Erythrocyte glutathione transferase: a potential new biomarker in chronic kidney diseases which correlates with plasma homocysteine.

The erythrocyte glutathione S-transferase (e-GST) is a member of a superfamily of inducible enzymes involved in cell detoxification that shows an increased expression in chronic kidney disease (CKD) patients. We propose a new automated analysis procedure for e-GST activity that has been validated in 72 CKD patients and 62 maintenance hemodialysis patients (MHD). Regression analysis was carried out to assess association between e-GST activity data, main clinical variables, and plasma homocysteine (Hcy), a modified sulfur amino acid known as potential risk factor for cardiovascular disease that is increased above normal levels in more than 90% of the uremic patients. An increased e-GST activity was confirmed in MHD patients (N=62; 10.2±0.4 U/gHb) compared with healthy subjects (N=80; 5.8±0.4 U/gHb), and as an original finding, a significant increase of e-GST activity was observed in pre-dialysis CKD patients with a positive correlation with disease severity weighted according to the four stages of "Kidney Disease Outcomes Quality Initiative" classification (7.4±0.5, 8±1, 9.5±0.6, 12±1 U/gHb, respectively). No correlation was found between e-GST activity and hemoglobin, transferrin, blood iron and the markers of systemic inflammation and renal function such as alpha-1 acid glycoprotein and high-sensitive C-Reactive Protein, beta-2 microglobulin and the index of malnutrition-inflammation PINI, while a significant correlation was observed for the first time between plasma Hcy and e-GST activity (r2=0.64, P<0.0001) in MHD patients. Hcy, however, was not identified as an inhibitor of e-GST enzyme. The results in this study suggest the potential for automated e-GST analysis as a valuable tool to further explore phase II-related uremic toxicity in CKD and MHD patients.

Renal Parenchymal Thickness in Patients with Systemic Sclerosis Is Related to Intrarenal Hemodynamic Variables and Raynaud Renal Phenomenon.

OBJECTIVE: Renal involvement in systemic sclerosis (SSc) ranges from urinary abnormalities, reduction of glomerular filtration rate, and high renal resistive index, to scleroderma renal crisis. Intrarenal resistance indices are considered markers of renal SSc-associated vasculopathy. The aim of this study is to evaluate renal morphological variables, such as renal length, parenchymal thickness, atrophy index, and renal sinus in patients with SSc and to correlate it with renal function and hemodynamic variables. METHODS: There were 92 patients with SSc and 40 healthy controls (HC) enrolled in this study. Doppler and renal ultrasound (US) including renal length, parenchymal thickness, atrophy index, renal sinus, and intrarenal resistive index were measured in patients with SSc and HC. RESULTS: Renal US showed significant differences between HC and patients with SSc. The renal length (mm; 106.7 ± 5.1 vs 102.3 ± 8.4) and renal sinus (70.7 ± 7.9 vs 65.3 ± 7.7 mm) were significantly (p = 0.001) higher in HC than patients with SSc. The parenchymal thickness was significantly (p = 0.004) higher in HC than patients with SSc (18 ± 3.1 vs 16.3 ± 2.5 mm). Pulsatility index, resistive index, and systolic/diastolic ratio were significantly (p < 0.0001) lower in HC than patients with SSc. The renal length was significantly (p = 0.004) higher in diffuse cutaneous SSc (105 ± 8.4) than in limited cutaneous SSc (99.5 ± 7.5). CONCLUSION: In SSc, kidney involvement is subclinical and is related to vascular injury, Raynaud phenomenon, and chronic hypoxia that can modify renal morphology. Serum creatinine is a poor marker of renal damage, and renal US could be a useful tool - together with Doppler - to evaluate renal involvement in a systemic and chronic disease such as SSc.

Hemodialysis biomarkers: total advanced glycation end products (AGEs) against oxidized human serum albumin (HSAox).

AIMS: Nephropathic patients show higher levels of advanced glycation end products (AGEs) and oxidized human serum albumin (HSAox) compared to healthy subjects. These two classes of compounds are formed as the result of oxidative insults; for this reason, they can be useful oxidative stress biomarkers. The present study examines the variation of AGEs and HSAox in hemodialysis (HD) patients before and after dialysis session, evaluating the impact of different dialytic techniques and filters on their removal. METHODS: A total of 50 healthy subjects (control group) and 130 HD patients were enrolled in the study. Hemodialysis patients were subdivided based on dialytic techniques: 109 in diffusive technique and 22 in convective technique. We monitored HSAox, AGEs and other laboratory parameters at early morning in healthy subjects and in HD patients before and after the dialysis procedures. RESULTS: The level of HSAox decreases after a single dialytic session (from 58.5 ± 8.8% to 41.5 ± 11.1%), but the concentration of total AGEs increases regardless of adopted dialytic techniques (from 6.8 ± 5.2 µg/ml to 9.2 ± 4.4 µg/ml). In our study, levels of HSAox and total AGEs are similar in diabetic and non-diabetic HD patients. The increase in total AGEs after dialysis was only observed using polysulfone filters but was absent with polymethacrylate filters. CONCLUSIONS: HSAox is a simple and immediate method to verify the beneficial effect of a single dialysis session on the redox imbalance, always present in HD patients. Total AGEs assayed by ELISA procedure seem to be a less reliable biomarker in this population.