Using circulating O-sulfotyrosine in the differential diagnosis of acute kidney injury and chronic kidney disease

Abstract Background Sulfation of tyrosine, yielding O-sulfotyrosine, is a common but fixed post-translational modification in eukaryotes. Patients with increased circulating O-sulfotyrosine levels experience a faster decline in renal function with progression to end-stage renal disease (ESRD). In the present study, we measured serum O-sulfotyrosine levels in individuals with chronic kidney disease (CKD) and acute kidney injury (AKI) to explore its ability to differentiate AKI from CKD. Methods A total of 135 patients (20 with AKI and 115 with CKD) were recruited prospectively for liquid chromatography-mass spectrometry assessment of circulating O-sulfotyrosine. We also studied C57BL/6 mice with CKD after 5/6 nephrectomy (Nx). Blood samples were drawn from the tail vein on Day 1, 3, 5, 7, 14, 30, 60, and 90 after CKD. Serum separation and characterization of creatinine, blood urea nitrogen (BUN), and O-sulfotyrosine was performed. Thus, the time-concentration curves of the O-sulfotyrosine level demonstrate the variation of kidney dysfunction. Results The serum levels of O-sulfotyrosine were markedly increased in patients with CKD compared with AKI. Median O-sulfotyrosine levels in CKD patients versus AKI, respectively, were as follows:243.61 ng/mL(interquartile range [IQR] = 171.90–553.86) versus 126.55 ng/mL (IQR = 48.19–185.03, P = 0.004). In patients with CKD, O-sulfotyrosine levels were positively correlated with creatinine, BUN, and Cystatin C (r = 0.63, P < 0.001; r = 0.49, P < 0.001; r = 0.61, P < 0.001, respectively) by the multivariate linear regression analysis (β = 0.71, P < 0.001; β = 0.40, P = 0.002; β = 0.73, P < 0.001, respectively). However, this association was not statistically significant in patients with AKI (r = − 0.17, P = 0.472; r = 0.11, P = 0.655; r = 0.09, P = 0.716, respectively). The receiver operating characteristic (ROC) analysis illustrated that the area under the curve was 0.80 (95% confidence interval [CI] 0.71–0.89; P < 0.001) and the optimal cut-off value of serum O-sulfotyrosine suggesting AKI was < 147.40 ng/mL with a sensitivity and specificity of 80.90 and 70.00% respectively. In animal experiments, serum levels of O-sulfotyrosine in mice were elevated on Day 7 after 5/6 nephrectomy (14.89 ± 1.05 vs. 8.88 ± 2.62 ng/mL, P < 0.001) until Day 90 (32.65 ± 5.59 vs. 8.88 ± 2.62 ng/mL, P < 0.001). Conclusion Serum O-sulfotyrosine levels were observed correlated with degrading renal function and in CKD patients substantially higher than those in AKI patients. Thus serum O-sulfotyrosine facilitated the differential diagnosis of AKI from CKD.

Download Full-text

Acute kidney injury pathology and pathophysiology: a retrospective review

Clinical Kidney Journal ◽

10.1093/ckj/sfaa142 ◽

2020 ◽

Author(s):

Joseph P Gaut ◽

Helen Liapis

Keyword(s):

Chronic Kidney Disease ◽

Acute Kidney Injury ◽

Renal Function ◽

Kidney Disease ◽

Renal Biopsy ◽

Retrospective Review ◽

Patient Management ◽

Kidney Injury ◽

High Morbidity ◽

Underlying Pathology

Abstract Acute kidney injury (AKI) is the clinical term used for decline or loss of renal function. It is associated with chronic kidney disease (CKD) and high morbidity and mortality. However, not all causes of AKI lead to severe consequences and some are reversible. The underlying pathology can be a guide for treatment and assessment of prognosis. The Kidney Disease: Improving Global Outcomes guidelines recommend that the cause of AKI should be identified if possible. Renal biopsy can distinguish specific AKI entities and assist in patient management. This review aims to show the pathology of AKI, including glomerular and tubular diseases.

Download Full-text

Effect of Chronic Kidney Disease on Outcome of Adult Patient Admitted With Hyperthyroidism: Analysis of the National Inpatient Sample 2016–2017

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.580 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A285-A286

Author(s):

Hafeez Shaka ◽

Iriagbonse Asemota ◽

Emmanuel Akuna ◽

Ehizogie Edigin ◽

Genaro Velazquez ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Acute Kidney Injury ◽

Kidney Disease ◽

Cardiogenic Shock ◽

Thyroid Dysfunction ◽

Linear Regression Analysis ◽

Kidney Injury ◽

National Inpatient Sample ◽

Inpatient Mortality ◽

Icd 10

Abstract Introduction: Kidney and thyroid function and dysfunction are interrelated through several mechanisms. Thyroid hormones can also have significant impact on kidney disease so it is important to consider the physiological association of thyroid dysfunction in relation to chronic kidney disease (CKD). Research shows that hyperthyroidism is usually not associated with CKD but is known to accelerate it. We sought to determine the effect of chronic kidney disease on patient admitted with hyperthyroidism. Methods: We queried the National Inpatient Sample (NIS) databases from 2016 to 2017 for adults aged 18 and above with hyperthyroidism as a principle diagnosis with and without hypertriglyceridemia using ICD-10 codes. Multivariate logistic and linear regression analysis was used accordingly to adjust for confounders Results: There were over 71 million discharges in the combined 2016 and 2017 NIS database. Out of 17,705 hyperthyroidism hospitalizations, 4% had chronic kidney disease. Chronic kidney disease with hyperthyroidism had a similar odd of inpatient mortality (AOR 0.79, CI 0.34–4.52, P= 0.787) and cardiogenic shock (AOR 2.66, CI 0.35–20.50, P=0.347). There was a statistically significant increase in odds of acute kidney injury (AOR 2.77, CI 1.60- 4.80, P <0.001) in those hospitalized with hyperthyroidism and chronic kidney disease compared to those with hyperthyroidism alone Conclusion: Chronic kidney disease is associated with similar odds of hospital mortality and cardiogenic shock among patients hospitalized for hyperthyroidism with increased odds of acute kidney injury compared to those without hyperthyroidism. It is very important to consider all clinical features and thyroid manifestations in those patients with CKD.

Download Full-text

MO423PROENKEPHALIN AS A BIOMARKER OF KIDNEY FILTRATION IN ACUTE KIDNEY INJURY

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab083.0015 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Camila Lima ◽

Etienne Macedo

Keyword(s):

Acute Kidney Injury ◽

Regression Analysis ◽

Kidney Disease ◽

Linear Regression ◽

Serum Creatinine ◽

Linear Regression Analysis ◽

Kidney Injury ◽

Multivariate Linear Regression Analysis ◽

Serum Cystatin ◽

Blood Samples

Abstract Background and Aims In the last decades, clinical research biomarker (BM) to improve assessment of kidney function have been intensive, and proenkephalin (PENK) has been identified as a new BM of filtration. We hypothesized whether PENK would have a better accuracy for the diagnosis of severe AKI than serum cystatin (CYS) and the serum creatinine (Scr). We evaluate patient in the peri op of liver transplant (LT). Method Blood samples were collected during the pre and post (until 48 hours) operative (op.) period of LT in 57 eligible patients. Where was analyzed PENK (Sphingotest®), CYS (Milipex) and Scr (Quimioluminence). AKI diagnosis was based on the Kidney Disease International Global Outcomes (KDIGO) criteria using Scr. KDIGO 1 was subclassified according to the International Club of Ascites (ICA). Results Of the 57 patients undergoing LT, 50 (88%) developed AKI according to the KDIGO criteria in the first week after LT. Twenty-one patients without AKI and with KDIGO 1-A (37%) were summarized as the no AKI/mild AKI group, whereas 36 patients with KDIGO 1-B, 2 and 3 (63%) were summarized as the severe AKI group. Before the intra - operative insult only PENK was significantly higher in patients that developed severe AKI, median 55 [P25-75(44,25 – 94,55)] in no AKI/mild AKI versus 90,16 [P25-75(64,70 – 135,76)] pmol/l in severe AKI p 0,021, an AUC 0,685 (CI 0,536 – 0,833), with a cutoff 55 pmol/l, sensibility of 0,86 and specificity 0,52, accuracy 0,75 to severe AKI. Scr levels in pre-op. were non- significantly higher in severe AKI; p=0,088. The CYS in the pre-op was similar within the groups. Pos-operative 48 hours after LT, PENK was significantly higher in severe AKI, median 81 [P25-75(61,25 – 101,50)] versus 161,45 [P25-75(122,85 – 294,03)] in severe AKI - p <0,0001 an AUC 0,83 (CI 0,72 - 0,94) with a cutoff 119,05 pmol/l, sensibility of 0,80 and specificity 0,90, accuracy 0,84 to severe AKI. Scr levels in post-op achieve an AUC 0,77 (CI 0,63 - 0,92) with a cutoff 1,49mg/dl, sensibility of 0,94, specificity 0,67 and accuracy 0,82. In a multivariate linear regression analysis adjusted for age, anestesia time, urine output and fluid balance, the PENK only was independently associated of severe AKI in pre-op. with OR 4,40 (CI 1,40 – 13,88) – p0,001 and the post-op. with OR 44,64 (CI 5,40 – 368,5) – p<0,0001. Conclusion PENK is a promisor filtration biomarker and showed a better acuracy to severe AKI in pre-operative than standard AKI diagnostic by Scr. Prediction of severe AKI in pre-operative period by PENK can help the management of these patients in the future.

Download Full-text

Star fruit intoxication leading to acute kidney injury

Bangladesh Medical Journal Khulna ◽

10.3329/bmjk.v48i1-2.27099 ◽

2016 ◽

Vol 48 (1-2) ◽

pp. 37-39 ◽

Cited By ~ 1

Author(s):

Md Arshad Ul Azim ◽

Abdus Salam

Keyword(s):

Chronic Kidney Disease ◽

Acute Kidney Injury ◽

Renal Function ◽

Kidney Disease ◽

Normal Renal Function ◽

Case Reports ◽

Kidney Injury ◽

Young Male ◽

Star Fruit ◽

Oxalate Nephropathy

There are few case reports regarding star fruit's nephrotoxicity and neurotoxicity in chronic kidney disease patients. Recently cases are found in people with normal renal function Star fruit nephrotoxicity is believed to be due to its high oxalate content which causes acute obstructive oxalate nephropathy. A neurotoxin (caramboxin) present in the fruit is responsible for neurotoxic features. Here we present a young male who developed acute kidney injury following star fruit ingestion in empty stomach. After admission, patient was treated conservatively and recovered completely.Bang Med J (Khulna) 2015; 48 : 37-39

Download Full-text

Impact on Outcomes across KDIGO-2012 AKI Criteria According to Baseline Renal Function

Journal of Clinical Medicine ◽

10.3390/jcm8091323 ◽

2019 ◽

Vol 8 (9) ◽

pp. 1323 ◽

Cited By ~ 3

Author(s):

Isabel Acosta-Ochoa ◽

Juan Bustamante-Munguira ◽

Alicia Mendiluce-Herrero ◽

Jesús Bustamante-Bustamante ◽

Armando Coca-Rojo

Keyword(s):

Chronic Kidney Disease ◽

Acute Kidney Injury ◽

Renal Function ◽

Kidney Disease ◽

Hospital Mortality ◽

Kidney Injury ◽

Clinical Syndrome ◽

Increment Rate ◽

Associated Risk Factors ◽

Baseline Renal Function

Acute kidney injury (AKI) and Chronic Kidney Disease (CKD) are global health problems. The pathophysiology of acute-on-chronic kidney disease (AoCKD) is not well understood. We aimed to study clinical outcomes in patients with previous normal (pure acute kidney injury; P-AKI) or impaired kidney function (AoCKD) across the 2012 Kidney Disease Improving Global Outcomes (KDIGO) AKI classification. We performed a retrospective study of patients with AKI, divided into P-AKI and AoCKD groups, evaluating clinical and epidemiological features, distribution across KDIGO-2012 criteria, in-hospital mortality and need for dialysis. One thousand, two hundred and sixty-nine subjects were included. AoCKD individuals were older and had higher comorbidity. P-AKI individuals fulfilled more often the serum creatinine (SCr) ≥ 3.0× criterion in AKI-Stage3, AoCKD subjects reached SCr ≥ 4.0 mg/dL criterion more frequently. AKI severity was associated with in-hospital mortality independently of baseline renal function. AoCKD subjects presented higher mortality when fulfilling AKI-Stage1 criteria or SCr ≥ 3.0× criterion within AKI-Stage3. The relationship between mortality and associated risk factors, such as the net increase of SCr or AoCKD status, fluctuated depending on AKI stage and stage criteria sub-strata. AoCKD patients that fulfil SCr increment rate criteria may be exposed to more severe insults, possibly explaining the higher mortality. AoCKD may constitute a unique clinical syndrome. Adequate staging criteria may help prompt diagnosis and administration of appropriate therapy.

Download Full-text

Increased progression to kidney fibrosis after erythropoietin is used as a treatment for acute kidney injury

AJP Renal Physiology ◽

10.1152/ajprenal.00241.2013 ◽

2014 ◽

Vol 306 (6) ◽

pp. F681-F692 ◽

Cited By ~ 24

Author(s):

Glenda C. Gobe ◽

Nigel C. Bennett ◽

Malcolm West ◽

Paul Colditz ◽

Lindsay Brown ◽

...

Keyword(s):

Oxidative Stress ◽

Chronic Kidney Disease ◽

Acute Kidney Injury ◽

Renal Function ◽

Kidney Disease ◽

Kidney Injury ◽

Renal Ischemia ◽

Acute Injury

Treatment of renal ischemia-reperfusion (IR) injury with recombinant human erythropoietin (rhEPO) reduces acute kidney injury and improves function. We aimed to investigate whether progression to chronic kidney disease associated with acute injury was also reduced by rhEPO treatment, using in vivo and in vitro models. Rats were subjected to bilateral 40-min renal ischemia, and kidneys were studied at 4, 7, and 28 days postreperfusion for renal function, tubular injury and repair, inflammation, and fibrosis. Acute injury was modulated using rhEPO (1,000 or 5,000 IU/kg, intraperitoneally) at the time of reperfusion. Renal tubular epithelial cells or fibroblasts in culture were subjected to hypoxia or oxidative stress, with or without rhEPO (200 IU/ml), and fibrogenesis was studied. The results of the in vivo model confirmed functional and structural improvement with rhEPO at 4 days post-IR ( P < 0.05). At 7 days post-IR, fibrosis and myofibroblast stimulation were increased with IR with and without rhEPO ( P < 0.01). However, at 28 days post-IR, renal fibrosis and myofibroblast numbers were significantly greater with IR plus rhEPO ( P < 0.01) compared with IR only. Mechanistically, rhEPO stimulated profibrotic transforming growth factor-β, oxidative stress (marker 8-hydroxy-deoxyguanosine), and phosphorylation of the signal transduction protein extracellular signal-regulated kinase. In vitro, rhEPO protected tubular epithelium from apoptosis but stimulated epithelial-to-mesenchymal transition and also protected and activated fibroblasts, particularly with oxidative stress. In summary, although rhEPO was protective of renal function and structure in acute kidney injury, the supraphysiological dose needed for renoprotection contributed to fibrogenesis and stimulated chronic kidney disease in the long term.

Download Full-text

Evaluation of renal function in primary care

Progress in Health Sciences ◽

10.5604/01.3001.0012.8347 ◽

2018 ◽

Vol 8 (2) ◽

pp. 202-205

Author(s):

B. Musiałowska ◽

M. Rudzińska ◽

E. Koc-Żórawska ◽

M. Żórawski

Keyword(s):

Primary Care ◽

Chronic Kidney Disease ◽

Acute Kidney Injury ◽

Renal Function ◽

Kidney Disease ◽

Chronic Diseases ◽

Kidney Injury ◽

Treatment Monitoring ◽

Primary Care Patients ◽

Drug Doses

Evaluation of renal function is one of the primary tools used in treatment and monitoring kidney injury such as acute kidney injury (AKI) or chronic kidney disease (CKD) in Primary Care patients. Accompanying chronic diseases also have an impact on the assessment of renal function, treatment monitoring and adjustment of drug doses.

Download Full-text