Urine NGAL and KIM-1—Tubular Injury Biomarkers in Long-Term Survivors of Childhood Solid Tumors: A Cross-Sectional Study

Latoch, Eryk; Konończuk, Katarzyna; Muszyńska-Rosłan, Katarzyna; Taranta-Janusz, Katarzyna; Wasilewska, Anna; Szymczak, Edyta; Trochim, Justyna; Krawczuk‐Rybak, Maryna

doi:10.3390/jcm10030399

Cited by 10 publications

(15 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Most studies to date have focused specifically on AKI, and there are limited data on the utility of these biomarkers in late drug-induced nephrotoxicity [15]. In our previous studies on the association between urinary KIM-1 and NGAL levels and late renal toxicity, we showed that CCS had higher levels of both biomarkers, which was related to the cumulative dose of cisplatin and ifosfamide [16,17]. In this prospective cohort study, we focused on β-2-microglobulin and its applicability in accessing renal function in CCS.…”

Section: Discussionmentioning

confidence: 89%

Urinary Beta-2-Microglobulin and Late Nephrotoxicity in Childhood Cancer Survivors

Latoch

Konończuk

Taranta-Janusz

et al. 2021

JCM

Self Cite

View full text Add to dashboard Cite

The objectives of this study were to evaluate urinary beta-2-microglobulin (β2M) levels in long-term childhood cancer survivors and to establish its association with anticancer drug-induced nephrotoxicity. The study consisted of 165 childhood cancer survivors (CCS) who were in continuous complete remission. We reported that CCS had a significantly higher level of β2M (p < 0.001) and β2M/Cr. ratio (p < 0.05) than healthy peers. Among all participants, 24 (14.5%) had decreased eGFR (<90 mL/min/1.73 m2). A significant positive correlation between β2M/Cr. ratio and body mass index (coef. 14.48, p = 0.046) was found. Furthermore, higher levels of urinary β2M were detected among CCS with a longer follow-up time (over 5 years) after treatment. Subjects with decreased eGFR showed statistically higher urinary β2M levels (20.06 ± 21.56 ng/mL vs. 8.55 ± 3.65 ng/mL, p = 0.007) compared with the healthy peers. Twelve survivors (7.2%) presented hyperfiltration and they had higher urinary β2M levels than CCS with normal glomerular filtration (46.33 ± 93.11 vs. 8.55 ± 3.65 ng/mL, p = 0.029). This study did not reveal an association between potential treatment-related risk factors such as chemotherapy, surgery, radiotherapy, and the urinary β2M level. The relationship between treatment with abdominal radiotherapy and reduced eGFR was confirmed (p < 0.05). We demonstrated that urinary beta-2-microglobulin may play a role in the subtle kidney injury in childhood cancer survivors; however, the treatment-related factors affecting the β2M level remain unknown. Further prospective studies with a longer follow-up time are needed to confirm the utility of urinary β2M and its role as a non-invasive biomarker of renal dysfunction.

show abstract

Section: Discussionmentioning

confidence: 89%

Urinary Beta-2-Microglobulin and Late Nephrotoxicity in Childhood Cancer Survivors

Latoch

Konończuk

Taranta-Janusz

et al. 2021

JCM

Self Cite

View full text Add to dashboard Cite

show abstract

“…Twelve studies [ 27 – 38 ] met inclusion criteria for the review and were published between 1991 and 2021. Studies included data from hospitals in Finland [ 38 ], the Netherlands [ 31 , 34 , 37 ], Poland [ 36 ], Spain [ 28 ], Turkey [ 27 ], the UK [ 29 , 30 , 33 ] and the USA [ 32 , 35 ], although no one study contained data from more than one country. Five were cross-sectional studies [ 27 , 31 , 34 , 36 , 38 ], and seven were cohort studies [ 28 – 30 , 32 , 33 , 35 , 37 ].…”

Section: Resultsmentioning

confidence: 99%

Long-term cisplatin nephrotoxicity after childhood cancer: a systematic review and meta-analysis

Schofield,

Harcus,

Pizer

et al. 2023

Pediatr Nephrol

View full text Add to dashboard Cite

Background Cisplatin is a chemotherapeutic drug commonly used in the treatment of many childhood solid malignancies. It is known to cause long-term nephrotoxicity, most commonly manifesting as reduced glomerular filtration rate and hypomagnesaemia. Existing literature regarding the epidemiology of long-term nephrotoxicity in childhood cancer describes large variation in prevalence and risk factors. Objectives This study is to evaluate the prevalence of, and risk factors for, long-term cisplatin nephrotoxicity after treatment for childhood cancer. Study eligibility criteria Studies were eligible for inclusion if they: (i) evaluated participants treated with cisplatin who were diagnosed with cancer < 18 years of age; (ii) investigated any author-defined measure of nephrotoxicity; and (iii) performed this evaluation 3 or more months after cisplatin cessation. Studies whose scope was broader than this were included if appropriate subgroup analysis was performed. Results Prevalence of reduced glomerular filtration rate (GFR) ranged between 5.9 and 48.1%. Pooled prevalence of reduced GFR using studies with a modern consensus threshold of 90 ml/min/1.73 m2 was 29% (95% CI 0.0–58%). Prevalence of hypomagnesaemia ranged between 8.0 and 71.4%. Pooled prevalence of hypomagnesaemia was 37% (95% CI 22–51%). Substantial heterogeneity was present, with I2 statistics of 94% and 73% for reduced GFR and hypomagnesaemia respectively. All large, long-term follow-up studies described increased risk of reduced GFR with increasing cumulative cisplatin dose. Included studies varied as to whether cisplatin was a risk factor for proteinuria, and whether age was a risk factor for cisplatin nephrotoxicity. Limitations A wide range of study methodologies were noted which impeded analysis. No studies yielded data from developing health-care settings. No non-English studies were included, further limiting generalisability. Conclusions Both of the most common manifestations of long-term cisplatin nephrotoxicity have a prevalence of approximately a third, with increasing cumulative dose conferring increased risk of nephrotoxicity. Further work is needed to characterise the relationship between reduced GFR and hypomagnesaemia, investigate other risk factors and understand the interindividual variation in susceptibility to nephrotoxicity.

show abstract

“…KIM-1 is a major glycoprotein that is synthesized in low quantities in the proximal tubules of normal kidneys and released in large quantities in the urine upon ischemia or nephrotoxic injury, as well as in response to renal metabolic disturbance [ 34 , 35 ]. Indeed, KIM-1 is the most sensitive marker of tubular injury [ 35 , 36 ]. On the other hand, NGAL, also known as renal troponin, is normally produced by the loop of Henle and neutrophils at low, barely detectable levels.…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, NGAL, also known as renal troponin, is normally produced by the loop of Henle and neutrophils at low, barely detectable levels. However, urinary levels of NGAL are massively increased in response to tubular injury and inflammation [ 36 ]. Nephrin is another transmembrane protein that is normally released from podocytes, and its higher urinary levels indicate early glomerular damage and podocytopathies [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

Phloretamide Protects against Diabetic Kidney Damage and Dysfunction in Diabetic Rats by Attenuating Hyperglycemia and Hyperlipidemia, Suppressing NF-κβ, and Upregulating Nrf2

Al-Hussan,

Albadr,

Alshammari

et al. 2024

Pharmaceutics

View full text Add to dashboard Cite

Potent hypoglycemic and antioxidant effects were recently reported for the apple-derived phenolic compound phloretamide (PLTM). The renoprotective effects of this compound are yet to be shown. This study aimed to examine the potential of PLTM to prevent diabetic nephropathy in streptozotocin-induced diabetic rats and to examine the possible mechanisms of protection. Non-diabetic and STZ-diabetic male rats were treated orally by gavage with either the vehicle or with PTLM (200 mg/kg; twice/week) for 12 weeks. PTLM significantly increased urine volume and prevented glomerular and tubular damage and vacuolization in STZ-diabetic rats. It also increased creatinine excretion and reduced urinary albumin levels and the renal levels of kidney injury molecule-1 (KIM-1), 8-hydroxy-2′-deoxyguanosine (8-OHdG), neutrophil gelatinase-associated lipocalin (NGAL), and nephrin in the diabetic rats. PTLM also prevented an increase in the nuclear levels of NF-κβ, as well as the total levels of tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), caspase-3, and Bax in the kidneys of diabetic rats. These effects were associated with reduced serum levels of triglycerides, cholesterol, and low-density lipoprotein cholesterol. In both the control and diabetic rats, PTLM significantly reduced fasting plasma glucose and enhanced the renal mRNA and cytoplasmic levels of Nrf2, as well as the levels of Bcl2, superoxide dismutase (SOD), and glutathione (GSH). However, PTLM failed to alter the cytoplasmic levels of keap1 in diabetic rats. In conclusion, PTLM prevents renal damage and dysfunction in STZ-diabetic rats through its hypoglycemic and hypolipidemic activities, as well as through its antioxidant potential, which is mediated by activating the Nrf2/antioxidant axis.

show abstract

Urine NGAL and KIM-1—Tubular Injury Biomarkers in Long-Term Survivors of Childhood Solid Tumors: A Cross-Sectional Study

Cited by 10 publications

References 32 publications

Urinary Beta-2-Microglobulin and Late Nephrotoxicity in Childhood Cancer Survivors

Urinary Beta-2-Microglobulin and Late Nephrotoxicity in Childhood Cancer Survivors

Long-term cisplatin nephrotoxicity after childhood cancer: a systematic review and meta-analysis

Phloretamide Protects against Diabetic Kidney Damage and Dysfunction in Diabetic Rats by Attenuating Hyperglycemia and Hyperlipidemia, Suppressing NF-κβ, and Upregulating Nrf2

Contact Info

Product

Resources

About