Association between renal function parameters, clinical severity score and mortality risk among adult Sudanese sickle anemia patients.

BACKGROUND: Sickle Cell Anemia (SCA) is an autosomal recessive haemoglobinopathy with high morbidity and mortality. Global survival of sickle patients is increased due to advances in management; and subsequently, prevalence of chronic complications including renal manifestations also increased. Therefore, early detection and management of these complications is mandatory. This study aimed to investigate the estimated Glomerular Filtration Rate (eGFR), proteinuria and serum uric acid as markers of renal involvement in Sudanese sickle adults and association between these parameters and clinical severity score of sickle cell disease. METHODS: Cross-sectional hospital-based study included thirty-two adult Sudanese patients diagnosed with SCA and twenty-three as controls. Written informed consent was obtained from each participant. Blood and urine samples were collected. Severity score was calculated using Bios online calculator and eGFR was calculated using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula without adjustment for ethnicity. Associations between the severity score and renal parameters were tested using unpaired T test and Mann Whitney test for normally and non-normally distributed data and correlations between variables were tested using SPSS version 23. RESULTS: Protein/Creatinine Ratio (PCR) was significantly higher (p-value < 0.001) in sickle cell anaemia group compared to controls. Hyper-filtration and Hyperuricemia were manifested in 75% and 6.3% of SCA group respectively. There was no association between the severity score and renal manifestations in the SCA group. CONCLUSIONS: Hyper-filtration and proteinuria were the most prevalent renal manifestations in SCA group. Further studies are recommended to determine the predictors of renal complications and ensure early management of such complications.

Xiao-Shen-Formula, a Traditional Chinese Medicine, Improves Glomerular Hyper-Filtration in Diabetic Nephropathy via Inhibiting Arginase Activation and Heparanase Expression.

Hyperglycemia induces glomerular hyper-filtration, which contributes to the development of diabetic nephropathy (DN), a condition that remains a challenge for treatment. The present study investigated the effect of Xiao-Shen-Formula (XSF) used for treatment of renal injury in type 1 DN mice model induced by streptozotocin (STZ) and its underlying mechanism in cultured human glomerular endothelial cell (hGECs). Studies were performed using control, diabetic DN, DN treated with XSF groups (1 g/kg/d, LXSF or 3 g/kg/d, HXSF) for 6 weeks and hGECs were post-treated with mice serum containing HXSF (MS-HXSF) and arginase inhibitor (ABH, 100 µM) in high glucose medium. HXSF treatment restored STZ-induced renal hyper-filtration, glomerulosclerosis, renal microvascular remodeling and the increased levels of systemic reactive oxidative species and inflammatory cytokines, accompanied by preventing the decreased expression of glomerular heparin sulfate and the increased levels of cortical heparanase and argianse2 protein and arginase activity. In hGECs study, MS-HXSF ameliorated the enhancement in arginase activity, the protein/mRNA expression of heparanase, mRNA levels of vascular cell adhesion molecule-1, intercellular adhesion molecule-1, monocyte chemoattractant protein-1 and permeability of hGECs monolayers as well as the depression of nitric oxide production. Besides all these protective effects, XSF blunted the mRNA expression of TNF-α in vivo and vitro studies as well, which was not changed by the post-treatment of ABH or HXSF plus ABH. This study demonstrated that the protective effect of XSF might be related with vascular prevention, anti-inflammation and anti-oxidation through intervening multi-targets including glomerular endothelial arginase-heparanase signaling pathway in DN model.

Determinants associated with the correction of glomerular hyper-filtration one year after bariatric surgery.

BACKGROUND: Increased adipokine production and hyperfiltration may explain the links between obesity and chronic kidney disease. Indeed, hyperfiltration may precede a subsequent accelerated decline of kidney function in these patients. Glomerular filtration rate decreases after bariatric surgery in young obese patients with hyperfiltration. OBJECTIVE: Our aim was to identify the factors associated with this decrease 1 year after bariatric surgery. SETTING: We used data from a prospective cohort of severely obese patients who underwent bariatric surgery in Nice University Hospital. METHODS: We analyzed 175 patients before and 1 year after bariatric surgery. Low-grade inflammation was evaluated by serum C-reactive protein levels. Lean body mass and fat body mass were estimated by bioelectric impedance analysis. Body surface area was assessed by the Du Bois formula. Serum creatinine levels were used to estimate glomerular filtration rate by the chronic kidney disease-epidemiology collaboration (CKD-EPI) equation. Glomerular filtration rate was de-adjusted from standard body surface area and then divided by lean body mass to calculate the decrease in hyperfiltration and to separate the patients into 2 groups: above or below the median decrease of hyperfiltration after bariatric surgery. RESULTS: The factors associated with a large correction of hyperfiltration were baseline C-reactive protein levels (10.0 ± 5.8 mg/L versus 12.7 ± 7.4 mg/L, P = .01) and brachial circumference (41 ± 4 cm versus 44 ± 5 cm, P = .006). A high fat mass reduction rate was significantly associated with a substantial hyperfiltration reduction after bariatric surgery (P<.001) independently of sex and surgical procedure. CONCLUSIONS: The correction of hyperfiltration is associated with a high reduction rate of fat mass after bariatric surgery but may be limited by low-grade inflammation.

Effects of protein kinase-induced cytoplasmic calcium changes in mesangial cells on glomerular hy- perfiltration in early stage of rat diabetes mellitus / 中国糖尿病杂志

Objective To elucidate functional alterations of glomerular mesangial cell (GMC) contraction and its relationship with diabetic glomerular hyperfiltration. Methods Male Wistar rats were divided into groups of normal control and 2 weeks diabetes induced by STZ. GMC were cultured in the presence of normal glucose (5mM). Meanwhile in comparison GMC obstained from normal rats were cultured in the presence of 30 mM glucose for 48 h in vitro. By using laser scanning confocal microscopy (LSCM) , we measured basal calcium concentration, the changes of calcium level in response to vasoconstrictor agonist angiotensin H (Ang I ),and the effect of protein kinase C (PKC) inhibitor PMAC10 M,24 h)on cytosol calcium of GMCs. Results The creatinine clearance rate (Ccr) was increased with age in diabetic rats, reaching a peak at 2 weeks (P