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.

The problem of pulmonary arterial hypertension in end-stage renal disease: can peritoneal dialysis be the solution.

BACKGROUND: Pulmonary arterial hypertension (PAH) in the setting of end-stage renal disease (ESRD) has important prognostic and therapeutic consequences. We estimated the prevalence of PAH among patients with ESRD treated with automated peritoneal dialysis (APD), investigated the effect of different variables and compared pulmonary artery pressure and cardiac function at the beginning and end of the study. METHODS: This is a 5-year study in which 31 ESRD patients on APD were recruited after fulfilling inclusion criteria. Blood samples were collected from all patients for the biochemical and hematological data at the beginning of the study and every month and at the study termination. Total body water (TBW) and extracellular water (ECW) were calculated using Watson's and Bird's calculation methods. All patients were followed-up at 3-month interval for cardiac evaluation. Logistic regression analysis was used to assess the relation between different variables and PAH. RESULTS: The mean age of the study population (n = 31) was 51.23 ± 15.24 years. PAH was found in 24.2% of the patients. Mean systolic pulmonary artery pressure (sPAP) and mean pulmonary artery pressure (mPAP) were significantly higher in the APD patients at study initiation than at the end of the study (40.75 + 10.61 vs 23.55 + 9.20 and 29.66 + 11.35 vs 18.24 + 6.75 mmHg respectively, p = 0.001). The median ejection fraction was significantly lower in patients with PAH at zero point than at study termination [31% (27-34) vs 50% (46-52), p = 0.002]. Hypervolemia decreased significantly at the end of study (p <  0.001) and correlated positively with the PAP (r = 0.371 and r = 0.369), p = 0.002). sPAP correlated with left ventricular mass index, hemoglobin level, and duration on APD. CONCLUSIONS: Long term APD (> 1 years) seemed to decrease pulmonary arterial pressure, right atrial pressure and improve left ventricular ejection fraction (LVEF). Risk factors for PAH in ESRD were hypervolemia, abnormal ECHO findings and low hemoglobin levels. Clinical and echocardiographic abnormalities and complications are not uncommon among ESRD patients with PAH. Identification of those patients on transthoracic echocardiography may warrant further attention to treatment with APD.

Successfully treating three patients with acute kidney injury secondary to COVID-19 by peritoneal dialysis: Case report and literature review.

Coronavirus Disease 2019 (COVID-19) is a pandemic disease that increased the burden on health-care system. In the Kingdom of Saudi Arabia, 74,795 cases have been reported until 26 May 2020 and the number of cases is rapidly increasing. The mortality rate of COVID-19 worldwide is 6.37%. Here we report three cases of acute kidney injury (AKI) secondary to pneumonia of severe COVID-19; they were treated with automated peritoneal dialysis (PD) with full recovery. To the best of our knowledge, few reports in the literature have discussed the use of PD in AKI secondary to COVID-19.

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.

Potential serum biomarkers for early detection of diabetic nephropathy.

AIM: Diabetic nephropathy (DN) is considered as one of the diabetic complications affecting up to 40% of patients with type 1 or type 2 diabetes. In clinical practice, the frequently used markers of renal disease and progression are serum creatinine, estimated glomerular filtration rate (eGFR) and albuminuria. The aim of this study is to determine new biomarkers in human serum which are promising for early detection of DN. METHODS: This study included 50 patients with type 2 diabetes mellitus (T2DM) and 25 clinically healthy individuals. The patients were divided into two groups; group I included 25 T2DM patients with normoalbuminuria, and group II consisted of 25 T2DM patients with microalbuminuria. In all groups, neutrophil gelatinase-associated lipocalin (NGAL), ß-trace protein (ßTP) and microRNA- 130b (miR-130b) were estimated. RESULTS: The serum levels of NGAL and ßTP were significantly elevated in T2DM patients with microalbuminuria (group II) compared with T2DM patients with normoalbuminuria (group I) and control subjects but there was no significant difference between group I and control subjects. Serum miR-130b level was significantly decreased in patients with T2DM (groups I and II) compared with healthy control subjects, with a higher decrease in their levels in group II compared with group I. CONCLUSION: Our results suggest that serum NGAL and ßTP as tubular and glomerular markers respectively, together with serum miR-130b may be independent and reliable biomarkers for early detection of DN in patients with T2DM.