Some Aspects of Nephrotoxicity of Paracetamol and Ketoprofen in Patients with Rheumathoid Arthritis

2016 ◽  
Vol 70 (3) ◽  
pp. 118-124
Author(s):  
Dejan Spasovski ◽  
Sonja Genadieva-Stavric ◽  
Tatjana Sotirova
Keyword(s):  
Colorimetric Method ◽  
Initial Therapy ◽  
Tubular Damage ◽  
Moderate Correlation ◽  
Time Intervals ◽  
Number Of Patients ◽  
Proximal Tubular ◽  
Proximal Tubular Damage

Abstract Introduction. To determine the effect of initial therapy with Paracetamol and Ketoprofen on glomerular and tubular integrity in rheumatoid arthritis (RA), to quantify nephrotoxicity of these two drugs by measurement of enzymuria, which correlates with the damage of tubular epithelium. Microalbuminuria is used as a marker for glomerular damage, and urine excretion of N-Acetyl-b-D-glucosaminidase (NAG) as an indicator of proximal tubular damage. Methods. Using colorimetric method for determination of NAG, and immunoturbidimetric method for microalbuminuria, samples of 70 participants were examined (35 RA patients treated with Paracetamol only, 35 RA patients treated with Ketoprofen). The follow-up was in 5 time-intervals in the course of 24 weeks. Results. There was a moderate correlation between NAG and microalbuminuria (r=0.16) in the group of patients treated with Paracetamol only, and a moderate correlation (r=0.28) in the group of patients treated with Ketoprofen. NAG enzymuria in size, by number of patients Registered, and time of appearance, was greater and appeared earlier in the Ketoprofen group compared to the Paracetamol group. Conclusions. Ketoprofen is more potent NAG inductor and provokes greater tubular enzymuria than Paracetamol. Results from our study confirm safety in use of Paracetamol and Ketoprofen in everyday clinical practice.

New insights into the mechanisms involved in renal proximal tubular damage induced in vitro by ochratoxin A

2004 ◽  
Vol 18 (1) ◽  
pp. 43-49 ◽  
Author(s):  
Alessandra Gennari ◽  
Patricia Pazos ◽  
Monica Boveri ◽  
Robert Callaghan ◽  
Juan Casado ◽  
...  
Keyword(s):  
Ochratoxin A ◽  
Tubular Damage ◽  
Proximal Tubular ◽  
Proximal Tubular Damage ◽  
Renal Proximal Tubular

Abstract 17182: Patterns of Discontinuation for Non-vitamin K Oral Anticoagulants in Atrial Fibrillation: Results From the ORBIT-AF II Registry

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Benjamin A Steinberg ◽  
DaJuanicia N Simon ◽  
Laine Thomas ◽  
Jack Ansell ◽  
Bernard J Gersh ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Clinical Practice ◽  
Vitamin K ◽  
Oral Anticoagulation ◽  
Oral Anticoagulants ◽  
Initial Therapy ◽  
Primary Reason ◽  
Rates Of Change ◽  
Number Of Patients

Background: Oral anticoagulation (OAC) is effective at preventing stroke in patients with atrial fibrillation (AF), yet warfarin is often poorly tolerated. Non-vitamin K oral anticoagulants (NOACs) are as or more effective as warfarin, yet their tolerance and persistence in clinical practice is not known. Methods: We assessed patterns of persistent OAC use among 2,345 AF patients starting on therapy in the ORBIT-AF II registry (71% starting on a NOAC, and 29% on warfarin). Results: By 6 months, 364 (22%) patients started on a NOAC had discontinued or changed initial therapy versus 143 (21%) started on warfarin initially (p=0.5). Among warfarin users, patients who switched or discontinued therapy were of similar age (median ages 72 and 74 vs. 74 for stable users, p=0.7) and CHA2DS2-VASc scores (mean 98 and 3.66 vs. 3.84, p=0.4). Among NOAC users, those who discontinued treatment were younger (median age 68 vs. 73 for those who switched and 72 for stable users; p=0.0004), and lower CHA2DS2-VASc scores (3.02 vs. 3.58 and 3.47, respectively; p=0.0008). The median time to change or discontinuation was more rapid in those started on a NOAC vs warfarin (97 days vs. 122 days, p=0.003). Among those on warfarin at baseline, 7.6% (n=52) were switched to a NOAC within 6 months, whereas transitions from NOAC to warfarin was 2.5% (n=42).Transitions among NOACs occurred in 9.8%, 3.2%, and 5.5% of patients on baseline dabigatran, rivaroxaban, and apixaban, respectively. Physician preference was the most common reason for both OAC and warfarin changes (Table). Drug cost was the primary reason for change of therapy in 15% of NOAC users (vs. 0 for warfarin). Conclusions: At 6-month follow-up, one in five newly started on OAC had discontinued or changed. These rates of change were similar among warfarin and NOAC treated patients. Cost concerns drove discontinuation in a modest number of patients, however, cost concerns were more prevalent in NOAC-treated patients.

A Randomized Phase II Study Comparing Consolidation With a Single Dose Of 90y Ibritumomab Tiuxetan (Zevalin®) (Z) Vs. Maintenance With Rituximab (R) For Two Years In Patients With Newly Diagnosed Follicular Lymphoma (FL) Responding To R-CHOP. Preliminary Results At 36 Months From Randomization

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 369-369 ◽  
Author(s):  
Armando Lopez-Guillermo ◽  
Miguel A. Canales ◽  
Ivan Dlouhy ◽  
Javier Briones ◽  
Dolores Caballero ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Initial Therapy ◽  
Phase 2 ◽  
Ibritumomab Tiuxetan ◽  
Advisory Committees ◽  
Phase 2 Trial ◽  
Number Of Patients ◽  
Grade 3 ◽  
Randomized Phase 2

Abstract Patients with FL can have long time of survival, but disease progression typically occurs 3-5 years after initial treatment. Consolidation with Z after initial therapy has shown to improve progression-free survival (PFS) mainly in the pre-R era, whereas maintenance with R also has demonstrated a substantial benefit in terms of PFS in patients treated with immunochemotherapy. In this setting, the Spanish intergroup PETHEMA/GELTAMO/GELCAB started a randomized phase 2 trial in order to compare the use of consolidation with Z vs. R maintenance in patients with FL responding to R-CHOP. From June 2008 to July 2010, 146 patients (66M/80F; median age, 55 years) were enrolled from 25 Spanish institutions in the randomized phase 2 trial ZAR2007 (ClinicalTrials.gov, number NCT00662948). Main inclusion criteria were: FL grade 1, 2 or 3a, age 18-75 years, stages II-IV and need of treatment according to modified GELF criteria. Patients with FL grade 3b or transformed to DLBCL were excluded. In addition, patients with platelet count <150x109/L or bone marrow infiltration>25% before randomization were also excluded. Main end-point of the trial was PFS from randomization. The distribution according to the FLIPI score was as follows: low-risk 14%, intermediate 47%, and high 39%. After R-CHOP, 124 patients in CR (n=56), CR[u] (13) or PR (55) were randomized 1:1 (stratified by response) to arm A (90Y ibritumomab tiuxetan 0.4 mCi/kg IV; total dose of 90Y was capped at 32 mCi) vs. arm B (1 infusion of R 375 mg/m2 every 8 weeks for 2 years). Sixty three (51%) patients were assigned to arm A (Z) and 61 (49%) to arm B (R). Twenty two patients were not randomized due to response <PR, low neutrophil or platelets counts or patient decision. After a median follow-up of 37 months from randomization (range, 26 to 56), 31 patients eventually progressed/relapsed with a 36-month PFS of 64% (95% confidence interval [CI] 52-76) for patients in arm A (consolidation with Z) (22 events) and 86% (95% CI 77-95) for patients in the R maintenance (9 events) (p=0.01; HR=0.38, 95%CI 0.17-0.83) as shown in the figure. The number of patients in PR after R-CHOP who reached CR during maintenance were 14 of 28 (50%) and 12 of 26 (46%) for arms A and B, respectively. Two patients developed transformation to DLBCL at 8 (arm A) and 39 months (arm B) after randomization. During the maintenance period, patients receiving Z showed grade 3-4 neutropenia in 6 of 63 cases and grade 3-4 thrombocytopenia in 5 of 63, whereas these figures were 1 of 61 and 0 of 61 (p=0.05) for patients in arm B, respectively. No unexpected late toxicities have been reported. Five patients have died during the follow-up due to the progression of lymphoma in all cases, with no differences between the arms (36-month OS, 98% vs. 95% for arms A and B, respectively). In conclusion, in patients with FL in response after R-CHOP, maintenance with R was superior to consolidation with Z in terms of PFS, with no differences in OS with the current follow-up. Disclosures: Lopez-Guillermo: Roche: Membership on an entity’s Board of Directors or advisory committees. Briones:F. Hoffmann-La Roche: Honoraria.

A COMPARISON OF THE EFFECTS OF PROXIMAL AND DISTAL TUBULAR DAMAGE ON THE ACTION OF DESOXYCORTICOSTERONE AND ALDOSTERONE

1957 ◽  
Vol 35 (1) ◽  
pp. 641-644
Author(s):  
T. F. Nicholson
Keyword(s):  
Left Kidney ◽  
Left Renal Artery ◽  
Tubular Damage ◽  
Normal Kidney ◽  
Significant Drop ◽  
Sodium Tartrate ◽  
Left Ureter ◽  
Proximal Tubular ◽  
Proximal Tubular Damage ◽  
Distal Tubules

The proximal tubules of the left kidney in dogs were damaged by the injection of 0.5% racemic sodium tartrate into the left renal artery. In other experiments the distal tubules were damaged by the injection of 0.05% mercuric chloride up the left ureter. In animals with proximal tubular damage, intravenous infusions of desoxycorticosterone or aldosterone which produced a significant drop in sodium excretion from the normal kidney had no effect on the amount of sodium excreted by the damaged kidney. In animals with distal tubular damage the effect of these hormones on the damaged kidney was as great as on the normal kidney.

scholarly journals Urinary excretion of carnitine as a marker of proximal tubular damage associated with platin-based antineoplastic drugs

2009 ◽  
Vol 25 (2) ◽  
pp. 426-433 ◽  
Author(s):  
M. Haschke ◽  
T. Vitins ◽  
S. Lude ◽  
L. Todesco ◽  
K. Novakova ◽  
...  
Keyword(s):  
Urinary Excretion ◽  
Tubular Damage ◽  
Antineoplastic Drugs ◽  
Proximal Tubular ◽  
Proximal Tubular Damage

scholarly journals Cytogenetic studies in untreated Hodgkin's disease

Blood ◽  
1991 ◽  
Vol 77 (6) ◽  
pp. 1298-1304 ◽  
Author(s):  
H Tilly ◽  
C Bastard ◽  
T Delastre ◽  
C Duval ◽  
M Bizet ◽  
...  
Keyword(s):  
Hodgkin's Disease ◽  
Chromosomal Abnormalities ◽  
Hodgkin’S Disease ◽  
Stage Iv ◽  
Poor Survival ◽  
T Cell Lymphomas ◽  
Number Of Patients ◽  
Structural Abnormalities

Very little data have been published on cytogenetic abnormalities in Hodgkin's disease (HD) and their correlation with clinicopathologic features are scanty. We have performed chromosomal analysis of lymph nodes from 60 previously untreated HD patients and obtained analyzable metaphases in 49 patients (82%). Chromosomal abnormalities were found in 33 patients (55%) but only 31 karyotypes could be, at least partially, described. Twenty-nine cases showed numerical abnormalities that involved all chromosomes with the exception of chromosomes 13 and Y, which were gained less frequently and lost more frequently than other chromosomes. Structural abnormalities were found in 30 cases, involving all chromosomes except Y. Chromosomal regions 12p11–13, 13p11– 13, 3q26–28, 6q15–16, and 7q31–35 were rearranged in more than 20% of the analyzable cases. No correlation was found between cytogenetic findings and initial characteristics. When compared with diffuse B-cell lymphomas, defects in regions 2p25 (P less than .01), 12p11–13 (P less than .01), 13p11–13 (P less than .01), 14p11 (P less than .01), 15p11– 13 (P less than .02), and 20q12–13 (P less than .05) were more frequent in HD. When compared with T-cell lymphomas, only defects in regions 12p12–13 (P less than .01) and 13p11–13 (P less than .01) were more frequent in HD. Failure to obtain analyzable metaphases was correlated with stage IV of the disease (P less than .05) and with a poor survival (P less than .01), but cytogenetic results showed no other correlation with clinical outcome. We conclude that molecular studies in HD should be focused on the short arms of chromosomes 12 and 13. Determination of the clinical significance of cytogenetic findings will require a larger number of patients and a longer follow-up period.

A COMPARISON OF THE EFFECTS OF PROXIMAL AND DISTAL TUBULAR DAMAGE ON THE ACTION OF DESOXYCORTICOSTERONE AND ALDOSTERONE

1957 ◽  
Vol 35 (8) ◽  
pp. 641-644 ◽  
Author(s):  
T. F. Nicholson
Keyword(s):  
Left Kidney ◽  
Left Renal Artery ◽  
Tubular Damage ◽  
Normal Kidney ◽  
Significant Drop ◽  
Sodium Tartrate ◽  
Left Ureter ◽  
Proximal Tubular ◽  
Proximal Tubular Damage ◽  
Distal Tubules

The proximal tubules of the left kidney in dogs were damaged by the injection of 0.5% racemic sodium tartrate into the left renal artery. In other experiments the distal tubules were damaged by the injection of 0.05% mercuric chloride up the left ureter. In animals with proximal tubular damage, intravenous infusions of desoxycorticosterone or aldosterone which produced a significant drop in sodium excretion from the normal kidney had no effect on the amount of sodium excreted by the damaged kidney. In animals with distal tubular damage the effect of these hormones on the damaged kidney was as great as on the normal kidney.

Follicular Non-Hodgkin Lymphoma Grade 3a and 3b Subtypes Exhibit Similar Clinical Behaviour and Treatment Outcome

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3777-3777 ◽  
Author(s):  
Jesse Shustik ◽  
Michael Quinn ◽  
Joseph M Connors ◽  
Randy D Gascoyne ◽  
Brian Skinnider ◽  
...  
Keyword(s):  
British Columbia ◽  
Performance Status ◽  
Initial Therapy ◽  
Front Line ◽  
Entire Cohort ◽  
Non Hodgkin Lymphoma ◽  
Number Of Patients ◽  
Cancer Agency ◽  
Grade 3

Abstract The clinical usefulness of separating follicular lymphoma (FL) grade 3 into FL grade 3A (FL3a) and 3B (FL3b) subtypes remains controversial. The relative aggressiveness of these two subtypes and their potential curability with anthracycline-based therapy continues to be debated. Discrepancies in the literature may be related to the relatively small number of patients in most series and to the variable inclusion of patients with a diffuse histologic component on biopsy, likely representing early transformation. We present a retrospective review of clinical characteristics and outcome in a large cohort of patients with FL3a and FL3b, as strictly defined by WHO diagnostic criteria. Patients Patients diagnosed with FL grade 3 in the province of British Columbia (BC) between the years 1982 and 2008 were identified through the BC Cancer Agency Lymphoid Cancer Database. A total of 161 patients with pathology available for central review were included for analysis, and were categorized as FL3a (n=139) or FL3b (n=22) using current WHO criteria. Cases containing a diffuse component on biopsy were excluded. Results Median age of the entire cohort was 63 years (range, 18–88). There were no significant differences in age, sex, stage, serum LDH levels, or number of extranodal sites between the subgroups. However, there was a trend toward worse performance status in patients with FL3b compared with FL3a (PS 2–4 27% vs. 12%, respectively; p=0.054). Overall, more patients in the FL3b subgroup had a high-intermediate or high-risk IPI score compared with patients in the FL3a subgroup (36% vs. 17%, p=0.028). A significantly higher number of patients with FL3b received an anthracycline-based regimen as front-line therapy (82% vs. 36%, p <0.001) and approximately one third of the entire cohort received rituximab. With a median follow-up of 38 months (range, 1–224), no difference in overall survival (OS) (p=0.79) or disease-specific survival (DSS) (p=0.38) was observed between FL3a and FL3b patients (see Figure below) (5-year OS, 72% vs. 70% and 5-year DSS, 77% vs. 70%, respectively). Analysis limited to the FL3a subgroup showed no OS advantage for patients who received an anthracycline-containing regimen as initial therapy compared with those who did not (p=0.24). Conclusions Overall no significant differences in clinical outcome were noted between patients with FL3a and FL3b. No plateau in the survival curves was seen, suggesting that neither subtype is curable even with the use of anthracycline-based therapy. This large retrospective analysis, which expands on an earlier cohort from the province of British Columbia, calls into question the clinical relevance of this histological grading designation. Figure Figure

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