or signs. Amyloid diseases can be associated with potentially life-threatening hemorrhage. Although bleeding manifestations are common in amyloidosis, renal bleeding is rare and generally due to trauma, cyst and malignancy. For the first time we present a ureamic patient who was diagnosed with AA amyloidosis after unilateral nephrectomy because of spontaneous perirenal hematoma.

Oxidative stress and ferritin levels in haemodialysis patients.

BACKGROUND: Increased oxidative stress (OS) and inflammation are associated with atherosclerotic coronary artery disease in haemodialysis (HD) patients. Ferritin may have other effects in addition to its role in storing intracellular iron. This study was performed to determine any relationships between markers of OS, nutrition and inflammation in HD patients with normal and high ferritin levels. METHODS: Our cohort comprised 34 maintenance dialysis patients on erythropoietin therapy and 22 healthy controls. HD patients were divided into two groups: 17 with normal (<800 ng/ml) and 17 with high (>800 ng/ml) ferritin levels, and we measured lipid profile, albumin, highly sensitive C-reactive protein (hsCRP), anti-oxidant enzymes [whole blood glutathione peroxidase (Gpx), serum superoxide dismutase (SOD), paraoxonase, arylestherase (AE) and total anti-oxidant status (TAOC)], anti-oxidants (vitamin C) and lipid peroxidation products [red blood cell malondialdehyde (RBC MDA)]. RESULTS: Compared with controls, the HD patients had higher serum urea, blood pressure, triglyceride, hsCRP, RBC MDA, SOD and TAOC values and lower albumin, low-density lipoprotein cholesterol, apolipoprotein AI, paraoxonase, AE and whole blood Gpx activities. Serum vitamin C, uric acid, apolipoprotein B, total- and high-density lipoprotein cholesterol, apolipoprotein B MDA, and lymphocyte levels in the HD patients with normal and high ferritin levels were similar. The OS markers of HD patients did not differ, whether or not they received intravenous iron supplementation or had transferrin saturations < 50% or > or = 50%. CONCLUSION: HD patients are in a higher oxidative state, which results in the reduction of total anti-oxidant capacity and also have an increased inflammation status. We could not find a relationship between ferritin level and OS markers in HD patients receiving erythropoietin.

Clinical value of the malnutrition-inflammation-atherosclerosis syndrome for long-term prediction of cardiovascular mortality in patients with end-stage renal disease: a 5-year prospective study.

BACKGROUND/AIM: Mortality resulting from cardiovascular disease in patients with end-stage renal disease (ESRD) is high. In this study we sought to investigate the clinical value of the malnutrition-inflammation-atherosclerosis (MIA) syndrome for long-term prediction of cardiovascular mortality in patients treated with ESRD. METHODS: A total of 42 ESRD patients on hemodialysis were enrolled. Inflammatory markers and nutritional parameters were determined. Carotid atherosclerosis was investigated by ultrasonographically evaluated carotid intima-media thickness (cIMT). Mortality was evaluated at a 5-year follow-up. RESULTS: No correlation was evident between nutritional markers and inflammatory indexes. cIMT was inversely correlated with predialysis serum albumin. In the overall population of 42 patients, 11 (26.2%) died of cardiovascular causes during follow-up. Kaplan-Meier survival curves indicate that cIMT (> or =0.9 mm), C-reactive protein (CRP) (>1 mg/dl), and serum albumin (<3.5 g/dl) predict cardiovascular death in patients with ESRD. CONCLUSIONS: We have demonstrated that cIMT, CRP and serum albumin predict long-term mortality in ERSD patients. Our study suggests that further investigation of the MIA syndrome will provide insights into the susceptibility to CVD in this patient group.

Calcineurin inhibitors and post-transplant weight gain.

AIM: Excessive weight gain that leads to obesity is quite common after kidney transplantation. This is often attributed to immunosuppression. The aim of this retrospective study was to assess the effect of calcineurin inhibitors on post-transplant weight gain. METHODS: A total of 99 patients were studied. The patients were divided into cyclosporine A (CyA) and tacrolimus (Tac) groups and were evaluated for weight changes and risk factors related to weight gain. RESULTS: The weights of patients in both groups significantly increased after the sixth month. The median weight gain at 12 months was 3.5 and 8.0 kg compared with pretransplant dry weight in the Tac and CyA groups, respectively. The increases in the CyA group were significant compared with those of the Tac group. The prevalences of obese and overweight patients in both groups did not differ during a 12-month follow-up. The frequencies of diabetes mellitus, hypertension and dyslipidemia were comparable in both groups. The decrease in systolic blood pressure (BP) of the Tac group was significant compared with the decrease in the CyA group at the 12th month. In the 12-month follow-up period, the increases in triglyceride, total- and low-density lipoprotein-cholesterol values of the CyA group were significantly higher than those of the Tac group. The weight change between 0 and 12 months was negatively correlated with pretransplant body mass index (BMI) and positively with cumulative corticosteroid doses, total-cholesterol and BP changes. CONCLUSION: Only pretransplant BMI, creatinine clearance, CyA usage, being hypertensive and dyslipidemic were independent predictors of weight gain at the 12th month. Our results suggested that the type of immunosuppression may affect post-transplant weight gain.

Acute colchicine intoxication during clarithromycin administration in patients with chronic renal failure.

Colchicine is an effective antiinflammatory medication. It should be used with great caution, however, in patients requiring dialysis. Coadministration of colchicine and macrolides may impair colchicine elimination, resulting in excess drug exposure and toxicity. We report 2 renal failure cases of colchicine intoxication occurring with the administration of clarithromycin.

Comparison of higher dose of losartan treatment with losartan plus carvedilol and losartan plus ramipril in patients with glomerulonephritis and proteinuria.

BACKGROUND: Proteinuria may cause a worsening of accompanying renal disease or even lead to glomerulosclerosis. There is no data about the effect of carvedilol on patients with proteinuric (>0.5 g/day) glomerulonephritis. This study aimed to compare the effects of carvedilol with ramipril and losartan in patients with proteinuric glomerulonephritis. METHODS: Twenty-one glomerulonephritis patients were followed for 12 months. Patients were divided into three groups. All patients were treated with losartan 50 mg once daily for two weeks. After two weeks (baseline), patients were given additional medications: 50 mg losartan, 5 mg ramipril, and 25 mg carvedilol were given additionally to the patients in groups 1, 2, and 3 respectively. RESULTS: Baseline mean proteinuria values of patients in groups 1, 2 and 3 were 1.6 +/- 1.1 g/day, 2.1 +/- 1.3 g/day, and 1.4 +/- 1.2 g/day, respectively. These values decreased to 0.5 +/- 0.7 g/day, 0.6 +/- 0.7 g/day, and 0.9 +/- 0.9 g/day, respectively, at the end of the 12th month. These results were statistically significant only in group 1 (p = 0.04). The rational variation of proteinuria between the first and 12th month of losartan, ramipril, and carvedilol were -61%, -62%, and -27%, respectively. The decreases in blood pressures between baseline and the first, sixth, and twelfth-month measurements were significant in all groups. CONCLUSIONS: Thee results showed that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (AT1ras) provide marked decreases in proteinuria, making their use indisputable in patients with glomerulonephritis. Carvedilol was not found to be as effective as ACEIs and AT1ras in decreasing proteinuria and preserving renal function.

Paraoxonase activity in glomerulonephritic patients.

BACKGROUND: Cardiovascular disease is the most common cause of morbidity and mortality in patients with chronic renal failure. Glomerulonephritic patients have an increased risk for cardiovascular disease, but its etiology is unclear. It is known that an increase in oxidizability of apolipoprotein B-containing lipoproteins has a key role in the initiation of atherosclerosis, and paraoxonase enzyme activity particularly has a preventive role against atherosclerosis. The aim of the present study was to evaluate the oxidizability of apolipoprotein B-containing lipoproteins, serum, and urinary paraoxonase/arylesterase activities in glomerulonephritis patients who had normal lipid parameters and creatinine levels. METHODS: Thirty-two patients with glomerulonephritis and 22 healthy controls were included in this study. A total of 32 patients (including nine with membranous GN, eight with immunoglobulin A nephropathy, eight with mesangial proliferative GN, five with focal-segmental glomerulosclerosis, one with diffuse proliferative GN, and one with minimal chance disease having biopsy proven GN) were enrolled into the study. We compared serum and urinary paraoxonase, arylesterase, serum lipids, urea, creatinine, hemoglobin, total protein and albumin values between groups. RESULTS: Serum urea, creatinine, total protein, albumin, uric acid, hemoglobin, and lipid parameters were similar in the glomerulonephritis and control groups (p > 0.05). PON1 activity was significantly lower in GN group than controls, but there was no statistically significant difference on arylesterase activity between groups. Oxidizability of apolipoprotein B-containing lipoproteins was significantly higher in GN group than controls. CONCLUSION: Our study shows that the findings of normal serum levels of creatinine, lipids, and proteins increased the oxidizability of apolipoprotein B-containing lipoproteins, and any decrease in PON1 activity in patients diagnosed with GN should be considered important. Hence, the immediate commencement of preventive as well as curative treatment in other to avoid the risk of cardiovascular and renal problems would be a correct approach.

Effect of indomethacin and selective cyclooxygenase-2 inhibitors on proteinuria and renal function in patients with AA type renal amyloidosis.

AIMS: Because the cardiovascular system (CVS) side-effects of cyclooxygenase-2 (COX-2) selective inhibitors have recently been questioned, we aimed to compare the renal and haemodynamic effects of cyclooxygenase selective (celecoxib and rofecoxib) and non-selective non-steroidal anti-inflammatory drugs (NSAIDs) (indomethacin) in patients with renal amyloidosis secondary to rheumatological diseases who required anti-inflammatory agents and are taking maximum tolerable dose of angiotensin-converting enzyme inhibitors. METHODS: The present study was performed on 11 patients with stable proteinuria who were diagnosed as AA amyloidosis secondary to rheumatological diseases confirmed by renal biopsies. The study had three consecutive stages (celecoxib 200 mg/day; indomethacin 100 mg/day; rofecoxib 25 mg/day.) Each was given for 4 weeks and a wash-out phase of 3 weeks was allowed between consecutive stages. RESULTS: Although the decrease of proteinuria in the celecoxib period was higher than in the rofecoxib and indomethacin periods, the difference was not statistically significant. No statistically significant differences were found between serum urea, creatinine, creatinine clearance and urinary sodium excretion. CONCLUSION: In this study, no differences were found between indomethacin and the two selective COX-2 inhibitors in respect to proteinuria and renal functions in 11 patients with renal amyloidosis secondary to rheumatological diseases with varying degrees of proteinuria. Routine doses of NSAIDs brought no additional benefit to the ACE inhibitor use in terms of proteinuria and renal functions. The use of selective COX-2 inhibitors should be limited to their anti-inflammatory and analgesic effects in this population.

Synchronous carcinomas of stomach and bladder together with AA amyloidosis.

Although the association and causality between chronic inflammatory states and systemic AA amyloidosis have been well established, the evidence linking solid malignancies to reactive AA amyloidosis is scarce. Here, a case of diagnosed AA amyloidosis associated with synchronous carcinomas of stomach and bladder complicated with nephrotic syndrome and renal failure is reported.

Relation between insulin resistance and serum concentrations of IL-6 and TNF-alpha in overweight or obese women with early stage breast cancer.

Insulin resistance (IR) and obesity may be risk factors for breast cancer. The mechanism of IR in patients with cancer has not been fully clarified yet. This study was conducted to evaluate the possible role of circulating cytokines; tumor necrosis factor-alpha (TNF-alpha) and interleukin 6 (IL-6) in inducing IR in 20 overweight or obese patients with early stage breast cancer and to compare their levels with that of body mass index matched 20 healthy controls. IR was calculated by homeostasis model assessment (HOMA) method. Four groups were formed according to a 2.7 HOMA-IR cut-off value as breast cancer with or without IR and controls with or without IR. IL-6 and HOMA-IR values were found to be higher in breast cancer patients with IR compared to other groups. There was no significant difference in TNF-alpha levels between groups. HOMA-IR values correlated with estradiol and IL-6 levels in all breast cancer patients but not TNF-alpha. HOMA-IR values, serum insulin, estradiol and IL-6 levels in the receptor positive group were significantly higher than those of the receptor negative group. These results suggested a possible contribution of endogenous IL-6 production and hyperinsulinemia to the development of breast cancer in overweight or obese patients with prominent IR.

Prevalence of transfusion transmitted virus infection and its effect on renal graft survival in renal transplant recipients.

OBJECTIVE: Little is known about the prevalence of transfusion transmitted virus (TTV) infection in renal transplant recipients (RTxs) and its effects on allograft survival. We investigated the prevalence of TTV and its effects on liver injury and graft survival in RTxs. MATERIAL AND METHODS: The study was performed in 33 consecutive RTxs (8 females, 25 males) and 100 blood donors (35 females, 65 males). A nested polymerase chain reaction was used to detect TTV DNA in serum. Serum creatinine and alanine aminotransferase (ALT) levels and 24-h protein excretion were determined in both TTV-positive and-negative patients. The total number of blood transfusions, the duration of hemodialysis and the total duration after transplantation were recorded in RTxs. In addition, hepatitis B surface antigen (HbsAg), anti-hepatitis C virus (HCV) and hepatitis G virus DNA antibodies were determined in all patients. RESULTS: TTV DNA was detected in 51.5% of RTxs and in 7% of the control group and this difference was statistically significant (p < 0.01). In the RTx group, 64.7% of TTV-positive and 56.2% of TTV-negative patients had undergone a previous blood transfusion. However, the blood transfusion replacement rate, total duration of dialysis therapy and posttransplant period did not differ between these two groups. Five (15.1%) patients in the RTx group had abnormal liver function tests (ALT >40 IU/l). Of these patients, 2 were anti-HCV-positive, 1 was HBsAg-positive and anti-HCV- plus TTV DNA-positive and the serologic tests of the remaining 2 patients were all negative. Among the TTV-positive patients, 2 (11.7%) were anti-HCV-positive, 1 (5.8%) was HBsAg-positive and 3 (17.6%) were HGV DNA-positive. The baseline serum creatinine levels did not differ significantly between the TTV-positive and-negative patients, being 1.5 +/- 0.6 and 1.4 +/- 0.6 mg/dl, respectively ( p > 0.05). Two of the TTV-positive patients and 1 of the TTV-negative patients had proteinuria. A 1-year follow-up of TTV-positive and-negative patients demonstrated neither acute nor chronic graft rejection. CONCLUSION: In RTxs, TTV infection was more prevalent than in the normal population. In our patients the virus did not have an important effect on renal graft rejection and did not cause liver injury. However, the question of whether TTV infection may affect graft survival requires further long-term investigation in larger groups.