Urinary 20-HETE: A prospective Non-Invasive prognostic and diagnostic marker for diabetic kidney disease.

INTRODUCTION: The identification and validation of a non-invasive prognostic marker for early detection of diabetic kidney disease (DKD) can lead to substantial improvement in therapeutic decision-making. OBJECTIVES: The main objective of this study is to assess the potential role of the arachidonic acid (AA) metabolite 20-hydroxyeicosatetraenoic (20-HETE) in predicting the incidence and progression of DKD. METHODS: Healthy patients and patients with diabetes were recruited from the Hamad General Hospital in Qatar, and urinary 20-HETE levels were measured. Data analysis was done using the Statistical Package for Social Sciences (SPSS). RESULTS: Our results show that urinary 20-HETE-to-creatinine (20-HETE/Cr) ratios were significantly elevated in patients with DKD when compared to patients with diabetes who did not exhibit clinical signs of kidney injury (p < 0.001). This correlation was preserved in the multivariate linear regression accounting for age, diabetes, family history of kidney disease, hypertension, dyslipidemia, stroke and metabolic syndrome. Urinary 20-HETE/Cr ratios were also positively correlated with the severity of kidney injury as indicated by albuminuria levels (p < 0.001). A urinary 20-HETE/Cr ratio of 4.6 pmol/mg discriminated between the presence and absence of kidney disease with a sensitivity of 82.2 % and a specificity of 67.1%. More importantly, a 10-unit increase in urinary 20-HETE/Cr ratio was tied to a 10-fold increase in the risk of developing DKD, suggesting a 20-HETE prognostic efficiency. CONCLUSION: Taken together, our results suggest that urinary 20-HETE levels can potentially be used as non-invasive diagnostic and prognostic markers for DKD.

mTORC2 Signaling Regulates Nox4-Induced Podocyte Depletion in Diabetes.

AIM: Podocyte apoptosis is a critical mechanism for excessive loss of urinary albumin that eventuates in kidney fibrosis. Oxidative stress plays a critical role in hyperglycemia-induced glomerular injury. We explored the hypothesis that mammalian target of rapamycin complex 2 (mTORC2) mediates podocyte injury in diabetes. RESULTS: High glucose (HG)-induced podocyte injury reflected by alterations in the slit diaphragm protein podocin and podocyte depletion/apoptosis. This was paralleled by activation of the Rictor/mTORC2/Akt pathway. HG also increased the levels of Nox4 and NADPH oxidase activity. Inhibition of mTORC2 using small interfering RNA (siRNA)-targeting Rictor in vitro decreased HG-induced Nox1 and Nox4, NADPH oxidase activity, restored podocin levels, and reduced podocyte depletion/apoptosis. Inhibition of mTORC2 had no effect on mammalian target of rapamycin complex 1 (mTORC1) activation, described by our group to be increased in diabetes, suggesting that the mTORC2 activation by HG could mediate podocyte injury independently of mTORC1. In isolated glomeruli of OVE26 mice, there was a similar activation of the Rictor/mTORC2/Akt signaling pathway with increase in Nox4 and NADPH oxidase activity. Inhibition of mTORC2 using antisense oligonucleotides targeting Rictor restored podocin levels, reduced podocyte depletion/apoptosis, and attenuated glomerular injury and albuminuria. INNOVATION: Our data provide evidence for a novel function of mTORC2 in NADPH oxidase-derived reactive oxygen species generation and podocyte apoptosis that contributes to urinary albumin excretion in type 1 diabetes. CONCLUSION: mTORC2 and/or NADPH oxidase inhibition may represent a therapeutic modality for diabetic kidney disease. Antioxid. Redox Signal. 25, 703-719.

Standard continuous ambulatory peritoneal dialysis therapy provides similar initial T-Kt/V regardless of the patient's peritoneal membrane transporter category: Single-center experience.

Patients on continuous ambulatory peritoneal dialysis (CAPD) are routinely evaluated using the peritoneal equilibrium test (PET) to determine the best method for achieving target total dialysis clearance (T-Kt/V). In this study, we tested the hypothesis that standard CAPD prescription would achieve an initial T-Kt/V of more than 1.7 in all the patients regardless of their PET measurements. This is a retrospective study that included patients who started standard CAPD of four two-liter exchanges per day. The study included 118 patients; their mean age was 51.5 years with a standard deviation (SD) of 14.39 years. There were 83 males (70.3%) and 35 females (29.7%). PET and Kt/V were performed during the first four to six weeks of the study. The PET classified the patients into four categories: 24 (20.3%), high transporters; 65 (55.1%), high average; 28 (23.7%), low average; and one (0.8%), low transporter. Patients were then divided in two groups: Group 1 comprised of the high transporters while Group 2 included all the other patients. The T-Kt/V of the two groups was similar; in Group 1, it was 2.57 (± 1.17) and in Group 2 it was 2.50 (± 0.88) (P = 0.77). The T-Kt/V of patients with no residual renal function was also similar; in Group 1 and Group 2 it was 1.8 (± 0.29) and 1.97 (± 0.56), respectively (P = 0.45). All patients in our study who started on standard CAPD treatment had an adequate initial T-Kt/V. Thus, our data demonstrate that all patients with end-stage renal disease can safely begin standard CAPD without PET, which only needs to be performed if the patient encounters trouble in his/her T-Kt/V or fluid removal.

Fine needle aspiration cytopathology of pediatric lymphadenopathy among Sudanese children.

BACKGROUND: Pediatric lymphadenopathy is a challenging medical situation for the child patient, the parents, and the physician. Although the bulk of masses will be benign the fear of malignancy is omnipresent. Therefore, the objective of this study was to identify the common cytopathological patterns of lymphadenopathy among Sudanese children. METHODS: One hundred pediatric patients presenting with peripheral lymphadenopathy were included in the study, their ages ranging from 2 to 14 years, with a mean age of 7 years. Demographic characteristics, clinical manifestations and FNA materials were prospectively obtained. RESULTS: FNA was performed in 100 cases (100%). There were no technical complications. All cases confirmed adequacy of specimen. Overall, FNA demonstrated 90 (90%) benign lesions and 10 (10%) malignant diagnosis. The benign lesions were reactive lymphoid hyperplasia (n=64), followed by benign granulomatous disease (n=26). Of the 10 cases diagnosed with malignancy, 7 (7%) were cases of non-Hodgkin`s lymphoma and the remaining 3 (3%) were Hodgkin's lymphomas. CONCLUSION: Pediatric lymphadenopathy is common in Sudan. CLA is the common frequent site. Lymphoma represents a major challenge in this setting.

20-HETE and EETs in diabetic nephropathy: a novel mechanistic pathway.

Diabetic nephropathy (DN), a major complication of diabetes, is characterized by hypertrophy, extracellular matrix accumulation, fibrosis and proteinuria leading to loss of renal function. Hypertrophy is a major factor inducing proximal tubular epithelial cells injury. However, the mechanisms leading to tubular injury is not well defined. In our study, we show that exposure of rats proximal tubular epithelial cells to high glucose (HG) resulted in increased extracellular matrix accumulation and hypertrophy. HG treatment increased ROS production and was associated with alteration in CYPs 4A and 2C11 expression concomitant with alteration in 20-HETE and EETs formation. HG-induced tubular injury were blocked by HET0016, an inhibitor of CYPs 4A. In contrast, inhibition of EETs promoted the effects of HG on cultured proximal tubular cells. Our results also show that alteration in CYPs 4A and 2C expression and 20HETE and EETs formation regulates the activation of the mTOR/p70S6Kinase pathway, known to play a major role in the development of DN. In conclusion, we show that hyperglycemia in diabetes has a significant effect on the expression of Arachidonic Acid (AA)-metabolizing CYPs, manifested by increased AA metabolism, and might thus alter kidney function through alteration of type and amount of AA metabolites.

Expression of EGFR and p53 in head and neck tumors among Sudanese patients.

BACKGROUND: The aim of this study was to assess EGFR and p53 expression in head and neck tumors among Sudanese patients using immunohistochemistry. MATERIALS AND METHODS: A retrospective descriptive study was performed on 150 samples from patients diagnosed with HNCs as well as 50 from individuals with benign head and neck tumors. EGFR and p53 expression was assessed using immunohistochemistry (IHC). RESULTS: EGFR was expressed in 126/150 (84%) of HNCS and 6/50 (12%) benign head and neck tumors where as p53 was expressed in 29/150 (19.3%) of HNCs and 2/50 (4%) of benign head and neck tumors, with significance at p values of 0.001 and 0.009 respectively. CONCLUSIONS: There is a significant association between EGFR, P53 expression and head and neck cancers among Sudanese patients.

Microalbuminuria in hepatitis C-genotype 4: effect of pegylated interferon and ribavirin.

AIM: To study the relation between hepatitis C virus (HCV) genotype 4 and microalbuminuria and renal impairment in relation to hepatic histology, and viremia in the absence of cryoglobulinemia, and to examine the effect of treatment on microalbuminuria. METHODS: Three hundred subjects, including 233 HCV genotype-4 infected patients, were tested for cryoglobulinemia, microalbuminuria, albumin creatinine ratio (ACR), urea, creatinine, and estimated glomerular filtration rate (eGFR). The parameters were measured again in the HCV patients after 48 wk of treatment with pegylated interferon and ribavirin. RESULTS: Significantly higher levels of microalbuminuria were detected in HCV-positive patients compared to HCV-negative controls (median 9.5 vs 5.9, respectively, Kruskal-Wallis P = 0.017). Log microalbuminuria was significantly correlated with hepatic inflammation (r = 0.13, P = 0.036) and fibrosis (r = 0.12, P = 0.061), but not with viral load (r = -0.03, P = 0.610), or alanine transaminase (r = -0.03, P = 0.617). Diabetes mellitus neither significantly moderated (chi(2) = 0.13, P = 0.720), nor mediated (Sobel test P = 0.49) the HCV effect. HCV status was significantly associated with log microalbuminuria (chi(2) = 4.97, P = 0.026), adjusting for age, gender, diabetes, cryoglobulinemia, urea and creatinine. A positive HCV status was not significantly associated with low eGFR (< 60 mL/min every 1.73 m(2)) [odds ratio (OR): 0.5, 95% confidence interval (CI): 0.2-1.4], nor with high ACR (OR: 1.7, 95% CI: 0.7-4.1). End-of-treatment response (ETR) was achieved in 51.9% of patients. Individuals with ETR had significantly lower microalbuminuria post-treatment (chi(2) = 8.19, P = 0.004). CONCLUSION: HCV affected the development of microalbuminuria independent of diabetes or cryoglobulinemia. Combination therapy of pegylated interferon-ribavirin had a positive effect in reducing microalbuminuria.