Iranian Journal of Kidney Diseases
Volume:13 Issue: 2, Mar 2019

Mitochondrial dysfunction, apoptosis and oxidative stress, are the interrelated events underlining the pathology of numerous diseases including cardiovascular, neurologic, and metabolic disorders. Due to playing a critical role in glucose and fatty acids' metabolism, L-carnitine probably has the potential to adjust these unfavorable events. The present review has evolved based on existing literature that investigated the mechanisms of L-carnitine and its derivatives based mitochondrial dysfunction, oxidative stress, and apoptosis related modulation. The released studies have been searched with the databases including Google Scholar, Scopus, and PubMed out of which overall 76 full-length articles have been chosen and recruited in this review. L-carnitine exerts protective effects against these cellular events in several manners including the maintenance of mitochondrial functions and decreasing the production of reactive oxygen species at different points. In clinical setting, these effects could be applied to treat a variety of associated diseases.

Diabetic nephropathy (DN) is a serious complication of diabetes mellitus involving damage to the capillaries in the glomerulus. This study aimed to explore key genes and signaling pathways participate in the progression of DN. Two gene expression profile datasets GSE1009 and GSE30528 downloaded from Gene Expression Omnibus (GEO) were used to analyze the differentially expressed genes (DEGs) between DN samples and controls. Coupled two-way clustering (CTWC) and correspondence analysis were performed to explore the potential functions of DEGs. Then, Gene Ontology (GO) terms and pathways associated with DEGs were identified, followed by constructing of the co-expressed gene network and module. Ultimately, the regulatory network based on the DEGs, miRNAs and transcription factors (TFs) was established. Total 283 common DEGs were identified from the two datasets, including 219 down-regulated ones (bone morphogenetic protein 7 (BMP7), decay accelerating factor (CD55) and coagulation Factor V (F5) etc.) and 64 up-regulated ones (inhibin beta c subunit (INHBC) and colony stimulating factor 1 receptor (CSF1R) etc.). The miRNA-TF regulatory network was established with three miRNAs, 8 TFs and 58 DEGs. Besides, three significant pathways including cytokine-cytokine receptor interaction, complement and coagulation cascades and TGF-beta signaling pathways were identified. BMP7, CD55, CSF1R, INHBC and F5 are likely to take crucial roles in the pathogenesis of DN.

Chronic kidney disease (CKD) promotes hypertrophy and fibrosis in heart, and increases the risk of cardiovascular mortality. Ferric citrate is a dietary phosphate binder used to control hyperphosphatemia in CKD patients. It has been shown to raise iron stores, improve anemia and secondary hyperparathyroidism, and decrease vascular calcification in CKD patients. The present study was done to explore the effects and mechanism of actions of ferric citrate on cardiac hypertrophy and fibrosis. Male SD rats were randomized to CKD (5/6 nephrectomized) and sham-operated control groups. CKD rats were fed regular diet or a diet containing 4% ferric citrate. After 8 weeks, hemoglobin, renal function and cardiovascular endpoints including blood pressure, heart/body weight ratio, serum N-terminal prohormone of brain natriuretic peptide (NT-proBNP), cardiac histology and markers of hypertrophy, fibrosis and inflammation were assessed. Compared to the controls, untreated CKD group exhibited hypertension, elevated serum urea, creatinine, phosphate, and NT-proBNP concentrations, anemia, cardiomegaly ,cardiac hypertrophy and fibrosis. Treatment with ferric citrate significantly increased hemoglobin and serum iron concentrations, reduced serum phosphate and NT-proBNP levels and ameliorated hypertension, heart/body weight ratio, cardiac hypertrophy, fibrosis and inflammation. In addition, ferric citrate administration reduced the size of cardiomyocytes and expressions of myocardin, transforming growth factor-β, interleukin-6 and monocyte chemotactic protein 1. Treatment with ferric citrate attenuated renal failure and cardiovascular abnormalities including myocardial hypertrophy and fibrosis in CKD rats.

The patients with non-dipper hypertension have an increased risk for target organ damage because of inflammation and platelet activation. In this study, we aimed to investigate the association between ambulatory blood pressure monitoring (ABPM) values and inflammation with platelet indices in children with dipper and non-dipper hypertension. A total of 153 patients who underwent ABPM were included in this retrospective study. The participants were divided into three groups (61 non-dipper hypertensive, 28 dipper hypertensive, 64 normotensive). Neutrophil and platelet count, neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), mean platelet volume (MPV), plateletcrit (PCT), and platelet distribution width (PDW) were matched data among groups. The neutrophil counts were higher in the non-dipper and dipper groups compared with the normotensive group (P < .05, P < .05, respectively). Also, MPV levels were significantly higher in the non-dipper and dipper groups than in normotensive group (P < .05, P < .05, respectively). Logistic regression analysis showed significant association between non-dipper status and MPV with platelet count (P < .05, P < .05, respectively). The abilities of MPV and platelet count to predict the non-dipper status were determined by receiver operating characteristic curve analysis (areas under the curve were 0.709 and 0.604, respectively). The higher MPV and neutrophil count may be potential indicators of increased risk for the development of hypertension in children. In addition, MPV and platelet count may help to determine the presence of non-dipper status in children with hypertension.

Hepcidin is a key regulator of iron homeostasis, takes part in pathophysiology of anemia and cardiovascular disease in maintenance hemodialysis (MHD) patients. The aim of this study was to compare the effect of glucose-free and glucose-containing dialysate on the clearance of hepcidin-25 during a hemodialysis (HD) session and discuss its potential mechanism in MHD patients. In a longitudinal interventional study of 30 stable MHD patients without diabetes, we measured serum hepcidin-25 and plasma catecholamines (adrenaline, noradrenaline, and dopamine) during HD session using glucose-free dialysate and then switched to 5.55 mmol/L glucose-containing dialysate. One-way analysis of variance (ANOVA) was used to identify the effect of two dialysates on the intra-dialysis changes of hepcidin-25 and catecholamines. Spearman and Pearson correlation coefficients were performed to detect the relationships between hepcidin-25 and catecholamines. Glucose-free dialysate achieved a greater reduction of hepcidin-25 than 5.55 mmol/L glucose-containing dialysate in a single bicarbonate HD session [-8.43 (-15.44 to -1.42) vs. 0.46 (-6.09 to 7.00) %, P < .05]. The intra-dialysis changes of catecholamines showed no significant differences between the two dialysates. The serum hepcidin-25 levels were positively associated with plasma catecholamines levels at pre-, intra- and post-HD (R = 0.22~0.62 with P < .05). Our findings suggest that glucose-containing dialysate might up-regulate hepcidin-25 synthesis through activation of the sympathetic nervous system or oxidative stress, possibly mediated by increased production of catecholamines. Adequately designed studies are needed to confirm and reveal the mechanisms of dialysate glucose concentration on hepcidin-25 kinetics during HD sessions.

Myocardial dysfunction is a leading cause of mortality in chronic kidney disease (CKD) children specially those on regular hemodialysis. Cardiac biomarkers play a key role for early detection of myocardial injury. We aim to clarify the prognostic role of circulating cardiac biomarkers, heart type fatty acid binding protein (H-FABP) and pregnancy associated plasma protein-A (PAPP-A) in CKD children on regular hemodialysis. This is a prospective case control study over 2 years duration. Initial assessment included 20 CKD children on regular hemodialysis and 20 age- and sex- matched healthy children as a control group. Serum level of H-FABP and PAPP-A were measured and correlated to conventional echocardiographic findings and cardiovascular outcome in CKD children. 60% of CKD children developed cardiovascular comorbidities. H-FABP and PAPP-A levels were significantly elevated especially in those with worse cardiovascular outcome. H-FABP and PASP-A levels were positively correlated with LVM index. At cut off point > 17.65 pg/mL, H-FABP has 91% sensitivity and 87.5% specificity for prediction of cardiac morbidity. Elevated H-FABP (OR = 33; CI 95%: 2.455 - 443.591), LVM indexed to body surface area (OR = 21; CI 95%: 1.777 - 248.103), LVM indexed to lean body mass (OR = 15; CI 95%: 1.652 -136.172), elevated PAPP-A (OR = 9.8; CI 95%: 0.898 - 106.845) and Hypertension (OR = 8.333; CI 95%: 1.034 - 67.142) are the main risk factors for cardiac morbidities in CKD children. Elevated H-FABP and PAPP-A are valuable prognostic markers for cardiovascular outcome in CKD children on regular hemodialysis.

Acute kidney injury is manifested by sudden deterioration of kidney functions, with or without reduction of urine output. The spectrum of injury ranges from mild to severe, sometimes requires renal replacement therapy. The initial workup includes a patient history to identify the use of nephrotoxic medications or systemic illnesses that may cause poor renal perfusion or directly impair renal function. Formaldehyde which present in cosmetic products; is toxic to many parts including respiratory, renal, and neurologic systems. Here, we have reported 2 cases of acute kidney injury (AKI) after using formaldehyde free hair straightening protein presented with acute tubular injury, responded to corticosteroid therapy.

McKittrick-Wheelock syndrome is a rare complication of rectosigmoid villous adenoma leading to secretory diarrhea, prerenal acute kidney injury and severe fluid and electrolyte imbalances. There are about 50 cases reported in literature. We represent a case of 71 year-old patient with persistant chronic diarrhea, prerenal azotemia, severe hypokalemia, and hyponatremia. Initially, the patient's kidney function and serum potassium values were normalized by conservative treatment, and villous adenoma was removed by surgery.

While terminal complement blockade with Eculizumab is the first line therapy for atypical HUS (Haemolytic uremic syndrome), lack of its availability and cost limits its use. Plasma exchange becomes a first line modality in the current scenario. However, exposure to large volumes of allogenic plasma and lack of skilled manpower are the limiting factors associated with it. Moreover, there is a subset of patients who fail to respond to plasma exchange.
Treatment and follow up records of the children with atypical HUS who did not respond to daily plasma exchange therapy and their course during follow up was reviewed.
Three children with positive anti-complement factor H antibody atypical HUS did not respond to daily plasma exchange and were Rituximab administered after completing five daily treatments. It was seen that these children, initially non-responsive to plasma therapy, attained remission after Rituximab and did not require further plasma exchanges. The remission was sustained in long term with a follow up of 7 years, 4 years and 6 months respectively. Rituximab might be a useful alternative in inducing haematological remission in children with poor or no response to plasma therapy. This abbreviates the duration of plasma exchange, which not only avoids complications due to prolonged plasma therapy but also helps reducing the cost of therapy.