Cell cycle arrest biomarkers for the early detection of acute allograft dysfunction and acute rejection in living donor kidney transplantation: a cross-sectional study from Egypt.

Background: Urinary tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) are G1 cell arrest biomarkers that have demonstrated accuracy and validity in predicting and diagnosing acute kidney injury (AKI). This study aimed to evaluate the validity of [TIMP-2]×[IGFBP7] in diagnosing acute allograft dysfunction and its utility in distinguishing acute rejection (AR) from nonrejection causes in kidney transplantation. Methods: This study included 48 adult living donor kidney transplant recipients (KTRs; 18 with AR, 15 with nonrejection causes of AKI, and 15 with stable grafts). Urinary TIMP-2 and IGFBP7 were measured, and [TIMP-2]×[IGFBP7] was calculated in all subjects. Results: IGFBP7, TIMP-2, and [TIMP-2]×[IGFBP7] were statistically significantly higher in KTRs with acute allograft dysfunction than in those with stable grafts. [TIMP-2]×[IGFBP7] was statistically significantly higher in KTRs with AR than in those with nonrejection AKI. [TIMP-2]×[IGFBP7] at a cutoff level of 0.278 (ng/mL)2/1,000 had an area under the curve (AUC) of 0.99 with a sensitivity of 100% and a specificity of 93.3% in diagnosing acute allograft dysfunction, while at a cutoff level of 0.803 (ng/mL)2/1,000 had an AUC of 0.939 with a sensitivity of 94.4% and a specificity of 83.3% in diagnosing AR. Conclusions: Besides its role in the early detection of acute allograft dysfunction, [TIMP-2]×[IGFBP7] may help to differentiate between AR and nonrejection causes in KTRs. However, whether and how urinary [TIMP-2]×[IGFBP7] can be used in clinical diagnosis still requires further research.

Urinary podocalyxin: Is it a real index of disease activity in egyptian patients lupus nephritis?

Systemic lupus erythematosus (SLE) is an inflammatory autoimmune disease characterized by production of a number of antinuclear antibodies. Podocyte injury is an important feature and can be detected by several markers including podocalyxin. We aimed to evaluate the impact of SLE on urinary levels of podocalyxin and to determine its relationship to renal biopsy, proteinuria, and disease activity in lupus nephritis (LN) patients. Sixty individuals were recruited; 30 SLE patients with LN as well as 30 healthy volunteers and they were subjected to full history, clinical examination, kidney function, protein/creatinine ratio, urinary podocalyxin, and kidney biopsy. Patients with LN had higher level of urinary podocalyxin (3.96 ± 2.24) than the other group (0 ± 0), (P <0.001). Class IV LN was the most common class found among LN patients [18 cases (60%)]. There was a statistically significant positive correlation between SLE disease activity index score, protein/creatinine ratio, and urinary podocalyxin (P <0.001, r = 0.98) (P <0.001, r = 0.765). There was a statistically significant negative correlation between serum albumin, serum calcium, and urinary podocalyxin (P = 0.001, r = -0.589) (P = 0.025, r = -0.407). Urinary podocalyxin level significantly predicts the pathological impact of SLE on the kidney and could be used as a noninvasive marker for such effect and its progression.

Calcification of abdominal aorta in patients recently starting hemodialysis: A single-center experience from Egypt.

Vascular calcification (VC) is a well-known complication in patients with chronic kidney disease (CKD). Keeping in mind, the end goal to assess the genuine effect of mineral bone disease in the pathogenesis of blood vessel calcification during the pre-dialysis course of CKD, we assessed the prevalence and extent of abdominal aortic calcification (AAC) in nondiabetic CKD patients recently starting hemodialysis (HD). Eighty-one patients with end-stage renal disease beginning HD over a one-month period were selected. They underwent a detailed clinical examination and laboratory evaluation, including serum calcium, phosphorus, parathyroid hormone, fibroblast growth factor (FGF-23), and alkaline phosphatase were measured, and spiral computed tomography was performed to evaluate AAC score. AAC was present in 64 patients (79%). There was a significant correlation between the AAC score and age (r = 0.609, P <0.001) and FGF-23 (r = 0.800, P <0.001). This study suggests that the prevalence and extent of AAC are critical in incident HD patients. Serum FGF-23 level is the sole statistically significant correlate of AAC in these patients.

Fibroblast growth factor-23 as a predictor biomarker of acute kidney injury after cardiac surgery.

Renal ischemia/reperfusion injury is a major cause of acute kidney injury (AKI). The lack of early biomarkers for predicting AKI has hampered our ability to initiate preventive and therapeutic measures in an opportune way. Fibroblast growth factor 23 (FGF-23) is elevated in chronic kidney disease, but data on FGF-23 in humans with AKI are limited. Herein, we tested whether FGF-23 levels rise early in the course of AKI following cardiac surgery. We prospectively evaluated eighty adult patients who underwent cardiac surgery. Patients were divided into two groups (AKI and non-AKI group) on the basis of whether they developed postoperative AKI within 24 h after surgery. Plasma FGF-23 levels were measured before surgery and 24 h after surgery. The primary outcome was AKI diagnosed using the AKI Network criteria. Forty-five patients (56.2.5%) developed AKI after surgery. Plasma FGF-23 increased significantly from a mean of 26.8 ± 2.47 ng/mL at baseline to 341.7 ± 38.1 ng/mL 24 h after cardiopulmonary bypass. Univariate analysis showed a significant correlation between AKI and the following: percent change in plasma FGF-23, postoperative serum level of creatinine, FGF-23, and neutrophil gelatinase-associated lipocalin. Receiver operating characteristic curve analysis revealed that, for percent change in plasma FGF-23 concentrations at 24 h, the area under the curve was 0.9, sensitivity was 100%, and specificity was 97.1%. Plasma FGF-23 percent change is more valid compared with FGF-23 before or after procedure in the prediction of AKI and represents a novel and highly predictive early biomarker for AKI after cardiac surgery.