Proficient Novel Biomarkers Guide Early Detection of Acute Kidney Injury: A Review

Jana, Sahadeb; Mitra, Palash; Roy, Suchismita

doi:10.3390/diseases11010008

Cited by 21 publications

(19 citation statements)

References 127 publications

(129 reference statements)

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“…As expected, minimal levels of albumin were found in urine of control littermates on the standard or HS diet. Next, to detect more subtle and specific evidence of epithelial cell injury in the nephron, we quantified message levels corresponding to the tubular injury marker, NGAL (50, 51), from whole kidney specimens. As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

Excess dietary sodium partially restores salt and water homeostasis caused by loss of the endoplasmic reticulum molecular chaperone, GRP170, in the mouse nephron

Porter,

Vorndran,

Marciszyn

et al. 2024

Preprint

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The maintenance of fluid and electrolyte homeostasis by the kidney requires proper folding and trafficking of ion channels and transporters in kidney epithelia. Each of these processes requires a specific subset of a diverse class of proteins termed molecular chaperones. One such chaperone is GRP170, which is an Hsp70-like, endoplasmic reticulum (ER)-localized chaperone that plays roles in protein quality control and protein folding in the ER. We previously determined that loss of GRP170 in the mouse nephron leads to hypovolemia, electrolyte imbalance, and rapid weight loss. In addition, GRP170-deficient mice develop an AKI-like phenotype, typified by tubular injury, elevation of clinical kidney injury markers, and induction of the unfolded protein response (UPR). By using an inducible GRP170 knockout cellular model, we confirmed that GRP170 depletion induces the UPR, triggers an apoptotic response, and disrupts protein homeostasis. Based on these data, we hypothesized that UPR induction underlies hyponatremia and volume depletion in rodents, but that these and other phenotypes might be rectified by supplementation with high salt. To test this hypothesis, control and GRP170 tubule-specific knockout mice were provided with a diet containing 8% sodium chloride. We discovered that sodium supplementation improved electrolyte imbalance and reduced clinical kidney injury markers, but was unable to restore weight or tubule integrity. These results are consistent with UPR induction contributing to the kidney injury phenotype in the nephron-specific GR170 knockout model, and that the role of GRP170 in kidney epithelia is essential to both maintain electrolyte balance and cellular protein homeostasis.

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Section: Resultsmentioning

confidence: 99%

Excess dietary sodium partially restores salt and water homeostasis caused by loss of the endoplasmic reticulum molecular chaperone, GRP170, in the mouse nephron

Porter,

Vorndran,

Marciszyn

et al. 2024

Preprint

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show abstract

“…Therefore, the significance between groups is more likely due to both the slight increase in HDL in the study group and the slight decrease in HDL in the control group. Increased creatinine and AST have been used in the diagnosis of kidney and liver injuries, respectively [ 39 , 40 ]. Therefore, the observed decrease in creatinine and AST is considered a favorable outcome.…”

Section: Discussionmentioning

confidence: 99%

Twelve-Week Safety and Potential Lipid Control Efficacy of Coffee Cherry Pulp Juice Concentrate in Healthy Volunteers

2023

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Coffee cherry pulp, a major waste product from coffee manufacturing, contains polyphenols with antioxidant activity. However, its clinical safety and health benefits are unclear. This randomized, double-blinded, placebo-controlled trial evaluated the safety and potential efficacy of coffee cherry pulp juice concentrate. A total of 61 participants were randomly divided into a study group (n = 30), receiving the juice, and a control group (n = 31), receiving a placebo drink of 14 g twice daily for 12 weeks. Adverse symptoms, changes in body weight, hematological and biochemical parameters, vital signs, and heart function were evaluated using subject diaries, interviews, blood and urine tests, and electrocardiograms. The results showed no intervention-related adverse events. Body weight, liver, renal function, complete blood counts, blood glucose, urinalysis, and electrocardiograms were not significantly altered throughout the study. Consuming the juice for at least 8 weeks significantly decreased cholesterol and LDL levels. The glucose levels were maintained significantly better than those of the placebo group. The findings suggest that continuously consuming 28 g/day of coffee pulp juice concentrate for 12 weeks is safe in healthy volunteers. Future studies could employ a dose of ≤28 g/day to investigate the efficacy of this novel food, especially for preventing dyslipidemia and diabetes.

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“…The most recently discovered biomarkers describing glomerular injury are nephrin, podocalyxin, podocin, netrin-1 or pyruvate kinase M2. Moreover, kidney injury molecule 1 (KIM-1), interleukin 18 (IL-18), neutrophil gelatinase-associated lipoocalcin (NGAL) or insulin-like growth factor binding protein 7 (IGFBP7) and urinary tissue inhibitor of metalloproteinases-2 (TIMP-2) are parameters of tubular and interstitial disorders [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Renal Disturbances during and after Radioligand Therapy of Neuroendocrine Tumors—Extended Analysis of Potential Acute and Chronic Complications

Saracyn¹,

Durma²,

Bober³

et al. 2023

IJMS

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Neuroendocrine tumors (NEN) are a group of neoplasms that arise from hormonal and neural cells. Despite a common origin, their clinical symptoms and outcomes are varied. They are most commonly localized in the gastrointestinal tract. Targeted radioligand therapy (RLT) is a treatment option which has proven to be successful in recent studies. However, the possible outcomes and true safety profile of the treatment need to be fully determined, especially by new, more sensitive methods. Our study aimed to present an extended analysis of acute and chronic renal complications during and after radioligand therapy using, for the first time in the literature, innovative and complex renal parameters. Forty patients with neuroendocrine tumors underwent four courses of radioligand therapy with [177Lu]Lu-DOTATATE or [177Lu]Lu/[90Y]Y-DOTATATE. Radioisotopes were administrated in intervals of 8–12 weeks, with concurrent intravenous nephroprotection. New detailed and sensitive renal parameters were used to determine the renal safety profile during and after radioisotope therapy for standard treatment of NEN. During the first and fourth courses of RLT, no change in the glomerular filtration rate (GFR) was observed. However, long-term observations one year after the treatment showed a 10% reduction in the GFR. During the first course of treatment, the fractional urea and calcium excretions increased, while the fractional potassium concentration decreased. The fractional calcium excretion remained highly increased in long-term observations. Decreases in urine IL-18, KIM-1 and albumin concentrations were observed during RLT. The concentrations of IL-18 and KIM-1 remained low even a year after therapy. The ultrasound parameters of renal perfusion changed during treatment, before partially returning to the baseline one year after therapy, and were correlated with the biochemical parameters of renal function. A permanent increase in diastolic blood pressure was correlated with the decrease in the GFR observed during the study. In this innovative and complex renal assessment during and after RLT, we found a permanent 10% per year decrease in the GFR and noticeable disturbances in renal tubule function. The diastolic blood pressure also increased.

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Proficient Novel Biomarkers Guide Early Detection of Acute Kidney Injury: A Review

Cited by 21 publications

References 127 publications

Excess dietary sodium partially restores salt and water homeostasis caused by loss of the endoplasmic reticulum molecular chaperone, GRP170, in the mouse nephron

Excess dietary sodium partially restores salt and water homeostasis caused by loss of the endoplasmic reticulum molecular chaperone, GRP170, in the mouse nephron

Twelve-Week Safety and Potential Lipid Control Efficacy of Coffee Cherry Pulp Juice Concentrate in Healthy Volunteers

Renal Disturbances during and after Radioligand Therapy of Neuroendocrine Tumors—Extended Analysis of Potential Acute and Chronic Complications

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