scholarly journals The Effect of Acetylcysteine on Renal Function in Experimental Models of Cyclophosphamide-and Ifosfamide-Induced Cystitis

2020 ◽  
Vol 14 (3) ◽  
pp. 150-162
Author(s):  
Lukasz Dobrek ◽  
Klaudia Nalik-Iwaniak ◽  
Kinga Fic ◽  
Zbigniew Arent

<b><i>Introduction</i></b>: Urotoxicity is a characteristic attribute of cy-clophosphamide and ifosfamide. Acetylcysteine is perceived as a uroprotective and possible nephroprotective compound. The purpose of the study was to assess the effect of acetylcysteine treatment on the morphology of the kidneys and the urinary bladder, and renal function in rats with cystitis induced by cyclophosphamide or ifosfamide. <b><i>Methods</i></b>: Cystitis was induced in rats belonging to groups 2 and 3, as well as 4 and 5, by five administrations of cyclophosphamide (75 mg/kg) or ifosfamide (80 mg/kg) respectively. Additionally, groups 3 and 5 received acetylcysteine (200 mg/kg). Group 1 was “sham treated” as a control. Upon conclusion of the experiment, the animals were euthanized and their kidneys and urinary bladders were collected for histopathological analysis. The assessment of renal function was based on classic nitrogen blood parameters (urea, creatinine, and uric acid), as well as proteinuria and cystatin C (CysC) and kidney injury molecule-1 (KIM-1) urinary concentrations, and their 24-hour elimination with urine. <b><i>Results</i></b>: Reduction of blood urea nitrogen and uric acid, and urinary pH with a significant increase of CysC and KIM-1 urinary concentrations, and their 24-hour elimination with urine were observed in groups 2 and 4. The acetylcysteine treatment did not cause a significant change of blood parameters, but significantly decreased 24-hour elimination of CysC and KIM-1 with urine, and accounted for alleviation of the histopathological abnormalities of urinary bladders, with no significant effects on the structure of the kidneys. <b><i>Conclusions</i></b>: Acetylcysteine used in the experimental model of cyclophosphamide- and ifosfamide-induced cystitis had a uroprotective effect and also reduced renal dysfunction, which suggests its potential use as a nephroprotective compound in cyclophosphamide/ifosfamide therapy.

2020 ◽  
Vol 13 (1) ◽  
pp. 21-31
Author(s):  
Lukasz Dobrek ◽  
Klaudia Nalik-Iwaniak ◽  
Zbigniew Arent

Background: Renal damage and dysfunction are possible complications of pharmacotherapy with ifosfamide (IF), which also manifests urotoxic properties. A routine drug used to reduce the risk of IF-induced cystitis is mesna. Compounds with effect expected to be similar to mesna include N-acetylcysteine (NAC). Objective: The objective of the paper was histopathological verification of the uroprotective effect of NAC and assessment of whether this effect is accompanied by a potential nephroprotective effect. Methods: The experiment was conducted on 3 groups: 1 – control, sham-treated rats, 2 – animals treated with 5 times the IF dose administered i.p. (50 mg/kg b.w.) and 3 – rats treated with 5 times the IF dose administered i.p. + NAC administered p.o. (200 mg/kg b.w.). The renal function was evaluated analysing classical and new protein parameters (cystatin C - CysC, kidney injury molecule-1 – KIM-1 and nephrin - NPH) in blood and urine. Furthermore, histopathological analysis of bladders and kidneys was carried out. Results: Treatment with IF resulted in the development of cystitis, with no significant histopathological disturbances in the kidneys, and caused an increase in concentration and 24-hour excretion of CysC, KIM-1 NPH in the urine. Additional NAC administration caused a reduction of the said biochemical disturbances as well as improvement of the histopathological image of the urinary bladders. Conclusion: The IF therapy caused cystitis and kidney dysfunction of functional tubulopathy and early glomerulopathy character. Additional administration of NAC entailed improvement in the urinary bladder morphology and renal function. NAC is, thus, a compound exerting both uro- and nephroprotective effects.


Lupus ◽  
2020 ◽  
pp. 096120332097904
Author(s):  
Eman Ahmed Hafez ◽  
Sameh Abd El-mottleb Hassan ◽  
Mohammed Abdel Monem Teama ◽  
Fatma Mohammed Badr

Objective Lupus nephritis (LN) is closely associated with hyperuricemia, and uric acid is considered a risk factor for renal involvement in systemic lupus erythematosus (SLE). This study aimed to examine the association between serum uric acid (SUA) level and LN development and progression in SLE patients with normal renal function. Methods A total of 60 SLE patients with normal renal function from Ain Shams University Hospital were selected and assigned to group 1 (30 patients with LN) and group 2 (30 patients without LN). All patients were subjected to history taking, clinical examination, disease activity assessment based on SLE disease activity index (SLEDAI) and renal SLEDAI (SLEDAI-R) scores, and laboratory investigations, including as SUA, complete blood count, blood urea nitrogen (BUN), serum creatinine, creatinine clearance, urine analysis, protein/creatinine ratio, 24-h urinary protein excretion, Antinuclear antibodies (ANA), anti-dsDNA antibody, and serum complement (C3, C4). Results Disease duration, SLEDAI score, and SUA level were higher in group 1 than in group 2 (p < 0.001). SUA level was positively correlated with SLEDAI and SLEDAI-R scores, proteinuria, urinary casts, renal biopsy class, disease activity and chronicity indices, BUN level, and serum creatinine level but was negatively correlated with creatinine clearance (p < 0.05). SUA was a predictor of LN development in SLE patients (sensitivity, 83.3%; specificity, 70%). Conclusion SUA is associated with the development of lupus nephritis in patients with normal kidney function also SUA in-dependently correlated with disease activity and chronicity in LN.


2013 ◽  
Vol 35 ◽  
pp. 567-572 ◽  
Author(s):  
Sanja Simic Ogrizovic ◽  
Suzana Bojic ◽  
Gordana Basta-Jovanovic ◽  
Sanja Radojevic ◽  
Jelena Pavlovic ◽  
...  

Objectives. Retrospective study was designed to examine the importance of tissue kidney injury molecule-1 (KIM-1) expression in predicting kidney function in sixty patients (27 males) aged 34.15 ± 12.23 years with different kidney diseases over three years after kidney biopsy.Materials and Methods. Tissue KIM-1 expression was determined immunohistochemically and KIM-1 staining was scored semiquantitatively, as well as tubulointerstitialis (TIN), inflammation, atrophy, and fibrosis. Kidney function (MDRD formula) and proteinuria/day were evaluated at the time of biopsy (GFR0) and 6, 12, 24, and 36 months later.Results. Significantly positive correlations between tissue KIM-1 expression and age (r=0.313), TIN inflammation (r=0.456), fibrosis (r=0.317), and proteinuria at 6 months (r=0.394) as well as negative correlations with GFR0 (r=−0.572), GFR6 (r=−0.442), GFR24 (r=−0.398), and GFR36 (r=−0.412) were found. Meanwhile, TIN inflammation was the best predictor of all measured kidney functions during three years, while tissue KIM-1 expression (P=0.016) was a predictor only at 6 months after biopsy.Conclusion. Tissue KIM-1 expression significantly predicts kidney function solely at 6 months after biopsy, when the effects of immune and nonimmune treatments are the strongest.


2020 ◽  
Vol 21 (15) ◽  
pp. 5490 ◽  
Author(s):  
Satoshi Washino ◽  
Keiko Hosohata ◽  
Tomoaki Miyagawa

Partial or complete obstruction of the urinary tract is a common and challenging urological condition caused by a variety of conditions, including ureteral calculi, ureteral pelvic junction obstruction, ureteral stricture, and malignant ureteral obstruction. The condition, which may develop in patients of any age, induces tubular and interstitial injury followed by inflammatory cell infiltration and interstitial fibrosis, eventually impairing renal function. The serum creatinine level is commonly used to evaluate global renal function but is not sensitive to early changes in the glomerular filtration rate and unilateral renal damage. Biomarkers of acute kidney injury are useful for the early detection and monitoring of kidney injury induced by upper urinary tract obstruction. These markers include levels of neutrophil gelatinase-associated lipocalin (NGAL), monocyte chemotactic protein-1, kidney injury molecule 1, N-acetyl-b-D-glucosaminidase, and vanin-1 in the urine and serum NGAL and cystatin C concentrations. This review summarizes the pathophysiology of kidney injury caused by upper urinary tract obstruction, the roles played by emerging biomarkers of obstructive nephropathy, the mechanisms involved, and the clinical utility and limitations of the biomarkers.


2019 ◽  
Vol 10 (1) ◽  
pp. 17-21
Author(s):  
Tafazzul Hussain ◽  
Musarrat Sultana ◽  
Syeda Amber Zaidi ◽  
Syed Saud Hasan ◽  
Mohsin Turab ◽  
...  

Objective: To determine the effect of Allopurinol & Febuxostat for the treatment of hyperuricemic patients & its influence on renal function by measuring serum creatinine level. Study Design & setting: The clinical trial was conducted at Dr. Ruth K M Pfau Civil Hospital, Karachi, during the period of September 2018 to March 2019 Methodology: 60 patients with sUA > 6.8 mg/dl were registered. A detailed history was taken, patient's baseline serum Uric Acid (sUA) & serum Creatinine were measured. Patients were divided into two groups to receive Allopurinol, 300 mg & Febuxostat 80 mg, daily for 90-days. The blood parameters were repeated at day 30 and 90. Results: Group-A (Allopurinol treated patients) baseline uric acid changed from mean 8.79 ± 0.98 mg/dl to 6.40 ± 0.86 mg/dl at day 90. In Group-B (Febuxostat treated patients) sUA baseline mean changed from 8.85 ± 0.97 mg/dl to 5.96 ± 0.68 mg/dl. Mean difference ± SD change of serum uric acid in Group-A was 2.39 ± 1.15 mg/dl and with Group-B it was 2.90 ± 0.87 mg/dl. Mean Serum Creatinine in Group-A changed from 1.54 ± 0.39 mg/dl to mean 1.48 ± 0.40 mg/dl compared with Group-B where it changed from 1.42 ± 0.30 mg/dl to 1.45 ± 0.31 mg/dl at day-90. Mean difference ± SD of serum Creatinine in Group-A was 0.11 ± 0.25 mg/dl & in Group-B it was, 0.03 ± 0.15 mg/dl. The above changes were statistically non-significant with p-value of 0.144. Conclusion: Allopurinol and Febuxostat treatment resulted in improvement of serum Uric Acid levels while maintaining their renal function


2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Sho Nishida ◽  
Yuji Hidaka ◽  
Mariko Toyoda ◽  
Kohei Kinoshita ◽  
Kosuke Tanaka ◽  
...  

Abstract Background The renal function of the remaining kidney in living donors recovers up to 60~70% of pre-donation estimated-glomerular filtration rate (eGFR) by compensatory hypertrophy. However, the degree of this hypertrophy varies from donor to donor and the factors related to it are scarcely known. Methods We analyzed 103 living renal transplantations in our institution and divided them into two groups: compensatory hypertrophy group [optimal group, 1-year eGFR ≥60% of pre-donation, n = 63] and suboptimal compensatory hypertrophy group (suboptimal group, 1-year eGFR < 60% of pre-donation, n = 40). We retrospectively analyzed the factors related to suboptimal compensatory hypertrophy. Results Baseline eGFRs were the same in the two groups (optimal versus suboptimal: 82.0 ± 13.1 ml/min/1.73m2 versus 83.5 ± 14.8 ml/min/1.73m2, p = 0.588). Donor age (optimal versus suboptimal: 56.0 ± 10.4 years old versus 60.7 ± 8.7 years old, p = 0.018) and uric acid (optimal versus suboptimal: 4.8 ± 1.2 mg/dl versus 5.5 ± 1.3 mg/dl, p = 0.007) were significantly higher in the suboptimal group. The rate of pathological chronicity finding on 1-h biopsy (ah≧1 ∩ ct + ci≧1) was much higher in the suboptimal group (optimal versus suboptimal: 6.4% versus 25.0%, p = 0.007). After the multivariate analysis, the pathological chronicity finding [odds ratio (OR): 4.8, 95% confidence interval (CI): 1.3–17.8, p = 0.021] and uric acid (per 1.0 mg/dl, OR: 1.5, 95% CI: 1.1–2.2, p = 0.022) were found to be independent risk factors for suboptimal compensatory hypertrophy. Conclusion Chronicity findings on baseline biopsy and higher uric acid were associated with insufficient recovery of the post-donated renal function.


2018 ◽  
Vol 478 ◽  
pp. 13-17 ◽  
Author(s):  
Peter Egli ◽  
Stefanie Aeschbacher ◽  
Matthias Bossard ◽  
Lucien Eggimann ◽  
Steffen Blum ◽  
...  

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