scholarly journals The Effect of Ischemic-Reperfusion on Acute Kidney Injury Pathogenesis to the Glomerular Microscopic Appearance and Cystatin C Level in Wistar White Rat.

2019 ◽  
Vol 3 (1) ◽  
pp. 28-37
Author(s):  
Annisa Wimaulia Azlin ◽  
Rachmat Hidayat ◽  
Kemas Ya'kub Rahadiyanto

Acute kidney injury (AKI) is a sudden decrease of kidney function. The incidence of AKI is increasing every year. One of the causes of AKI is the lack of blood supply to the kidneys (prerenal). At the present time, there are not many studies that report unilateral ischemic-reperfusion (UIR) duration which can cause kidney damage especially glomerulus. The aim of this study is to determine the effect of UIR duration to glomerular microscopic appearance, GFR and cystatin C produced in Wistar white rats. This study was performed in vivo by using Post-test Only Control Group Design. Unilateral Ischemic-Reperfusion was administered on the rat’s left kidney and recovery was done according to specified time. After recovery time, rat’s blood was taken, the rat was euthanized, and its kidneys were taken and stained with Picrosirius Red coloring. The kidneys were observed by using OptiLED and the photos were analyzed with ImageJ software. Blood samples were tested by ELISA to measure the cystatin C levels and the levels were converted into Larrson formula to obtain Glomerular Filtration Rate. The level of cystatin C increased along with the longer duration of UIR and compared inversely proportional to GFR which decreased along with the rise of UIR duration. Cystatin C and GFR had a significant mean difference (p<0.05) with all groups, except for the duration of the UIR group <60 minutes. The percentage of collagen obtained fluctuated but the whole group which was carried out by UIR had a significantly different collagen amount (p <0.05) with the sham-operated group. The average glomerular picture showed the addition of collagen, Bowman's capsule thickening and vascular retraction. The longer duration of UIR will worsen the kidney function.   Keywords: Unilateral Ischemic-Reperfusion, Cystatin C. Glomerular Filtration Rate, Collagen Area Fraction, Glomerulus

2020 ◽  
Vol 20 (4) ◽  
pp. e312-317
Author(s):  
Folake M. Afolayan ◽  
Olanrewaju T. Adedoyin ◽  
Mohammed B. Abdulkadir ◽  
Olayinka R. Ibrahim ◽  
Sikiru A. Biliaminu ◽  
...  

Objectives: Serum creatinine levels are often used to diagnose acute kidney injury (AKI), but may not necessarily accurately reflect changes in glomerular filtration rate (GFR). This study aimed to compare the prevalence of AKI in children with severe malaria using diagnostic criteria based on creatinine values in contrast to cystatin C. Methods: This prospective cross-sectional study was performed between June 2016 and May 2017 at the University of Ilorin Teaching Hospital, Ilorin, Nigeria. A total of 170 children aged 0.5–14 years old with severe malaria were included. Serum cystatin C levels were determined using a particle-enhanced immunoturbidmetric assay method, while creatinine levels were measured using the Jaffe reaction. Renal function assessed using cystatin C-derived estimated GFR (eGFR) was compared to that measured using three sets of criteria based on creatinine values including the Kidney Disease: Improved Global Outcomes (KDIGO) and World Health Organization (WHO) criteria as well as an absolute creatinine cut-off value of >1.5 mg/dL. Results: Mean serum cystatin C and creatinine levels were 1.77 ± 1.37 mg/L and 1.23 ± 1.80 mg/dL, respectively (P = 0.002). According to the KDIGO, WHO and absolute creatinine criteria, the frequency of AKI was 32.4%, 7.6% and 16.5%, respectively. In contrast, the incidence of AKI based on cystatin C-derived eGFR was 51.8%. Overall, the rate of detection of AKI was significantly higher using cystatin C compared to the KDIGO, WHO and absolute creatinine criteria (P = 0.003, <0.001 and <0.001, respectively). Conclusion: Diagnostic criteria for AKI based on creatinine values may not indicate the actual burden of disease in children with severe malaria. Keywords: Biomarkers; Acute Kidney Injury; Renal Failure; Glomerular Filtration Rate; Cystatin C; Creatinine; Malaria; Nigeria.


2020 ◽  
Vol 105 (9) ◽  
pp. e8.2-e9
Author(s):  
Rachel Boys

AimRenal toxicity causes major morbidity following chemotherapy- abnormal iGFRs may be detected in up to 73.7% of patients.1 Creatinine is universally used as a biomarker to track fluctuating function and to calculate surrogate glomerular filtration rate (GFR) in the form of estimating equations.2 There is concern regarding the suitability of creatinine as a biomarker in this population, and it is proposed that cystatin C as a biomarker alone and also included in estimating equations may offer improved clinical suitability and accuracy.3MethodsIn this prospective, longitudinal study over a period of 18 months, 132 combined isotope GFR (iGFR), creatinine and cystatin C measurements were taken from 48 paediatric oncology patients at a Northern Children’s Hospital. Correlation and agreement analysis was performed for both individual biomarkers and estimating equations. Sensitivity data, along with ROC curve analysis was performed for all biomarkers and estimating equations. Data from three identified patients was isolated to examine individual patient variation over time.ResultsCreatinine identified only 1/32 patients with an abnormal iGFR (<90 ml/min/1.73 m2) compared to cystatin C which identified 12/32. Creatinine values and both estimating equations failed to change significantly over a period of declining iGFR though cystatin C did show a significant inverse increase (p<0.05). Bland Altman analysis for both the creatinine and combined equation showed poor agreement (mean difference -64 ml/min/1.3 m2 and -20 ml/min/1.73 m2 respectively). All biomarkers and equations showed poor sensitivity to detect an abnormal iGFR either below 70 ml/min/1.73 m2 or 90 ml/min/1.73 m2. A transformation factor applied to the equations significantly improved the sensitivity and clinical applicability of all equations. The data from three individual patients failed to reveal any significant intra-patient relationships.ConclusionData from this study cannot support the use of creatinine or cystatin C as a single biomarker to monitor renal function in children undergoing chemotherapy. Newer cystatin C and creatinine combined equations, whilst offering statistical superiority, do not offer the clinical superiority to replace iGFR or provide a tool for accurate dose calculations. A transformation factor can be applied to the results gained from the estimating equations to significantly improve the detection of abnormal iGFR, though work in other patient cohorts is needed to support this. Previous work also supported the use of a transformation factor, though application of their transformation factor to this current cohort failed to replicate the 100% sensitivity findings previously demonstrated4. Three patients were identified from the cohort and their paired iGFR and estimated GFR were monitored prospectively, over a period of approximately a year. Significant variation was observed between iGFR and eGFR at each time point for all three patients and therefore personalisation of GFR estimation from baseline iGFR and demographic data could not be proposed. This requires exploration in a larger cohort with the possible inclusion of additional baseline variables.ReferencesCRUK Survival trends over time in Children’s Cancers. 1.2015. https://www.cancerresearchuk.org/health-professional/cancer-statistics/childrens-cancers/survival#heading-Two Accessed 28th March 2019.NICE ( 2013) CG169 Acute kidney injury: Prevention, detection and management of acute kidney injury up to the point of renal replacement therapy.Barnfield, MC, Burniston, MT, Reid, U, et al. Cystatin C in assessment of glomerular filtration rate in children and young adults suffering from cancer. Nuclear Medicine Communications 2013;34:609–614.Dodgshun, AJ, Quinlan, C, Sullivan, MJ. Cystatin C based equation accurately estimates glomerular filtration rate in children with solid and central nervous system tumours: enough evidence to change practice? Pediatric Blood and Cancer 2016;63:1535–1538.


Nephron ◽  
2020 ◽  
Vol 144 (12) ◽  
pp. 655-661
Author(s):  
Mina Khorashadi ◽  
Remi Beunders ◽  
Peter Pickkers ◽  
Matthieu Legrand

Assessment of kidney function is primarily based on urine output and Creatinine (Cr)-based methods to estimate glomerular filtration rate (GFR). The latter is confounded as Cr is not exclusively filtered by the kidney and rises relatively late after the onset of acute kidney injury (AKI). This leads to delays in recognition of reduced kidney function and diagnosis of AKI, particularly in critically ill patients where kidney function can change rapidly. The gold standard methods of GFR determination, such as inulin or iohexol clearance, are labor intensive and unfeasible in acute clinical settings. Proenkephalin A 119–159 (PENK) has been intensively studied as a novel biomarker of kidney function. PENK belongs to the enkephalin peptide family and is freely filtrated in the glomerulus. Plasma PENK concentration appears to correlate strongly with GFR. Moreover, increased plasma PENK concentrations are found to be associated with long-term kidney outcomes and mortality. In this review, we summarize the role of PENK in assessment of kidney function and its capacity to predict various clinical outcomes.


2017 ◽  
Vol 16 (1) ◽  
Author(s):  
Azrina Md Ralib ◽  
Iqbalmunawwir Ab Rashid ◽  
Nur Aisyah Ishak ◽  
Suhaila Nanyan ◽  
Nur Fariza Ramly ◽  
...  

Introduction: Plasma Cystatin C (CysC) is as an early functional marker for acute kidney injury. Estimates of glomerular filtration rate using CysC (eGFRCysC) has been used in some clinical setting. We evaluated the utility of CysC and eGFRCysC in diagnosing acute kidney injury (AKI) and predicting death in critically ill patients with sepsis.  Materials and method: This is an interim analysis of single centre, prospective observational study of critically ill patients. Inclusion criteria were patients older than 18 years old with sepsis and procalcitonin > 0.5ng/ml. Plasma creatinine and CysC were measured on admission, and eGFRCysC. AKI was defined based on the plasma creatinine criteria of the KDIGO guideline.  Results: Thirty one patients were recruited so far, of which 13 (41.9%) had AKI and six died. CysC were higher in patients with AKI versus No AKI (p<0.001), and corresponding eGFRCysC were lower (p=0.006). CysC and eGFRCysC on ICU admission diagnosed AKI with an AUC of 0.88(0.72 to 1.00), and 0.79 (0.62 to 0.96), respectively. Both did not predict death (AUC 0.59 (0.31 to 0.87) and 0.59 (0.31 to 0.86), respectively). After adjusting for age and SOFA score, both CysC and eGFRCysC independently diagnosed AKI (OR 13 (1.5 to 115) and 1.03 (1.01 to 1.06), respectively). The ideal cut-off point for diagnosing AKI for CysC is 1.5 mg/dl (84% sensitivity and 89% specificity) and for eGFRCysC as 77 ml/min (72% sensitivity and 84% specificity).  Conclusion: Plasma CysC and its estimated GFR independently diagnosed AKI in critically ill patients with sepsis. We suggest the ideal cut-off points of 1.5 mg/dl and 77 ml/min which can be used in the clinical setting in this cohort of patients.


2019 ◽  
Vol 2 (3) ◽  
pp. 186-196
Author(s):  
Ahadi Aulia Rahman ◽  
Rachmat Hidayat ◽  
Sri Nita

Acute Kidney Injury (AKI) merupakan penurunan fungsi ginjal secara cepat. Penyebab AKI terbesar adalah iskemia/reperfusi yang memicu respon inflamasi dan menyebabkan kerusakan ginjal. Inflamasi merupakan respon proteksi dan perbaikan jaringan, namun dapat menyebabkan fibrosis yaitu jaringan normal digantikan oleh matriks ektraseluler seperti kolagen. Kerusakan yang terjadi pada bagian tubulointerstisial berpengaruh besar terhadap fungsi ginjal yang dapat diukur dengan GFR menggunakan cystatin C. Tujuan penelitian ini adalah untuk mengetahui pengaruh durasi iskemia-reperfusi terhadap gambaran seluler tubulointerstisial, kadar cystatin C dan GFR pada tikus Wistar serta korelasi antara gambaran seluler tubulointerstisial, kadar cystatin C dan GFR. Penelitian ini adalah penelitian eksperimental dengan desain posttest only with control group. Penelitian menggunakan 30 ekor tikus Wistar yang dilakukan di animal house dan laboratorium biomolekuler Fakultas Kedokteran Universitas Sriwijaya. Gambaran seluler tubulointerstisial, kadar cystatin C dan GFR dinilai dengan persentase fraksi area kolagen, ELISA dan rumus Larsson. Iskemia 30 menit dan reperfusi 14 hari 99,1% berpengaruh terhadap persentase fraksi area kolagen, iskemia 120 menit dan reperfusi 14 hari 98,8% berpengaruh terhadap kadar cystatin C serta 99,5% berpengaruh terhadap GFR. Terdapat korelasi yang signifikan antara persentase fraksi area kolagen dan kadar cystatin C (p=0,0001, r=0,901), serta GFR (p=0,0001, r=-0,834), lalu antara kadar cystatin C dan GFR (p=0,0001, r=-915). Durasi iskemia-reperfusi berpengaruh terhadap gambaran seluler tubulointerstisial, kadar cystatin C dan GFR serta terdapat korelasi antara gambaran seluler tubulointerstisial, kadar cystatin C dan GFR pada tikus Wistar.


2016 ◽  
Vol 5 (34) ◽  
pp. 1869-1871
Author(s):  
Davendra Kumar ◽  
Ajay Kumar Mishra ◽  
Jalees Fatima ◽  
Mehboob Subhani Siddiqui ◽  
Moidur Rehman

2015 ◽  
Vol 42 (2) ◽  
pp. 141-147 ◽  
Author(s):  
Carmen A. Peralta ◽  
Paul Muntner ◽  
Rebecca Scherzer ◽  
Suzanne Judd ◽  
Mary Cushman ◽  
...  

Background/Aims: Persons with occult-reduced estimated glomerular filtration rate (eGFR <60 ml/min/1.73 m2 detected by serum cystatin C but missed by creatinine) have high risk for complications. Among persons with preserved kidney function by creatinine-based eGFR (eGFRcreat >60 ml/min/1.73 m2), tools to guide cystatin C testing are needed. Methods: We developed a risk score to estimate an individual's probability of reduced eGFR by cystatin C (eGFRcys <60 ml/min/1.73 m2) in The Reasons for Geographic and Racial Differences in Stroke (REGARDS) study and externally validated in the Third National Health and Nutrition Examination Survey (NHANES III). We used logistic regression with Bayesian model averaging and variables available in practice. We assessed performance characteristics using calibration and discrimination measures. Results: Among 24,877 adults with preserved kidney function by creatinine, 13.5% had reduced eGFRcys. Older and Black participants, current smokers and those with higher body mass index, lower eGFRcreat, diabetes, hypertension and history of cardiovascular disease were more likely to have occult-reduced eGFR (p < 0.001). The final risk function had a c-statistic of 0.87 in REGARDS and 0.84 in NHANES. By risk score, 72% of occult-reduced eGFR cases were detected by screening only 22% of participants. Conclusions: A risk score using characteristics readily accessible in clinical practice can identify the majority of persons with reduced eGFRcys, which is missed by creatinine.


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