scholarly journals MO177RENAL PROXIMAL  TUBULAR DISORDER AND RENAL FUNCTION LOSS IN HIV-INFECTED PATIENTS TREATED WITH TENOFOVIR DISOPROXIL FUMARATE

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Bingbin Zhao ◽  
Xiaoxiao Shi ◽  
Tiantian Ma ◽  
Jiaying Li ◽  
Peng Xia ◽  
...  
Keyword(s):  
Renal Function ◽  
Tubular Dysfunction ◽  
Proximal Tubular Dysfunction ◽  
Decline Rate ◽  
Proximal Tubular ◽  
The Impact ◽  
Annual Decline ◽  
Egfr Decline

Abstract Background and Aims Tenofovir disoproxil fumarate (TDF), as the most common antiviral drug, can cause both proximal tubular transportation dysfunctions and eGFR decline. The relationship between them is not clear due to lack of clinical data from large cohorts, especially in the Chinese population. In this study, we summarized the characteristics of proximal tubular injuries and eGFR decline in the cohort of HIV-infected patients treated with TDF, and explore the the impact of tenofovir on tubular transporters in vitro. Method We enrolled HIV-infected patients treated with TDF, who were regularly followed up in our hospital from Sep 1, 2001 to August 31, 2019. Their baseline and follow-up clinical data were collected. Proximal tubular dysfunction was defined as meeting two or more of the following criteria: hypophosphatemia, hypouricemia, low carbon dioxide binding capacity, positive urine glucose with normal plasma glucose level, and positive urine protein. Rapid deterioration of renal function was defined as the annual decline rate of eGFR exceeding 5ml/min/1.73m2. We also used human renal proximal tubular epithelial cell line (HK2) to further investigate the impact of tenofovir on transporters including SGLT2, NaPi-IIa, and URAT1 through immunofluorescence. Results A total of 375 HIV-infected patients receiving TDF were enrolled, mainly males (90.1%), with a median follow-up duration of 34(17, 58) months. The most common clinical manifestations were proteinuria (20.3%) and hypophosphatemia (12.3%). The prevalence of proximal tubular injury was 6.7%, which was significantly associated with low body weight, but was not associated with age, TDF course, baseline viral load, or baseline CD4+ T lymphocyte count. Their eGFR levels at the end of the follow-up were significantly lower than the baseline levels (104.6±15.2 vs. 110.6±14.2 ml/min/1.73m2, P<0.001). The average annual decline rate of eGFR was 5.0± 22.7 ml/min/1.73m2, and 23.6% of our patients had an annual decline rate of eGFR exceeding 5 ml/min/1.73m2. Rapid deterioration of renal function (≥ 5 ml/min/1.73m2 per year) was significantly associated with female but not related to proximal tubular dysfunction in multivariate logistic regression analysis. In vitro, the survival rate of HK2 cells was more than 95% when treated with tenofovir with a concentration of 1μmol/L for 48h. The expression levels of transporters (SGLT2, URAT1, and NaPi-IIa) were declined under the condition. Conclusion Among the HIV-infected Chinese patients treated with TDF, 6.7% had proximal tubular dysfunction and 23.6% showed accelerated annual decline rate of eGFR (≥ 5 ml/min/1.73m2 per year).

Prevalence of tubulopathy and association with renal function loss in HIV-infected patients

2019 ◽  
Vol 35 (4) ◽  
pp. 607-615 ◽  
Author(s):  
François-Xavier Lescure ◽  
Soraya Fellahi ◽  
Gilles Pialoux ◽  
Jean-Philippe Bastard ◽  
Anne-Line Eme ◽  
...  
Keyword(s):  
Tenofovir Disoproxil Fumarate ◽  
Screening Tools ◽  
Tubular Dysfunction ◽  
Glomerular Proteinuria ◽  
Proximal Tubular ◽  
Sub Saharan ◽  
Biochemical Testing ◽  
African Patients ◽  
The Impact ◽  
Egfr Decline

Abstract Background The incidence of chronic kidney disease (CKD) is 10 times higher in human immunodeficiency virus (HIV)-infected patients than in the general population. We explored the prevalence and determinants of proximal tubular dysfunction (PTD) in HIV-infected individuals, and assessed the impact of the tubulopathy on the estimated glomerular filtration rate (eGFR) outcome. Methods A cohort study was performed on 694 outpatients followed in a French centre to analyse the prevalence of PTD, the diagnosis performance of screening tools and the associated factors. eGFR was prospectively evaluated to analyse the predictive value of the tubulopathy on eGFR decrease. Results At inclusion, 14% of the patients presented with PTD and 5% with CKD. No individual tubular marker, including non-glomerular proteinuria, glycosuria dipstick or hypophosphataemia, registered sufficient performance to identify PTD. We found a significant interaction between tenofovir disoproxil fumarate exposure and ethnicity (P = 0.03) for tubulopathy risk. Tenofovir disoproxil fumarate exposure was associated with PTD in non-Africans [adjusted odds ratio (aOR) = 4.71, P < 10−3], but not in patients of sub-Saharan African origin (aOR = 1.17, P = 0.73). Among the 601 patients followed during a median of 4.3 years, 13% experienced an accelerated eGFR decline. Unlike microalbuminuria and glomerular proteinuria, tubulopathy was not associated with accelerated eGFR decline. Conclusion PTD is not rare in HIV-infected individuals but is less frequent in sub-Saharan African patients and is associated with tenofovir disoproxil fumarate exposure only in non-Africans. Its diagnosis requires multiple biochemical testing and it is not associated with an accelerated eGFR decline.

scholarly journals The growing pains of ifosfamide

2020 ◽  
Vol 13 (4) ◽  
pp. 500-503 ◽  
Author(s):  
Ben Sprangers ◽  
Sebastian Lapman
Keyword(s):  
Estimated Glomerular Filtration Rate ◽  
Kidney Injury ◽  
Tubular Dysfunction ◽  
Concomitant Treatment ◽  
Proximal Tubular Dysfunction ◽  
French Study ◽  
Growing Pains ◽  
Proximal Tubular

Abstract Ifosfamide is a commonly used chemotherapeutic known to have numerous adverse kidney manifestations. In this issue of Clinical Kidney Journal, Ensergueix et al. report a multicentric observational retrospective French study on 34 adult patients with tubular dysfunction and /or kidney dysfunction following ifosfamide treatment. Of these patients, 18% had isolated proximal tubular dysfunction, 14% had isolated acute kidney injury (AKI), 18% had isolated chronic kidney disease (CKD) and 50% had a combination of proximal tubular dysfunction and AKI. Concomitant treatment with cisplatin was identified as a risk factor for the development of AKI, and cisplatin and age were associated with estimated glomerular filtration rate at last follow-up. Interestingly, the cumulative dose of ifosfamide was not associated with renal outcomes. This report highlights the need for additional studies on the prevalence, spectrum and management of ifosfamide-associated nephrotoxicity and clearly demonstrates that patients who received ifosfamide should be followed long term to detect proximal tubular dysfunction and CKD early.

Serum metabolomics study of women with different annual decline rates of anti-Müllerian hormone: an untargeted gas chromatography–mass spectrometry-based study

2020 ◽  
Author(s):  
Nazanin Moslehi ◽  
Parvin Mirmiran ◽  
Rezvan Marzbani ◽  
Hassan Rezadoost ◽  
Mehdi Mirzaie ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Gas Chromatography ◽  
Pyroglutamic Acid ◽  
Gas Chromatography Mass Spectrometry ◽  
Ovarian Aging ◽  
Decline Rate ◽  
Fast Decline ◽  
Metabolomics Study ◽  
Annual Decline

Abstract STUDY QUESTION Which metabolites are associated with varying rates of ovarian aging, measured as annual decline rates of anti-Müllerian hormone (AMH) concentrations? SUMMARY ANSWER Higher serum concentrations of metabolites of phosphate, N-acetyl-d-glucosamine, branched chained amino acids (BCAAs), proline, urea and pyroglutamic acid were associated with higher odds of fast annual decline rate of AMH. WHAT IS KNOWN ALREADY Age-related rate of ovarian follicular loss varies among women, and the factors underlying such inter-individual variations are mainly unknown. The rate of ovarian aging is clinically important due to its effects on both reproduction and health of women. Metabolomics, a global investigation of metabolites in biological samples, provides an opportunity to study metabolites or metabolic pathways in relation to a physiological/pathophysiological condition. To date, no metabolomics study has been conducted regarding the differences in the rates of ovarian follicular loss. STUDY DESIGN, SIZE, DURATION This prospective study was conducted on 186 reproductive-aged women with regular menstrual cycles and history of natural fertility, randomly selected using random case selection option in SPSS from the Tehran Lipid and Glucose Study. PARTICIPANTS/MATERIALS, SETTING, METHODS AMH concentrations were measured at baseline (1999–2001) and the fifth follow-up examination (2014–2017), after a median follow-up of 16 years, by immunoassay using Gen II kit. The annual decline rate of AMH was calculated by dividing the AMH decline rate by the follow-up duration (percent/year). The women were categorized based on the tertiles of the annual decline rates. Untargeted metabolomics analysis of the fasting-serum samples collected during the second follow-up examination cycle (2005–2008) was performed using gas chromatography–mass spectrometry. A combination of univariate and multivariate approaches was used to investigate the associations between metabolites and the annual decline rates of AMH. MAIN RESULTS AND THE ROLE OF CHANCE After adjusting the baseline values of age, AMH and BMI, 29 metabolites were positively correlated with the annual AMH decline rates. The comparisons among the tertiles of the annual decline rate of AMH revealed an increase in the relative abundance of 15 metabolites in the women with a fast decline (tertile 3), compared to those with a slow decline (tertile 1). There was no distinct separation between women with slow and fast decline rates while considering 41 metabolites simultaneously using the principal component analysis and the partial least-squares discriminant analysis models. The odds of fast AMH decline was increased with higher serum metabolites of phosphate, N-acetyl-d-glucosamine, BCAAs, proline, urea and pyroglutamic acid. Amino sugar and nucleotide sugar metabolism, BCAAs metabolism and aminoacyl tRNA biosynthesis were among the most significant pathways associated with the fast decline rate of AMH. LIMITATIONS, REASONS FOR CAUTION Estimating the annual decline rates of AMH using the only two measures of AMH is the main limitation of the study which assumes a linear fixed reduction in AMH during the study. Since using the two-time points did not account for the variability in the decline rate of AMH, the annual decline rates estimated in this study may not accurately show the trend of the reduction in AMH. In addition, despite the longitudinal nature of the study and statistical adjustment of the participants’ ages, it is difficult to distinguish the AMH-related metabolites observed in this study can accelerate ovarian aging or they are reflections of different rates of the aging process. WIDER IMPLICATIONS OF THE FINDINGS Some metabolite features related to the decline rates of AMH have been suggested in this study; further prospective studies with multiple measurements of AMH are needed to confirm the findings of this study and to better understand the molecular process underlying variations in ovarian aging. STUDY FUNDING/COMPETING INTEREST(S) This study, as a part of PhD thesis of Ms Nazanin Moslehi, was supported by Shahid Beheshti University of Medical Sciences (10522-4). There were no competing interests. TRIAL REGISTRATION NUMBER N/A

Approach to the patient with renal Fanconi syndrome, glycosuria, or aminoaciduria

2018 ◽  
Author(s):  
Detlef Bockenhauer ◽  
Robert Kleta
Keyword(s):  
Fanconi Syndrome ◽  
Tubular Dysfunction ◽  
Renal Fanconi Syndrome ◽  
Renal Glycosuria ◽  
Proximal Tubular Dysfunction ◽  
Wide Range ◽  
Proximal Tubular ◽  
Proximal Tubular Function ◽  
Low Molecular Weight Proteins ◽  
Filtration Capacity

Up to 80% of filtered salt and water is returned back into the circulation in the proximal tubule. Several solutes, such as phosphate, glucose, low-molecular weight proteins, and amino acids are exclusively reabsorbed in this segment, so their appearance in urine is a sign of proximal tubular dysfunction. An entire orchestra of specialized apical and basolateral transporters, as well as paracellular molecules, mediate this reabsorption. Defects in proximal tubular function can be isolated (e.g. isolated renal glycosuria, aminoacidurias, or hypophosphataemic rickets) or generalized. In the latter case it is called the Fanconi–Debre–de Toni syndrome, based on the initial clinical descriptions. However, in clinical practice it is usually referred to as just the ‘renal Fanconi syndrome’. Severity of proximal tubular dysfunction can vary, and may coexist with some degree of loss of glomerular filtration capacity. Causes include a wide range of insults to proximal tubular cells, including a number of genetic conditions, drugs and poisons.

Unilateral nephrectomy and cisplatin as risk factors of ifosfamide-induced nephrotoxicity: analysis of 120 patients.

1994 ◽  
Vol 12 (1) ◽  
pp. 159-165 ◽  
Author(s):  
R Rossi ◽  
A Gödde ◽  
A Kleinebrand ◽  
M Riepenhausen ◽  
J Boos ◽  
...  
Keyword(s):  
Risk Factors ◽  
Renal Function ◽  
Unilateral Nephrectomy ◽  
Tubular Dysfunction ◽  
Schwartz Formula ◽  
Cytostatic Treatment ◽  
Fanconi’S Syndrome ◽  
Fractional Excretion Of Sodium ◽  
Proximal Tubular ◽  
Fanconi's Syndrome

PURPOSE This study was performed to identify risk factors of ifosfamide-induced renal damage. PATIENTS AND METHODS Renal function was assessed in 120 patients at a minimum of 3 months after completion of chemotherapy including ifosfamide. The cumulative ifosfamide dose ranged from 2 to 95 g/m2 (median, 30 g/m2). Ten patients had undergone unilateral nephrectomy; combination cytostatic treatment included cisplatin in 51 and methotrexate in 57. Sixty-eight patients had received gentamicin treatment. The glomerular filtration rate was estimated using the Schwartz formula. Proximal tubular function was assessed by the percent reabsorptions of glucose and 16 amino acids, the fractional excretion of sodium, and the fractional reabsorption of phosphate. In addition, the serum bicarbonate level was measured. RESULTS Proximal tubular dysfunction--with a predominance of renal amino acid (66.3%) and phosphate loss (38.3%)--was much more frequent than both glomerular impairment and acidosis. Seven patients were identified as having renal Fanconi's syndrome, and generalized tubulopathy was noted in another 15 patients. Ifosfamide-induced nephrotoxicity was dose-dependent, with a weak linear inverse correlation between cumulative ifosfamide dose and fractional phosphate reabsorption. Unilateral nephrectomy proved to be the single most important risk factor (odds ratio for the development of renal Fanconi's syndrome, 11.4), but cisplatin also significantly enhanced ifosfamide-mediated nephrotoxicity. Methotrexate, gentamicin, and patient age at primary diagnosis had no influence on renal function. CONCLUSION Ifosfamide chemotherapy should probably be restricted in patients after unilateral nephrectomy.

The Decline of Autophagy Contributes to Proximal Tubular Dysfunction During Sepsis

Shock ◽  
2012 ◽  
Vol 37 (3) ◽  
pp. 289-296 ◽  
Author(s):  
Hsiu-Wen Hsiao ◽  
Ke-Li Tsai ◽  
Li-Fang Wang ◽  
Yen-Hsu Chen ◽  
Pei-Chi Chiang ◽  
...  
Keyword(s):  
Tubular Dysfunction ◽  
Proximal Tubular Dysfunction ◽  
Proximal Tubular
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