Renal toxicity with cumulative doses of cis-diamminedichloroplatinum-II in pediatric patients with osteosarcoma. Effect on creatinine clearance and methotrexate excretion

Abstract Bisphosphonates effectively reduce the number of skeletal-related events and relieve metastatic bone pain, improving quality of life in patients with malignant bone disease. However, clinical studies have highlighted that some, but not all intravenous (i.v.) bisphosphonates are associated with an increased risk of renal toxicity. The renal safety of bisphosphonates is particularly important in patients with multiple myeloma or in the elderly, who often have some degree of underlying renal damage and are at high risk of renal failure. In phase III trials, the renal safety profile of i.v. ibandronate was comparable to placebo. This agent may therefore be suitable for use in patients with impaired renal health. The current open-label study assessed the renal safety of ibandronate in elderly patients with multiple myeloma and varying stages of pre-existing renal impairment. Patients with multiple myeloma (creatinine clearance 8–139mL/min) received i.v. ibandronate (6mg, infused over 30 minutes). For each patient, deterioration in renal function was graded at baseline using creatinine clearance (grade 0: ≥80, 1: 50–79, 2: 30–49, 3: <30mL/min). Urinary markers of tubular damage (α-glutathione-S-transferase [α GST] and β-N-acetyl-glucosaminidase [βNAG]) were measured at baseline and at 24 and 72 hours following ibandronate infusion. Follow-up toxicity data was collected over 6 months for a subset of patients (n=6). A total of 29 patients (15 females and 14 males; mean age 71.1 ± 5 years) were included in this study. At baseline, four patients had a normal renal function (grade 0). The remaining 25 patients had varying degrees of renal insufficiency (grade 1: n=6, grade 2, n=8, grade 3: n=11). Mean proteinuria was 1799 ± 2140mg/24 hours. Serum creatinine and levels of urinary markers (α GST and βNAG) remained stable throughout the study. There was a statistically non-significant decrease in βNAG, and a positive correlation between ibandronate elimination and creatinine clearance. In the subset of six patients receiving six additional monthly infusions, ibandronate had no negative impact on renal function. To conclude, in this study of elderly patients with multiple myeloma, ibandronate was well tolerated and did not compromise renal health, despite 86% (25/29) of patients having pre-existing renal insufficiency. This was evidenced by markers of tubular damage and renal function, which remained unchanged throughout the study period. Furthermore, a subset of patients who received repeated ibandronate infusions did not experience renal toxicity. The management of drug-related nephrotoxicity needs special attention in patients with multiple myeloma, and in the elderly. These data suggest that ibandronate may be suitable for use in high risk multiple myeloma patients with pre-existing renal impairment. Further studies in larger groups of patients are warranted.

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Assessment of renal safety of tenofovir disoproxil fumarate in people living with HIV in Tunisia

The International Arabic Journal of Antimicrobial Agents ◽

10.3823/0811 ◽

2017 ◽

Vol 7 (3) ◽

Author(s):

Ikbel Kooli ◽

Mariem Ajroudi ◽

Abir Aouam ◽

Hajer Ben Brahim ◽

Adnene Toumi ◽

...

Keyword(s):

Creatinine Clearance ◽

Tenofovir Disoproxil Fumarate ◽

Fanconi Syndrome ◽

Renal Toxicity ◽

Small Sample Size ◽

Small Sample ◽

University Hospital ◽

People Living With Hiv ◽

Tubular Dysfunction ◽

Cross Sectional

Background: Tenofovir disoproxil fumarate (TDF) is a nucleotide reverse transcriptase inhibitor (NRTI). TDF is generally well tolerated. It is eliminated by the combination of glomerular filtration and active renal tubular secretion. Thus, it can be responsible, in the medium and long term, of renal toxicity. The aim of our study is to assess the prevalence of TDF nephrotoxicity and its factors risk in PLHIV treated in the Infectious Diseases Department at the University Hospital of Monastir, Tunisia.. Methods: An observational cross-sectional single-centre prospective study included 62 cases of HIV-infected patients taking antiretroviral therapy (ART) containing TDF was conducted between 1st August 2016 and 31 December 2016 at Fattouma Bourguiba University Hospital of Monastir, in Tunisia. During this period, patients were screened for renal dysfunction to detect renal toxicity, Tubular dysfunction or Fanconi syndrome. Results: 62 patients were included with female/male ratio at 1,52. The mean age was 39 years ± 8,5 years. Half of the patients were treated with TDF as first-line therapy. The average duration of TDF was 25 months, the duration was greater than 12 months in 40 (65%) patients. There was a decrease in creatinine clearance in 21 (33.8%) patients, the average of the decrease was 128,6 ±35,8 ml/min Proximal tubulopathy was noted in 1 patient (1.6%) and no patient had Fanconi syndrome. No risk factors for renal impairment under TDF were found. This finding could be explained by the small sample size Conclusion: TDF-related renal toxicity is often asymptomatic, it require early detection. In ours patient cases, TD is rare, but creatinine clearance decrease is frequent and may inform of possible TD in these patient. In order to reduce TDFtoxicity, a new pro-drug, tenofovir alafenamide (TAF), is now available.

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Suitable Dialytic Indicators for Pediatric Peritoneal Dialysis Patients: The Alternative to Creatinine Clearance

Peritoneal Dialysis International ◽

10.1177/089686080302300310 ◽

2003 ◽

Vol 23 (3) ◽

pp. 270-275 ◽

Cited By ~ 3

Author(s):

Kenji Ishikura ◽

Hiroshi Hataya ◽

Masahiro Ikeda ◽

Masataka Honda

Keyword(s):

Body Weight ◽

Peritoneal Dialysis ◽

Creatinine Clearance ◽

Pediatric Patients ◽

Stable Condition ◽

Stepwise Multiple Regression ◽

Mean Values ◽

Target Value ◽

Male Model ◽

Total Body

← Objective Owing to the discord between body weight and body surface area (BSA), creatinine clearance (CCr) is predisposed to be small in pediatric patients on peritoneal dialysis (PD). Alternatively, Kt/V creatinine (Kt/V creat), which is normalized to total body water (TBW) rather than BSA, could be a better dialytic indicator. In this study, the efficiency of dialysis and the nutritional status of pediatric patients on chronic PD were examined, and the utility of dialytic indicators was evaluated. ← Patients and Methods 49 patients under 20 years old, in stable condition, and on PD were analyzed. Weekly total Kt/V of urea (Kt/V urea), CCr, Kt/V creat, and normalized protein equivalent of nitrogen appearance (nPNA) were measured for all patients and for patients under 6 years old. The target value was 2.0/week for Kt/V urea and 60 L/week/1.73 m2 for CCr, as recommended by the Kidney Disease Outcomes Quality Initiative guidelines. The target value for Kt/V creat was set as 1.52/week, using a male model with a height of 170 cm and a body weight of 65 kg. ← Results The mean values of delivered Kt/V urea, CCr, Kt/V creat, and nPNA (and proportion of patients that achieved each target value) for all patients were 2.25 ± 0.57/week (67.4%), 53.8 ± 19.3 L/week/1.73 2m (26.5%), 1.83 ± 0.73/week (65.3%), and 1.11 ± 0.42 g/day, respectively. The values for patients under 6 years old were 2.38± 0.26/week (90.0%), 45.9 ± 12.8 L/week/1.73 2m (10.0%), 1.94 ± 0.51/week (90.0%), and 1.52 ± 0.67 g/day, respectively. Stepwise multiple regression analyses revealed that the relationship between CCr and Kt/V urea was affected by the patient's age. ← Conclusions Our pediatric patients achieved the recommended target value of Kt/V urea. At the same time, the nPNA results reflected the patient's status well. However, CCr appeared to be inappropriate as an indicator for patients under 6 years old. Kt/V creat is suggested to be a better dialytic indicator for these patients.

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First safety and response results of a randomized phase III study with liposomal platin in the treatment of advanced squamous cell carcinoma of the head and neck (SCCHN)

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.6040 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 6040-6040

Author(s):

C. F. Jehn ◽

S. Siebmann ◽

G. Pecher ◽

K. Wernicke ◽

K. Possinger ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Creatinine Clearance ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Renal Toxicity ◽

Phase Iii ◽

Advanced Squamous Cell Carcinoma ◽

Grade Ii ◽

Grade Iii

6040 Background: Cisplatin is one of the most active chemotherapeutic agents used in the treatment of advanced squamous cell carcinoma of the head and neck (SCCHN). However, its clinical efficacy is limited by its renal- and hematotoxicity profile. In a randomized, multicenter phase III trial, we replaced conventional cisplatin by a liposomal formulation of cisplatin (lipoplatin), and compared the safety and efficacy profiles of patients (pts) in the two treatment arms. Methods: Arm A: 100 mg/m2/d lipoplatin (d 1,8,15) plus 1,000 mg/m2/d 5-FU (d 1–5) q3w for 6 cycles; arm B: 100 mg/m2/d cisplatin (d 1) plus 1,000 mg/m2/d 5-FU (day 1–5) q3w for 6 cycles. Inclusion criteria: histologically confirmed SCCHN, age 18–75, renal function (creatinine clearance >50 ml/min) and primary metastatic disease or progressive SCCHN. Results: 62 pts were randomized, from which 43 pts (39 m; 4 w) were evaluable for outcome and toxicity. In the cisplatin arm hematotoxicity was more frequent (grades I/II: 28 pts, grades III/IV: 2 pts) than in the lipoplatin arm (grades I/II: 15 pts, grades III/IV: 3 pts). The rate of anemia was similar between the treatment arms. 13 pts in the lipoplatin arm experienced renal toxicity with (grade I: 3pts) and (grade II: 10 pts), as measured by a reduction of the creatinine clearance (grade I: 99–75 ml/min; grade II: 74–50 ml/min; grade III: <50 ml/min). Renal toxicity occurred in 8 patients in the cisplatin arm with 1 pt (grade I) and 3 pts (grade II), however 5 pts developed grade III. No renal toxicity grade III was developed in the lipoplatin arm until now. Outcome was as follows: lipoplatin arm: PR: 3 pts; SD: 13 pts; PD: 9 pts; cisplatin arm: PR: 8 pts; SD: 9 pts; PD: 1 pts. Thus, the non-PD pts (PR or SD) was 16/25 (64 %) in the lipoplatin arm vs 17/18 (94%) cases in the cisplatin arm. Conclusions: Liposomal platin seems to reduce both the renal and hematological toxicity as compared to conventional cisplatin to a clinically relevant extent. This reduction of side effects will influence the chance to preserve the dose density of chemotherapy, and thereby, the efficacy of treatment. No significant financial relationships to disclose.

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Renal Toxicity in Pediatric Patients Receiving Cidofovir for the Treatment of Adenovirus Infection

Journal of the Pediatric Infectious Diseases Society ◽

10.1093/jpids/pix011 ◽

2017 ◽

Vol 6 (4) ◽

pp. 399-402 ◽

Cited By ~ 18

Author(s):

Surabhi B Vora ◽

Adam W Brothers ◽

Janet A Englund

Keyword(s):

Pediatric Patients ◽

Renal Toxicity ◽

Adenovirus Infection

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Protective Effects of Vitamin C Concomitant Treatment on Deferasirox-induced Renal Toxicity in Rats

Journal of Arak University of Medical Sciences ◽

10.32598/jams.23.6.62.7 ◽

2021 ◽

Vol 23 (6) ◽

pp. 926-943

Author(s):

Taha Fereydouni ◽

◽

Saeed Hajihashemi ◽

Parsa Yousefichaijan ◽

Ali Rahbari ◽

...

Keyword(s):

Oxidative Stress ◽

Vitamin C ◽

Creatinine Clearance ◽

Renal Toxicity ◽

Renal Tissue ◽

Beta Thalassemia ◽

Renal Tubules ◽

Concomitant Treatment ◽

Protective Effects ◽

Antioxidant Power

Background and Aim: Deferasirox (Exjade) is an iron-chelating drug used in patients with beta-thalassemia major. Oxidative stress is among f the major causes of nephrotoxicity and its progression. Deferasirox, due to oxidative stress and increased cell apoptosis causes the dysfunction of renal tubules and renal toxicity. According to its antioxidant and anti-inflammatory properties, the present study explored the effect of vitamin C on deferasirox-induced kidney damage. Methods & Materials: This study was performed on 30 Wistar rats in 3 groups of control, deferasirox, and deferasirox plus vitamin C. To induce the nephrotoxicity, the intra-peritoneum injection of deferasirox (75 mg/kg/day) was used. After taking plasma from the blood samples of the explored rats, we determined the values of Cr, Na+, K+, Mg+, osmolality, and BUN in the obtained plasma and urine samples. The creatinine clearance, as well as the relative and absolute excretion of sodium and potassium, were also calculated. After separating the two kidneys, they were used for the histologic study with Hematoxylin and Eosin (H&E) staining, as well as Malondialdehyde (MDA) and Ferric Reducing Antioxidant Power (FRAP) biochemical studies. Ethical Considerations This study was approved by the Research Ethics Committee of Arak University of Medical Sciences (Code: IR.ARAKMU.REC.1396.309). Results: Cotreatment with deferasirox and vitamin C reduced renal tissue MDA and relative and absolute Na and K excretion and urine osmolarity; this method also increased creatinine clearance and renal tissue FRAP. Conclusion: The co-administration of vitamin C presented a significant protective effect on the renal toxicity induced by deferasirox. The protective property of deferasirox is because of the antioxidant impacts of vitamin C in reducing oxidative stress and lipid peroxidation.

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