A case report of mediastinal parathyroid carcinoma in a chronic kidney disease patient: Addressing management conundrum.

Parathyroid carcinoma is a rare malignancy; and it is rarer to find one located in an ectopic location. Ectopic parathyroid glands are a reported cause of failed primary surgery for hyperparathyroidism. We report here a 73-year-old male who previously had parathyroidectomy for primary hyperparathyroidism but then had recurrence of his symptoms with a diagnosis of a mediastinal parathyroid carcinoma on further evaluation. This presentation of complicated mediastinal parathyroid carcinoma posed significant diagnostic and management challenges due to comorbid stage IV chronic kidney disease (CKD). Secondly, due to the same comorbid condition, a more aggressive calcimimetic regimen could not be undertaken due to the risk of renal dysfunction with potential progression to dialysis status. Thirdly, he was a high-risk surgical candidate due to significant cardiovascular risks. Ideally, open surgical intervention would be recommended but due to the associated risks, he was managed with robotic-assisted thoracoscopic surgery. He subsequently developed hypocalcemia which normalized with supplemental calcium at follow-up.

Central vein stenosis in hemodialysis vascular access: clinical manifestations and contemporary management strategies.

Central venous stenosis is a significant and frequently encountered problem in managing hemodialysis (HD) patients. Venous hypertension, often accompanied by severe symptoms, undermines the integrity of the hemodialysis access circuit. In central venous stenosis, dialysis through an arteriovenous fistula is usually inefficient, with high recirculation rates and prolonged bleeding after dialysis. Central vein stenosis is a known complication of indwelling intravascular and cardiac devices, such as peripherally inserted central catheters, long-term cuffed hemodialysis catheters, and pacemaker wires. Hence, preventing this challenging condition requires minimization of central venous catheter use. Endovascular interventions are the primary approach for treating central vein stenosis. Percutaneous angioplasty and stent placement may reestablish vascular function in cases of elastic and recurrent lesions. Currently, there is no consensus on the optimal treatment, as existing management approaches have a wide range of patency rates.

Pathophysiological concepts and screening of cardiovascular disease in dialysis patients.

Dialysis patients experience 10-20 times higher cardiovascular mortality than the general population. The high burden of both conventional and nontraditional risk factors attributable to loss of renal function can explain higher rates of cardiovascular disease (CVD) morbidity and death among dialysis patients. As renal function declines, uremic toxins accumulate in the blood and disrupt cell function, causing cardiovascular damage. Hemodialysis patients have many cardiovascular complications, including sudden cardiac death. Peritoneal dialysis puts dialysis patients with end-stage renal disease at increased risk of CVD complications and emergency hospitalization. The current standard of care in this population is based on observational data, which has a high potential for bias due to the paucity of dedicated randomized clinical trials. Furthermore, guidelines lack specific guidelines for these patients, often inferring them from non-dialysis patient trials. A crucial step in the prevention and treatment of CVD would be to gain better knowledge of the influence of these predisposing risk factors. This review highlights the current evidence regarding the influence of advanced chronic disease on the cardiovascular system in patients undergoing renal dialysis.

Acute kidney injury in diabetic patients: A narrative review.

Diabetes mellitus (DM) is the most common cause of chronic kidney disease, which leads to end-stage renal failure worldwide. Glomerular damage, renal arteriosclerosis, and atherosclerosis are the contributing factors in diabetic patients, leading to the progression of kidney damage. Diabetes is a distinct risk factor for acute kidney injury (AKI) and AKI is associated with faster advancement of renal disease in patients with diabetes. The long-term consequences of AKI include the development of end-stage renal disease, higher cardiovascular and cerebral events, poor quality of life, and high morbidity and mortality. In general, not many studies discussed extensively "AKI in DM." Moreover, articles addressing this topic are scarce. It is also important to know the cause of AKI in diabetic patients so that timely intervention and preventive strategies can be implemented to decrease kidney injury. Aim of this review article is to address the epidemiology of AKI, its risk factors, different pathophysiological mechanisms, how AKI differs between diabetic and nondiabetic patients and its preventive and therapeutic implications in diabetics. The increasing occurrence and prevalence of AKI and DM, as well as other pertinent issues, motivated us to address this topic.

Management of diabetic kidney disease: where do we stand?: A narrative review.

Diabetic kidney disease is the leading cause of chronic kidney disease and end-stage renal disease. The pathogenesis and risk factors for the development of diabetic kidney disease are complex and multifaceted, resulting in glomerular hypertrophy, tubulointerstitial inflammation, and fibrosis. The clinical staging progresses over 5 stages from early hyperfiltration to overt nephropathy. Primary prevention like glycaemic control, control of blood pressure, treatment of dyslipidemia and lifestyle modifications have shown promising benefits. Despite widespread research, very few drugs are available to retard disease progression. More literature and research are needed to fill these lacunae. We carried out a literature search focusing on newer updates in diabetic kidney disease pathophysiology, diagnosis and management using a PubMed search through the National library of medicine using keywords "Diabetic kidney disease," and "Diabetic nephropathy" till the year 2022. We have summarized the relevant information from those articles.

Contemporary review of management techniques for cephalic arch stenosis in hemodialysis.

The type of hemodialysis access and its preservation impact the quality of life and survival of patients undergoing hemodialysis. Vascular access complications are among the top causes of morbidity, hospitalization, and catheter use, with significant economic burden. Poor maturation and stenosis continue to be key impediments to upper arm arteriovenous fistula feasibility. Cephalic arch is a common location for vascular access dysfunction due to its distinctive anatomy, complex valves, and biochemical alterations attributable to renal failure. Understanding cephalic arch stenosis is critical due to its high prevalence and treatment failure. The appropriate management option is highly debatable and mostly dependent on patient characteristics and interventionist's preference. Current options include, percutaneous transluminal balloon angioplasty, stent grafts, bare metal stents, cutting balloon angioplasty, endovascular banding, and surgical procedures. This article discusses the etiologies of cephalic arch stenosis as well as currents trends in management including endovascular and surgical options.

Iatrogenic Fistula in Hemodialysis Patients: An Alternative Approach to Thrombectomy of Arteriovenous Graft (AVG) Thrombosis.

Arterial venous (AV) fistula is the first choice of vascular access to perform hemodialysis in the vast majority of suitable patients followed by arteriovenous grafts (AVG). An iatrogenic fistula can occur when a second vein adjacent to the graft is punctured and the needle traverses the vein. In normal circumstances, this has no clinical repercussions and does not need correction, and in prior reports, it has helped to maintain the patency of partially occluded grafts but rarely can lead to thrombosis of the graft due to reduced flow and pressure in the graft lumen. We report here what we believe is a unique approach to perform thrombectomy of an occluded graft in a 71-year-old patient on hemodialysis to avoid placement of tunneled hemodialysis catheters and complications associated with catheters. When the outflow of basilic vein in this patient was thrombosed and could not be traversed, we successfully used an iatrogenic fistula as main outflow vein for the graft and created an alternative vein for drainage thus avoiding placement of a tunneled catheter for hemodialysis.

Combination Treatment with Sodium Nitrite and Isoquercetin on Endothelial Dysfunction among Patients with CKD: A Randomized Phase 2 Pilot Trial.

BACKGROUND AND OBJECTIVES: Endothelial dysfunction is common among patients with CKD. We tested the efficacy and safety of combination treatment with sodium nitrite and isoquercetin on biomarkers of endothelial dysfunction in patients with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This randomized, double-blind, placebo-controlled phase 2 pilot trial enrolled 70 patients with predialysis CKD. Thirty-five were randomly assigned to combination treatment with sodium nitrite (40 mg twice daily) and isoquercetin (225 mg once daily) for 12 weeks, and 35 were randomly assigned to placebo. The primary outcome was mean change in flow-mediated vasodilation over the 12-week intervention. Secondary and safety outcomes included biomarkers of endothelial dysfunction, inflammation, and oxidative stress as well as kidney function, methemoglobin, and adverse events. Intention-to-treat analysis was conducted. RESULTS: Baseline characteristics, including age, sex, race, cigarette smoking, history of hypertension and diabetes, use of renin-angiotensin system blockers, BP, fasting glucose, lipid profile, kidney function, urine albumin-creatinine ratio, and endothelial biomarkers, were comparable between groups. Over the 12-week intervention, flow-mediated vasodilation increased 1.1% (95% confidence interval, -0.1 to 2.3) in the treatment group and 0.3% (95% confidence interval, -0.9 to 1.5) in the placebo group, and net change was 0.8% (95% confidence interval, -0.9 to 2.5). In addition, changes in biomarkers of endothelial dysfunction (vascular adhesion molecule-1, intercellular adhesion molecule-1, E-selectin, vWf, endostatin, and asymmetric dimethylarginine), inflammation (TNF-α, IL-6, C-reactive protein, IL-1 receptor antagonist, and monocyte chemoattractant protein-1), and oxidative stress (oxidized LDL and nitrotyrosines) were not significantly different between the two groups. Furthermore, changes in eGFR, urine albumin-creatinine ratio, methemoglobin, and adverse events were not significantly different between groups. CONCLUSIONS: This randomized phase 2 pilot trial suggests that combination treatment with sodium nitrite and isoquercetin did not significantly improve flow-mediated vasodilation or other endothelial function biomarkers but also did not increase adverse events compared with placebo among patients with CKD. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Nitrite, Isoquercetin, and Endothelial Dysfunction (NICE), NCT02552888.

The association of angiogenic factors and chronic kidney disease.

BACKGROUND: There are limited data on the associations of circulating angiogenic factors with chronic kidney disease (CKD). We investigate the associations of circulating vascular endothelial growth factor (VEGF)-A, angiopoietin-1, angiopoietin-1/VEGF-A ratio, VEGF receptor 1 (VEGFR-1), VEGFR-2, and pentraxin-3 with CKD. METHODS: We recruited 201 patients with CKD and 201 community controls without CKD from the greater New Orleans area. CKD was defined as estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 or presence of albuminuria. Multivariable quantile and logistic regression models were used to examine the relationship between angiogenesis-related factors and CKD adjusting for confounding factors. RESULTS: After adjusting for covariables including traditional cardiovascular disease (CVD) risk factors, C-reactive protein, and history of CVD, the medians (interquartile range) were 133.08 (90.39, 204.15) in patients with CKD vs. 114.17 (72.45, 170.32) pg/mL in controls without CKD (p = 0.002 for group difference) for VEGF-A; 3951.2 (2471.9, 6656.6) vs. 4270.5 (2763.7, 6537.2) pg/mL (p = 0.70) for angiopoietin-1; 25.87 (18.09, 47.90) vs. 36.55 (25.71, 61.10) (p = 0.0001) for angiopoietin-1/VEGF-A ratio; 147.81 (122.94, 168.79) vs. 144.16 (123.74, 168.05) ng/mL (p = 0.25) for VEGFR-1; 26.20 (22.67, 29.92) vs. 26.28 (23.10, 29.69) ng/mL (p = 0.31) for VEGFR-2; and 1.01 (0.79, 1.49)vs. 0.89 (0.58, 1.18) ng/mL (p = 0.01) for pentraxin-3, respectively. In addition, an elevated VEGF-A level and decreased angiopoietin-1/VEGF-A ratio were associated with increased odds of CKD. CONCLUSIONS: These data indicate that plasma VEGF-A and pentraxin-3 levels were increased and the angiopoietin-1/VEGF-A ratio was decreased in patients with CKD. Future prospective studies are warranted to examine whether angiogenic factors play a role in progression of CKD.

Pseudohyperkalemia: Look before you treat.

Pseudohyperkalemia is defined as a reported rise in serum potassium concentration along with a normal effective plasma potassium concentration. We present a case report of a 57-year-old gentleman with a history of chronic lymphocytic leukemia, who presented with an elevation in serum potassium along with a normal plasma potassium concentration. Through an exploration of the literature, we demonstrate that pseudohyperkalemia is an important phenomenon to watch for as it may sometimes lead to unnecessary and potentially dangerous treatment.

Systematic oral hydration with water is similar to parenteral hydration for prevention of contrast-induced nephropathy: an updated meta-analysis of randomised clinical data.

BACKGROUND: Contrast-induced nephropathy (CIN) is the third most common cause of hospital-acquired kidney injury and is related to increased long-term morbidity and mortality. Adequate intravenous (IV) hydration has been demonstrated to lessen its occurrence. Oral (PO) hydration with water is inexpensive and readily available but its role for CIN prevention is yet to be determined. METHODS: PubMed, EMBASE and the Cochrane Central register of controlled trials (CENTRAL) databases were searched until April 2015 and studies were selected using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. All randomised clinical trials with head-to-head comparison between PO and IV hydration were included. RESULTS: A total of 5 studies with 477 patients were included in the analysis, 255 of those receiving PO water. The incidence of CIN was statistically similar in the IV and PO arms (7.7% and 8.2%, respectively; relative risk 0.97; 95% CI 0.36 to 2.94; p=0.95). The incidence of CIN was statistically similar in the IV and PO arms in patients with chronic kidney disease and with normal renal function. Rise in creatinine at 48-72 h was lower in the PO hydration group compared with IV hydration (pooled standard mean difference 0.04; 95% CI 0.03 to 0.06; p<0.001; I(2)=62%). CONCLUSIONS: Our meta-analysis shows that systematic PO hydration with water is at least as effective as IV hydration with saline to prevent CIN. PO hydration is cheaper and more easily administered than IV hydration, thus making it more attractive and just as effective.

Comparison of Cutting Balloon Angioplasty and Percutaneous Balloon Angioplasty of Arteriovenous Fistula Stenosis: A Meta-Analysis and Systematic Review of Randomized Clinical Trials.

BACKGROUND: Hemodialysis (HD) access failure is a common cause of increased morbidity and healthcare cost in patients with end stage renal disease (ESRD). Percutaneous balloon angioplasty has been used to treat hemodialysis access stenosis but is complicated by a high rate of restenosis. Percutaneous cutting balloon (PCB) angioplasty is an alternative approach that has shown to reduce restenosis. OBJECTIVES: The aim of the study is to assess the safety and efficacy of PCB angioplasty in comparison with conventional and high-pressure balloon angioplasty in the treatment of hemodialysis access site stenosis. METHODS: We searched PubMed, EMBASE and the Cochrane Central register of controlled trials (CENTRAL) databases through August 2014 and selected studies using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. We included all randomized clinical trials with a head-to-head comparison between PCB and conventional or high-pressure balloon angioplasty RESULTS: Three studies with 1034 participants (age 60.7 (±12.9) years and 50.1% males) with 525 in PCB and 509 in control arm were included in the analysis. The immediate procedural success rate was not significantly different in the PCB angioplasty and control arm respectively, (87.2% vs. 83.7% RD -0.02; 95%CI -0.06 to 0.01; P = 0.38). The six-month target lesion patency was significantly higher in the PCB angioplasty arm (67.2% vs. 55.6% RD 0.12; 95%CI 0.05-0.19; P < 0.05) with number needed to treat (NNT) of 9. The device related complications were not statistically significant between groups (RD 0.03; 95%CI -0.02 to 0.07; P = 0.26). CONCLUSIONS: PCB angioplasty is effective in treatment of hemodialysis access stenosis, with significantly higher six-month patency compared to balloon angioplasty.

Trimetazidine Decreases Risk of Contrast-Induced Nephropathy in Patients With Chronic Kidney Disease: A Meta-Analysis of Randomized Controlled Trials.

OBJECTIVES: We sought to synthesize and analyze the available data from randomized controlled trials (RCTs) for trimetazidine (TMZ) in the prevention of contrast-induced nephropathy (CIN). BACKGROUND: Contrast-induced nephropathy after coronary angiography is associated with poor outcomes. Trimetazidine is an anti-ischemic drug that might reduce incidence of CIN, but current data are inconclusive. METHODS: We searched MEDLINE/PubMed, EMBASE, Scopus, Cochrane Library, Web of Science, and ScienceDirect electronic databases for RCTs comparing intravenous hydration with normal saline (NS) and/or N-acetyl cysteine (NAC) versus TMZ plus NS ± NAC for prevention of CIN. We used RevMan 5.2 for statistical analysis with the fixed effects model. RESULTS: Of the 808 studies, 3 RCTs met criteria with 290 patients in the TMZ plus NS ± NAC group and 292 patients in the NS ± NAC group. The mean age of patients was 59.5 years, and baseline serum creatinine ranged from 1.3 to 2 mg/dL. Trimetazidine significantly reduced the incidence of CIN by 11% (risk difference 0.11; 95% confidence interval, 0.16-0.06; P < .01). There was no significant heterogeneity between the studies (I(2) statistic = 0). The number needed to treat to prevent 1 episode of CIN was 9. CONCLUSIONS: The addition of TMZ to NS ± NAC significantly decreased the incidence of CIN in patients undergoing coronary angiography. In conclusion, TMZ could be considered as a potential tool for prevention of CIN in patients with renal dysfunction.

Long-term outcome of ketoconazole and tacrolimus co-administration in kidney transplant patients.

AIM: To study the long-term outcome of ketoconazole and tacrolimus combination in kidney transplant recipients. METHODS: From 2006 to 2010, ketoconazole was given in 199 patients and was continued for at least 1 year or until graft failure (Group 1), while 149 patients did not receive any ketoconazole (Group 2). A combination of tacrolimus, mycophenolate and steroid was used as maintenance therapy. High risk patients received basiliximab induction. RESULTS: Basic demographic data was similar between the 2 groups. The 5-year cumulative incidence of biopsy-confirmed and clinically-treated acute rejection was significantly higher in Group 1 than in Group 2 (34% vs 18%, P = 0.01). The 5-year Kaplan-Meier estimated graft survival (74.3% vs 76.4%, P = 0.58) and patient survival (87.8% vs 87.5%, P = 0.93) were not different between the 2 groups. Multivariable analyses identified ketoconazole usage as an independent risk of acute rejection (HR = 2.33, 95%CI: 1.33-4.07; P = 0.003) while tacrolimus dose in the 2(nd) month was protective (HR = 0.89, 95%CI: 0.75-0.96; P = 0.041). CONCLUSION: Co-administration of ketoconazole and tacrolimus is associated with significantly higher incidence of acute rejection in kidney transplant recipients.

Fragmented QRS complexes-a novel but underutilized electrocardiograhic marker of heart disease.

The electrocardiogram is the mainstay approach for diagnosing a myocardial infarction (MI). The diagnosis of an old MI and the identification of myocardial scar via the electrocardiogram are difficult because there are no other specific signs for a non-Q-wave MI. In this article, we will review the fragmented QRS and its role in identifying myocardial scar and depolarization abnormalities in patients with coronary artery disease.

Essential concept of transplant immunology for clinical practice.

Our understanding of transplant immunology has advanced from gross allograft rejection to cellular response and to current molecular level. More sensitive assays have been developed to characterize patient sensitization and to detect pre-existing donor-specific antibodies (DSA) in pre-transplant crossmatch. After a transplant, pre-existing or de novo DSA are increasingly monitored to guide clinical management. Therefore, it is important for clinicians to understand the basic concepts and key components of transplant immunology as well as be familiarized with the modern immunological techniques used in kidney transplantation.

"Perilous pearl"--papillary fibroelastoma of aortic valve: a case report and literature review.

Papillary fibroelastomas of the heart valves are benign, slow-growing, rare tumors of the heart. These lesions are primarily responsible for embolic events that can clinically manifest with neurological and cardiovascular symptoms. Early diagnosis is very important, as surgical excision of these tumors can prevent cerebrovascular and cardiovascular complications. The case of a 60-year-old man who presented with a neurological deficit caused by a papillary fibroelastoma of the noncoronary cusp of the aortic valve is described. Diagnosis was made by transesophageal echocardiogram, and the tumor was resected surgically.

Cardioprotection by sulfaphenazole, a cytochrome p450 inhibitor: mitigation of ischemia-reperfusion injury by scavenging of reactive oxygen species.

Cytochrome P450 (P450) enzymes play a significant role in promoting myocardial ischemia-reperfusion (I/R) injury. CYP2C9, an isoform of P450, is known to generate superoxide radicals in the reperfused heart. Sulfaphenazole (SPZ), a CYP2C9 inhibitor, has been shown to decrease I/R injury; however, the mechanism of cardioprotection by SPZ is not well elucidated. The objective of this study was to test whether SPZ mitigates myocardial I/R injury by scavenging reactive oxygen species (ROS). Isolated rat hearts were subjected to 30 min of global ischemia followed by 45 min of reperfusion. Hearts were perfused with SPZ and/or N(omega)-nitro-L-arginine methylester (L-NAME). Coronary flow (CF), left-ventricular developed pressure (LVDP), and rate-pressure product (RPP) were monitored. Superoxide and nitric oxide (NO) generation in the reperfused tissue was determined using fluorescence methods. Myocardial infarct size was measured using triphenyltetrazolium chloride staining. The SPZ-treated group showed a significant recovery of cardiac function compared with the untreated I/R group (CF, 53 versus 45%; LVDP, 48 versus 22%; RPP, 51 versus 20%). The infarct size was significantly reduced in the SPZ-treated group (15%) compared with the I/R control (42%). Coadministration of L-NAME with SPZ significantly attenuated the beneficial effects of SPZ. In addition, SPZ treatment showed significantly decreased superoxide levels and enhanced NO bioavailability in the reperfused heart. In conclusion, the protective effect of SPZ against I/R-mediated myocardial damage appears to be due to a reduction in the superoxide level caused by its inhibition of CYP2C9, as well as scavenging of oxygen free radicals generated in the reperfused heart.

Prevention of postischemic myocardial reperfusion injury by the combined treatment of NCX-4016 and Tempol.

Nitric oxide (NO) plays a protective role in myocardial ischemia-reperfusion (I/R) injury. However, the concomitant production of superoxide and other reactive oxygen species (ROS) during I/R may diminish the bioavailability of NO and hence compromise the beneficial effects. The objective of this study was to investigate the protective effect of the coadministration of NCX-4016 [2-(acetyloxy)benzoic acid 3-(nitrooxymethyl)phenyl ester] (an NO donor) with antioxidants Tempol, superoxide dismutase (SOD), or urate on I/R injury. Isolated rat hearts, perfused with Krebs-Henseleit buffer, were subjected to 30 minutes of global ischemia, followed by 45 minutes of reperfusion. Before the induction of ischemia, the hearts were infused for 1 minute with NCX-4016 (100 microM) either alone or in combination with Tempol (100 microM), SOD (200 U/mL), or urate (100 microM). Hearts pretreated with NCX-4016 showed a significantly enhanced recovery of function and decreased infarct size and LDH/CK release compared with the controls. However, treatment of hearts with NCX-4016 + Tempol, SOD, or urate showed a significantly enhanced recovery of heart function compared with NCX-4016 alone. The treatment of hearts with NCX-4016 + Tempol showed significantly enhanced NO generation and decreased ROS and dityrosine (a marker of peroxynitrite) formation. In conclusion, NCX-4016 in combination with Tempol demonstrated significant cardioprotection and, thus, may offer a novel therapeutic strategy to prevent I/R-mediated myocardial injury.