ABSTRACT
Background & objectives: Activation of renin-angiotensin system and tubulointerstitial damage might be seen in pre-albuminuria stage of diabetic nephropathy (DN). Here, diagnostic utility of four urinary biomarkers [Angiotensinogen (Angio), Interleukin (IL)-18, Neutrophil Gelatinase-Associated Lipocalin (NGAL) and Cystatin] during pre-albuminuria stages of non-hypertensive type 2 diabetes patients was studied. Methods: A total of 952 type 2 diabetes mellitus (T2DM) patients were screened for nephropathy [estimated glomerular filtration rate (eGFR) ?120 ml/min and albumin–creatinine ratio (ACR) ?30], and 120 patients were followed up for one year. At one year, they were classified into hyperfiltration (43), normoalbuminuria (29) and microalbuminuria (48) groups. Another 63 T2DM patients without nephropathy were included as controls. Hypertension, patients on angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, eGFR <60 ml/min/1.73 m2 and all proteinuric conditions were excluded. All were subjected to testing for urine protein, ACR, HbA1C, eGFR, along with urinary biomarkers (IL-18, cystatin-C, NGAL and AGT). Comparative analysis of all the diagnostic tests among different subgroups, correlation and logistic regression was done. Results: Urinary IL-18/Cr, cystatin/creatinine (Cr) and AGT/Cr levels were higher in groups of hyperfiltration (13.47, 12.11 and 8.43 mg/g), normoalbuminuria (9.24, 11.74 and 9.15 mg/g) and microalbuminuria (11.59, 14.48 and 10.24 mg/g) than controls (7.38, 8.39 and 1.26 mg/g), but NGAL/Cr was comparable. The area under receiver operating characteristic curve (AUC) and sensitivity of AGT to detect early CKD were higher than ACR and eGFR (0.91 and 90.4%, 0.6 and 40% and 0.6 and 37%, respectively). AUC values of other biomarkers, namely IL-18/Cr, cystatin/Cr and NGAL/Cr, were 0.65, 0.64 and 0.51, respectively. Angio/Cr and IL-18/ Cr showed correlation with log albuminuria (r=0.3, P=0.00, and r=0.28, P=0.00, respectively). NGAL showed correlation with log eGFR (r=0.28 P=0.00). Multivariate logistic analysis showed that odds ratio of developing nephropathy was 7.5 times with higher values of log Angio/Cr. Interpretation & conclusions: Urinary AGT showed a higher diagnostic value than ACR and eGFR followed by IL-18 and cystatin to diagnose DN during pre-albuminuric stages.
ABSTRACT
Objective:To investigate the value of renal artery resistance index (RRI) and urinary angiotensinogen (UAGT) in the early diagnosis of acute kidney injury (AKI) in patients with sepsis.Methods:A prospective study was conducted. Seventy-eight patients with sepsis admitted to the department of critical care medicine of General Hospital of Ningxia Medical University from January to September 2021 were enrolled. Patients were observed for the development of AKI within 1 week. General data [gender, age, body mass index (BMI), major infection sites and critical illness related scores], laboratory indicators [mean arterial pressure (MAP), central venous pressure (CVP), procalcitonin (PCT), arterial blood lactic acid (Lac), etc.], duration of mechanical ventilation and length of intensive care unit (ICU) stay were recorded. After hemodynamic stabilization of the patients, renal ultrasound was performed to measure the RRI within 24 hours after ICU admission. Urine samples were taken immediately after diagnosis, and the level of UAGT was detected by enzyme-linked immunosorbent assay (ELISA). The above parameters were compared between the two groups. Multivariate Logistic regression was used to analyze the risk factors of AKI in patients with sepsis. Receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive value of related indicators for AKI in sepsis.Results:A total of 78 patients were finally enrolled, of which 45 developed AKI and 33 did not. Compared with the non-AKI group, the rates of vasoactive drugs use, 28-day mortality, sequential organ failure assessment (SOFA) score, acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score, PCT, Lac, RRI and UAGT were significantly higher in the AKI group [rates of vasoactive drugs use: 68.9% vs. 39.4%, 28-day mortality: 48.9% vs. 24.2%, SOFA score: 12.0 (10.5, 14.0) vs. 8.0 (7.0, 10.0), APACHEⅡ score: 22.0 (18.0, 27.5) vs. 16.0 (15.0, 18.5), PCT (μg/L): 12.5±2.6 vs. 10.9±2.8, Lac (mmol/L): 2.6 (1.9, 3.4) vs. 1.9 (1.3, 2.6), RRI: 0.74±0.03 vs. 0.72±0.02, UAGT (μg/L): 75.16±19.99 vs. 46.28±20.75, all P < 0.05], the duration of mechanical ventilation and the length of ICU stay were significantly prolonged [duration of mechanical ventilation (days): 8.0 (7.0, 12.0) vs. 5.0 (4.0, 6.0), length of ICU stay (days): 14.0 (10.0, 16.0) vs. 9.0 (8.0, 11.5), both P < 0.01], and MAP was significantly lowered [mmHg (1 mmHg ≈ 0.133 kPa): 68.5±11.2 vs. 74.2±12.8, P < 0.05]. There was no significant difference in other parameters between the two groups. Multivariate Logistic regression analysis showed that SOFA score [odds ratio ( OR) = 2.088, 95% confidence interval (95% CI) was 1.322-3.299], APACHEⅡ score ( OR = 1.447, 95% CI was 1.134-1.845), RRI ( OR = 1.432, 95% CI was 1.103-1.859), and UAGT ( OR = 1.077, 95% CI was 1.035-1.121) were independent risk factors for sepsis complicated with AKI (all P < 0.01). ROC curve analysis showed that SOFA score, APACHEⅡ score, RRI and UAGT had certain predictive value for AKI in septic patients, the area under the ROC curve (AUC) were 0.814 (95% CI was 0.716-0.912), 0.804 (95% CI was 0.708-0.901), 0.789 (95% CI was 0.690-0.888), and 0.840 (95% CI was 0.747-0.934), respectively, and the AUC of RRI combined with UAGT was 0.912 (95% CI was 0.849-0.974), which was better than the above single index (all P < 0.05). Conclusion:RRI combined with UAGT has a high early predictive value for septic AKI.
ABSTRACT
Objective To explore the determination of urinary angiotensinogen (uAGT) in the urine of children with obstructive hydronephrosis and its relationship with impaired renal function, to provide a new and rapid reference index for the preoperative evaluation and postoperative follow-up of the children with hydronephrosis.Methods The data were collected from 48 children who were diagnosed as unilateral congenital renal pelvis and ureter obstruction in the outpatient or inpatient Department of Pediatric Surgery of the First Affiliated Hospital of Zhengzhou University,which were divided into operation group and non-operation group.There were 28 children in operation group(who were all severe hydronephrosis) ,who were all operated with dismembered pyeloplasty.There were 20 children in the non-operation group (who were all mild and moderate hydronephrosis).They temporarily had no surgery signs and hydronephrosis did not become increasingly serious for assuring the regular outpatient follow-up after being diagnosed as hydronephrosis;there were 20 children in the control group, 10 of which were male, and 10 female.The males were hospitalized children with hydrocele and the females were with inguinal hernia.Gender composition among the 3 groups, and the average age difference was not statistically significant.The clean urina of children in 3 groups was collected,3 times for operation group, once before operation and once in 6 weeks and once in 12 weeks after operation;3 times for non-operation group and control group with interval of 6 weeks in outpatient clinic.The children in operation group and non-operation group were all scanned for glomerular filtration rate (GFR) of diseased renal with radionuclide;enzyme-linked immunosorbent assay (ELISA) was adopted to determine the content of uAGT in the urine of the 3 groups of children, and automatic biochemical analyzer was used to measure the amount of urine creatinine (uCr).Results Before operation, in 6 weeks and 12 weeks after operation, uAGT / uCr average water of non-operation group and control group was significantly lower than the operation group, all the differences were statistically significant (F =34.360,14.683,5.035, all P ＜ 0.05).Preoperative and postoperative uAGT / uCr and GFR of diseased renal were of negative correlation(r =-0.647,-0.786, all P ＜ 0.05).In operation group, the preoperative and postoperative GFR average of diseased renal was 37.18 ± 7.31 and 45.27 ± 8.18.The difference of GFR changes was statistically significant before and after treatment (t =-3.971, P =0.000).Conclusions uAGT/uCr increased evidently in congenital renal pelvis and ureter obstruction patients who needed operation, so increase of uAGT might be the indicator of impaired renal function caused by obstructive hydronephrosis of children.