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1.  Use of the Tego needlefree connector is associated with reduced incidence of catheter-related bloodstream infections in hemodialysis patients 
Background and objectives
Catheter-related bloodstream infections (CRBSIs) are common in hemodialysis patients using central venous catheters, and catheter occlusion also occurs frequently. The Tego needlefree connector was developed to reduce the incidence of these complications; however, existing studies of its effectiveness and safety are limited.
Materials and methods
This retrospective analysis compared outcomes among patients of a large dialysis organization receiving in-center hemodialysis using a central venous catheter with either the Tego connector or standard catheter caps between October 1 and June 30, 2013. Incidence rates for intravenous (IV) antibiotic starts, receipt of an IV antibiotic course, positive blood cultures, mortality, and missed dialysis treatments were calculated, and incidence-rate ratios (IRRs) were estimated using Poisson regression models. Utilization of erythropoiesis-stimulating agents (ESAs) and thrombolytics was described for each patient-month and compared using mixed linear models. Models were run without adjustment, adjusted for covariates that were imbalanced between cohorts, or fully adjusted for all potential confounders.
The analysis comprised 10,652 Tego patients and 6,493 controls. Tego use was independently associated with decreased risk of CRBSI, defined by initiation of IV antibiotics (adjusted IRR 0.92, 95% confidence interval [CI] 0.87–0.97) or initiation of IV antibiotic course (adjusted IRR 0.89, 95% CI 0.84–0.95). Tego use was independently associated with decreased rate of missed dialysis treatments (adjusted IRR 0.98, 95% CI 0.97–1.00); no significant difference between Tego and control cohorts was observed with respect to mortality. Tego use was associated with decreased likelihood of thrombolytic use (adjusted per-month probability of 5.6% versus 6.2% for controls) and lower utilization of ESAs in study months 7–9.
Use of the Tego connector may reduce the risk of CRBSI and result in lower utilization of thrombolytics, antibiotics, and ESAs, as well as fewer missed dialysis treatments.
PMCID: PMC3979783
catheter; dialysis; end-stage renal disease; ESA; infection; mortality
2.  The pleiotropic effects of the hydroxy-methyl-glutaryl-CoA reductase inhibitors in renal disease 
It is well known that statins exert their main effect by inhibiting cholesterol synthesis through the inhibition of the 3-hydroxy-3-methyl-glutaryl-CoA reductase enzyme. The pleiotropic effects of statins, which are independent of their inhibition of cholesterol synthesis, have explained many of the beneficial effects of these drugs in a variety of disorders such as malignancies, infection, and sepsis, as well as in cardiovascular and rheumatologic disorders. However, the role of these drugs in renal disorders remains controversial. In the present review, we examine the most recent findings involving statins and renal disease among different clinical scenarios, including chronic kidney disease, contrast-induced nephropathy, renal injury after coronary artery bypass surgery, and renal transplant patients.
PMCID: PMC3974687
kidney disease; statins; renal transplant
3.  Lupus nephritis flare in young patients: relapse or nonadherence to treatment? 
Adherence is a challenging issue in the treatment of systemic lupus erythematosus. Nonadherence has been widely addressed in patients with lupus and must be detected quickly to prevent severe complications. The cases we present illustrate the importance of adherence in young adults.
Case 1
A 23-year-old Spanish woman diagnosed with severe lupus nephritis 8 years previously achieved renal remission after immunosuppressive treatment with corticosteroids and cyclophosphamide. Three years later, she developed a renal flare. Her treatment was intensified, and rituximab and mycophenolate mofetil were added. One year later, she was readmitted for a new renal flare. A blood test revealed no detectable levels of mycophenolic acid, and the patient admitted she had not taken her treatment correctly. Treatment was resumed. Four years later, the patient remains in remission.
Case 2
A 19-year-old Spanish woman was diagnosed with nephrotic syndrome due to lupus nephritis. She achieved complete remission after treatment with corticosteroids and cyclophosphamide followed by mycophenolate mofetil. Two years later, she developed a severe renal relapse that was treated with corticosteroids, cyclophosphamide, and rituximab. The response to treatment was good. Mycophenolic acid was undetectable in blood. The patient admitted that she had often missed doses before this relapse. The renal response has been maintained since she resumed her previous medications 2 years ago.
We conclude that the frequent and severe relapses of lupus nephritis observed in young patients may actually be due to nonadherence rather than to refractory disease. Our cases are typical examples of nonadherence that were discovered after a detailed interview with the patients and their families. We emphasize the need for clinical suspicion of nonadherence when caring for young adults with lupus.
PMCID: PMC3974696
lupus nephritis; renal flare; nonadherence
4.  Tubulointerstitial disease in diabetic nephropathy 
Diabetes mellitus is the major cause of end stage renal disease (ESRD). We cannot predict which patient will be affected. ESRD patients suffer an extremely high mortality rate, due to a very high incidence of cardiovascular disease. Several randomized, prospective studies have been conducted to quantify the impact of strict glycemic control on morbidity and mortality, and have consistently demonstrated an association between strict glycemic control and a reduction in ESRD. Within the past 20 years, despite the implementation of treatments that were presumed to be renoprotective, diabetes mellitus has continued to rank as the leading cause of ESRD, which clearly indicates that we are still far from understanding the mechanisms involved in the initiation of ESRD. Progressive albuminuria has been considered as the sine qua non of diabetic nephropathy, but we know now that progression to diabetic nephropathy may well happen in the absence of initial microalbuminuria. The search for new biomarkers of early kidney damage has received increasing interest, since early identification of the pathways leading to kidney damage may allow us to adopt measures to prevent the development of ESRD. Most of these biomarkers are deeply influenced by environment, genetics, sex differences, and so on, making it extremely difficult to identify the ideal biomarker to target. At present, there are no new drugs that come close to providing the solutions we desire for our patients (ie, reducing complications). Even when used in combination with standard care, renal complications are, at best, only modestly reduced, at the considerable expense of additional pill burden and exposure to serious off-target effects. In this review, some of the hypothesized mechanisms of this heterogeneous disease will be considered, with particular attention to the tubule–interstitial compartment.
PMCID: PMC3968088
TGF-β1; ESRD; Ox-LDL; diabetes; ESRD
5.  Higher diastolic blood pressure at admission and antiedema therapy is associated with acute kidney injury in acute ischemic stroke patients 
Antiedema therapy with mannitol and furosemide is widely used for prevention and management of cerebral edema, elevated intracranial pressure, and cerebral hernia. There are some reports about mannitol and furosemide as risk factors of acute kidney injury (AKI). We investigated the risk factors for AKI including antiedema therapy in acute ischemic stroke patients. The subjects were 129 patients with acute ischemic stroke including 56 females and 73 males with a mean age 68.16±12.29 years. Patients were divided into two groups: patients with AKI and without AKI according to Acute Kidney Injury Network criteria. All patients had undergone cranial, carotid, and vertebral artery evaluation with magnetic resonance imaging. The number of patients with AKI was 14 (10.9%). Subjects experiencing atrial fibrillation (P=0.043) and higher diastolic blood pressure (DBP) (P=0.032) treated with mannitol (P=0.019) and furosemide (P=0.019) disclosed significant association with AKI. Regression analysis revealed that higher DBP (P=0.029) and management with mannitol (P=0.044) were the risk factors for AKI. Higher DBP at admission is the most important risk factor for AKI. However antiedema therapy should be used carefully in patients with acute ischemic stroke. Serum creatinine levels or estimated glomerular filtration rate should be watched frequently to prevent AKI.
PMCID: PMC3933720  PMID: 24570596
furosemide; mannitol; renal failure; cerebrovascular disease
6.  Revascularization as a treatment to improve renal function 
An aging atherosclerosis-prone population has led to an increase in the prevalence of atherosclerotic renovascular disease (ARVD). Medical management of this disease, as with other atherosclerotic conditions, has improved over the past decade. Despite the widespread availability of endovascular revascularization procedures, there is inconsistent evidence of benefit in ARVD and no clear consensus of opinion as to the best way to select suitable patients for revascularization. Several published randomized controlled trials have attempted to provide clearer evidence for best practice in ARVD, but they have done so with varying clarity and success. In this review, we provide an overview of ARVD and its effect on renal function. We present the currently available evidence for best practice in the management of patients with ARVD with a particular focus on revascularization as a treatment to improve renal function. We provide a brief overview of the evidence for revascularization in other causes of renal artery stenosis.
PMCID: PMC3933706  PMID: 24600242
renal artery stenosis; revascularization; atherosclerotic renovascular disease; fibromuscular dysplasia
7.  Obesity, hypertension, and chronic kidney disease 
Obesity is a major risk factor for essential hypertension, diabetes, and other comorbid conditions that contribute to development of chronic kidney disease. Obesity raises blood pressure by increasing renal tubular sodium reabsorption, impairing pressure natriuresis, and causing volume expansion via activation of the sympathetic nervous system and renin–angiotensin–aldosterone system and by physical compression of the kidneys, especially when there is increased visceral adiposity. Other factors such as inflammation, oxidative stress, and lipotoxicity may also contribute to obesity-mediated hypertension and renal dysfunction. Initially, obesity causes renal vasodilation and glomerular hyperfiltration, which act as compensatory mechanisms to maintain sodium balance despite increased tubular reabsorption. However, these compensations, along with increased arterial pressure and metabolic abnormalities, may ultimately lead to glomerular injury and initiate a slowly developing vicious cycle that exacerbates hypertension and worsens renal injury. Body weight reduction, via caloric restriction and increased physical activity, is an important first step for management of obesity, hypertension, and chronic kidney disease. However, this strategy may not be effective in producing long-term weight loss or in preventing cardiorenal and metabolic consequences in many obese patients. The majority of obese patients require medical therapy for obesity-associated hypertension, metabolic disorders, and renal disease, and morbidly obese patients may require surgical interventions to produce sustained weight loss.
PMCID: PMC3933708  PMID: 24600241
visceral adiposity; type II diabetes; sodium reabsorption; glomerular filtration rate; sympathetic nervous system; renin–angiotensin–aldosterone system
8.  Descriptive study of clinical profile and benefit of therapy in childhood hypercalciuria 
Clinical, biochemical, and ultrasonographic findings in 91 consecutive children presenting with hypercalciuria were analyzed along with the results of treatment to determine the clinical profile of hypercalciuria and its outcome. Hypercalciuria was common in children aged 1–5 years (39.6%), and hematuria was the most frequent symptom. There was no significant difference between 24-hour urinary calcium and random urinary calcium/creatinine ratio values between males and females. The random urinary calcium/creatinine ratio was found to be useful for screening and also for documenting the benefit of therapy. The children were essentially treated with thiazides, and the majority showed a good response, with a good overall outcome on follow-up.
PMCID: PMC3923610  PMID: 24532972
hematuria; hypercalciuria; thiazides
9.  Renal manifestations of genetic mitochondrial disease 
Mitochondrial diseases can be related to mutations in either the nuclear or mitochondrial genome. Childhood presentations are commonly associated with renal tubular dysfunction, but renal involvement is less commonly reported outside of this age-group. Mitochondrial diseases are notable for the significant variability in their clinical presentation and the broad spectrum of genes implicated in their etiology. These features contribute to the challenges of establishing a definitive diagnosis and understanding the pathogenetic mechanisms leading to kidney involvement in these diseases. Here, we review the deoxyribonucleic acid variants in the mitochondrial and nuclear genomes that have been associated with a kidney phenotype, and examine some of the possible pathogenic mechanisms that may contribute to the expression of a renal phenotype.
PMCID: PMC3916636  PMID: 24516335
genetics; kidney; mitochondria
10.  AST-120 for the management of progression of chronic kidney disease 
Uremic toxins such as indoxyl sulfate contribute to the pathogenesis of chronic kidney disease (CKD) by promoting glomerulosclerosis and interstitial fibrosis with loss of nephrons and vascular damage. AST-120, an orally administered intestinal sorbent, adsorbs indole, a precursor of indoxyl sulfate, thereby reducing serum and urinary concentrations of indoxyl sulfate. AST-120 has been available in Japan since 1991, and subsequently Korea (2005), and the Philippines (2010) as an agent to prolong the time to initiation of hemodialysis and for improvement of uremic symptoms in patients with CKD. A Medline search was performed to identify data supporting clinical experience with AST-120 for managing CKD. Prospective open-label and double-blind trials as well as retrospective analyses were included. In prospective trials and retrospective analyses, AST-120 has been shown to prolong the time to initiation of hemodialysis, and slow decline in glomerular filtration rate and the increase serum creatinine. In an initial randomized, double-blind, placebo-controlled trial in the United States, AST-120 was associated with a significant dose-dependent reduction in serum indoxyl sulfate levels and a decrease in uremia-related malaise. The Evaluating Prevention of Progression in CKD (EPPIC) trials, two double-blind, placebo-controlled trials undertaken in North America/Latin America and Europe, are evaluating the efficacy of AST-120 for preventing the progression of CKD. The results of the EPPIC trials will further define the role of AST-120 in this debilitating condition.
PMCID: PMC3912158  PMID: 24501542
AST-120; chronic kidney disease; hemodialysis; indoxyl sulfate; uremic toxin
11.  Bilateral renal artery thrombosis in inherited thrombophilia: a rare cause of acute kidney injury 
We describe the case of a 47-year-old man who developed significant acute, and subsequently chronic, kidney injury due to bilateral renal infarction. This occurred in the context of a combined inherited thrombophilia including antithrombin III deficiency and a prothrombin gene mutation. Bilateral renal artery thrombosis developed despite prophylactic treatment for thromboembolism. Arterial thrombosis is rare in the context of inherited thrombophilia and bilateral renal infarction is an unusual cause of acute kidney injury. Bilateral renal infarction due to primary renal artery thrombosis has not been previously described in antithrombin III deficiency, either as an isolated defect or in combination with other hereditary thrombophilia.
PMCID: PMC3900314  PMID: 24465133
renal infarction; renal thrombosis; AKI; antithrombin; prothrombin
12.  Microvascular pericytes in healthy and diseased kidneys 
Pericytes are interstitial mesenchymal cells found in many major organs. In the kidney, microvascular pericytes are defined anatomically as extensively branched, collagen-producing cells in close contact with endothelial cells. Although many molecular markers have been proposed, none of them can identify the pericytes with satisfactory specificity or sensitivity. The roles of microvascular pericytes in kidneys were poorly understood in the past. Recently, by using genetic lineage tracing to label collagen-producing cells or mesenchymal cells, the elusive characteristics of the pericytes have been illuminated. The purpose of this article is to review recent advances in the understanding of microvascular pericytes in the kidneys. In healthy kidney, the pericytes are found to take part in the maintenance of microvascular stability. Detachment of the pericytes from the microvasculature and loss of the close contact with endothelial cells have been observed during renal insult. Renal microvascular pericytes have been shown to be the major source of scar-forming myofibroblasts in fibrogenic kidney disease. Targeting the crosstalk between pericytes and neighboring endothelial cells or tubular epithelial cells may inhibit the pericyte–myofibroblast transition, prevent peritubular capillary rarefaction, and attenuate renal fibrosis. In addition, renal pericytes deserve attention for their potential to produce erythropoietin in healthy kidneys as pericytes stand in the front line, sensing the change of oxygenation and hemoglobin concentration. Further delineation of the mechanisms underlying the reduced erythropoietin production occurring during pericyte–myofibroblast transition may be promising for the development of new treatment strategies for anemia in chronic kidney disease.
PMCID: PMC3900313  PMID: 24465134
endothelial cell; fibroblast; chronic kidney disease; myofibroblast; renal fibrosis
13.  Proteinuria and its relation to cardiovascular disease 
Chronic kidney disease (CKD) and its associated morbidity pose a worldwide health problem. As well as risk of endstage renal disease requiring renal replacement therapy, cardiovascular disease is the leading cause of premature death among the CKD population. Proteinuria is a marker of renal injury that can often be detected earlier than any tangible decline in glomerular filtration rate. As well as being a risk marker for decline in renal function, proteinuria is now widely accepted as an independent risk factor for cardiovascular morbidity and mortality. This review will address the prognostic implications of proteinuria in the general population as well as other specific disease states including diabetes, hypertension and heart failure. A variety of pathophysiological mechanisms that may underlie the relationship between renal and cardiovascular disease have been proposed, including insulin resistance, inflammation, and endothelial dysfunction. As proteinuria has evolved into a therapeutic target for cardiovascular risk reduction in the clinical setting we will also review therapeutic strategies that should be considered for patients with persistent proteinuria.
PMCID: PMC3873205  PMID: 24379690
proteinuria; albuminuria; microalbuminuria; cardiovascular risk
14.  Clinical characteristics and outcomes of end-stage renal disease patients with self-reported pruritus symptoms 
One of the most common conditions affecting end-stage renal disease (ESRD) patients undergoing hemodialysis (HD) is pruritus. Studies report that itchy and dry skin, symptoms of pruritus, affect 40%–90% of ESRD patients. Yet, in clinical practice the condition is often underdiagnosed resulting in inadequate management and an underappreciated impact on patient outcomes. Two retrospective analyses were conducted: a preliminary analysis of ESRD patients with pruritus symptoms (n=73,124) undergoing HD or peritoneal dialysis at a large dialysis provider and a subsequent detailed analysis of a homogenous subset of patients undergoing in-center HD (n=38,315). The goal was to better understand the clinical burden of pruritus as it relates to patient characteristics, quality of life, medication use, and HD compliance. This population is commonly burdened by multiple comorbidities and related polypharmaceutical management; identifying the relationship of pruritus to these ailments can help guide future research and resource allocation. The detailed analysis confirmed trends observed in the preliminary analysis: 30% reported being “moderately” to “extremely bothered” by itchiness. The HD patient population with the highest severity of self-reported pruritus also had a consistent trend in overall increased resource utilization – higher monthly doses of erythropoietin-stimulating agents (53,397.1 to 63,405.4 units) and intravenous (IV) iron (237.2 to 247.6 units) and higher use of IV antibiotics (14.1% to 20.7%), as well as poorer quality-of-life measures (25-point reductions in Burden of Disease Score and Effects on Daily Life subscales of the Kidney Disease Quality of Life-36 survey). These results highlight the need to better identify and manage ESRD patients impacted by pruritus, as this symptom is associated with negative clinical outcomes and increased resource utilization. Further studies are needed to evaluate the current economic burden of pruritus in ESRD patients and create possible options for an improved pharmacoeconomic profile in this patient population.
PMCID: PMC3872274  PMID: 24379689
pruritus; end-stage renal disease; hemodialysis; itchiness; patient reported outcomes
15.  Long-term effect of cinacalcet hydrochloride on abdominal aortic calcification in patients on hemodialysis with secondary hyperparathyroidism 
Secondary hyperparathyroidism (SHPT) is one of the common complications in dialysis patients, and is associated with increased risk of vascular calcification. The effects of cinacalcet hydrochloride treatment on bone and mineral metabolism have been previously reported, but the benefit of cinacalcet on vascular calcification remains uncertain. The aim of this study was to evaluate the impact of cinacalcet on abdominal aortic calcification in dialysis patients.
Subjects and methods
Patients were on maintenance hemodialysis with insufficiently controlled SHPT (intact parathyroid hormone [PTH] >180 pg/mL) by conventional therapies. All subjects were initially administered 25 mg cinacalcet daily, with concomitant use of calcitriol analogs. Abdominal aortic calcification was annually evaluated by calculating aortic calcification area index (ACAI) using multidetector computed tomography (MDCT), from 12 months before to 36 months after the initiation of cinacalcet therapy.
Twenty-three patients were analyzed in this study. The mean age was 59.0±8.7 years, 34.8% were women, and the mean dialysis duration was 163.0±76.0 months. After administration of cinacalcet, serum levels of intact PTH, phosphorus, and calcium significantly decreased, and mean Ca × P values significantly decreased from 67.4±7.9 mg2/dL2 to 52±7.7 mg2/dL2. Although the ACAI value did not decrease during the observation period, the increase in ACAI between 24 months and 36 months after cinacalcet administration was significantly suppressed.
Long-term administration of cinacalcet was associated with reduced progression of abdominal aortic calcification, and achieving appropriate calcium and phosphorus levels may reduce the rates of cardiovascular events and mortality in patients on hemodialysis.
PMCID: PMC3872220  PMID: 24379691
abdominal aortic calcification; cinacalcet hydrochloride; hemodialysis
17.  Effects of dopamine on leptin release and leptin gene (OB) expression in adipocytes from obese and hypertensive patients 
A reduction of dopaminergic (DAergic) activity with increased prolactin levels has been found in obese and hypertensive patients, suggesting its involvement as a pathophysiological mechanism promoting hypertension. Similarly, leptin action increasing sympathetic activity has been proposed to be involved in mechanisms of hypertension. The aim of this study was to analyze the effects of DA, norepinephrine (NE), and prolactin on leptin release and leptin gene (OB) expression in adipocytes from obese and hypertensive patients.
Leptin release and OB gene expression were analyzed in cultured adipocytes from 16 obese and hypertensive patients treated with DA (0.001, 0.01, 0.1, and 1.0 μmol/L), NE (1.0 μmol/L), insulin (0.1 μmol/L), and prolactin (1.0 μmol/L), and from five nonobese and normotensive controls treated with DA (1 μmol/L), NE (1 μmol/L), insulin (0.1 μmol/L), and prolactin (1.0 μmol/L).
A dose-related reduction of leptin release and OB gene messenger ribonucleic acid expression under different doses of DA was observed in adipocytes from obese hypertensive patients. Whereas prolactin treatment elicited a significant increase of both leptin release and OB gene expression, NE reduced these parameters. Although similar effects of DA and NE were observed in adipocytes from controls, baseline values in controls were reduced to 20% of the value in adipocytes from obese hypertensive patients.
These results suggest that DAergic deficiency contributes to metabolic disorders linked to hyperleptinemia in obese and hypertensive patients.
PMCID: PMC3849084  PMID: 24348062
dopamine; leptin; cultured adipocytes; obesity; hypertension
18.  Features and outcomes of lupus nephritis in Morocco: analysis of 114 patients 
There is wide variation in clinical presentation and outcome of lupus nephritis (LN) among different ethnic groups. Few data for LN exist on North Africans, especially those from Morocco. The aim of our study was to review retrospectively the features and outcome of LN in Moroccan patients.
Patients and methods
We performed a single-center retrospective study. A total of 114 patients with LN were included. All patients met American Rheumatism Association criteria. LN was classified according to the International Society of Nephrology/Renal Pathology Society classification. We adopted previously defined outcome criteria for LN.
There were 101 females and 13 males, with a mean age of 29.9 years. At first presentation, we noted hypertension in 33%, hematuria in 76%, nephrotic syndrome in 53%, and renal failure in 60% of cases. Renal biopsy revealed predominant proliferative classes in more than 80% of patients. Patients received different regimens mainly based on intravenous cyclophosphamide. After a mean follow-up of 22 months, remission occurred in 45.5%, relapses in 82%, end-stage renal failure in 21%, and death in 16% of cases. Infection and neurological and cardiovascular diseases were the most frequent causes of death.
LN seems to be severe in our study, with a predominance of proliferative forms, severe renal manifestations, and poor renal and overall survival.
PMCID: PMC3839844  PMID: 24294005
lupus nephritis; systemic lupus erythematosus; nephritis
19.  Overcoming technical challenges when treating atypical hemolytic uremic syndrome with therapeutic plasma exchange 
Atypical hemolytic uremic syndrome (aHUS) is a very rare, life-threatening, progressive disease that frequently has a genetic component and in most cases is triggered by an uncontrolled activation of the complement system. Successful treatment of aHUS with plasma infusions and therapeutic plasma exchange (TPE) is well reported. TPE has been the treatment of choice in most adult patients with aHUS. However, due to severe hemolysis, which is common among aHUS patients, there are some technical challenges that can affect TPE treatment such as the continuous activation of the blood leak alarm due to hemolysis. Our experience shows that such patients can be managed better on a centrifuge based TPE machine compared to a membrane based TPE machine.
PMCID: PMC3838205  PMID: 24277990
atypical hemolytic uremic syndrome; aHUS; blood leak alarm; centrifuge based TPE; membrane based TPE; therapeutic plasma exchange; TPE
20.  A case of bismuth intoxication with irreversible renal damage 
Bismuth is a chemical element symbolized as Bi and is a trivalent poor metal, which chemically resembles arsenic and antimony. Colloidal bismuth subcitrate (CBS) and bismuth subsalicylate are the bismuth salts widely used in the treatment of peptic ulcers, functional dyspepsia, and chronic gastritis. Intoxications with CBS are rare. In a few case reports, acute renal failure was described, but the literature review revealed no chronic renal failure related to CBS intoxication. In this case report we present a 21-year old female with chronic renal failure after a one year follow-up of CBS intoxication.
PMCID: PMC3825672  PMID: 24232291
acute renal failure; bismuth; intoxication; chronic renal failure
21.  Urinary angiotensinogen is a marker for tubular injuries in patients with type 2 diabetes 
Urinary angiotensinogen has been reported as a marker for the activation of intrarenal renin–angiotensin system (RAS) in various kidney diseases. To investigate the importance of urinary angiotensinogen in diabetic nephropathy, we compared the urinary levels of angiotensinogen, albumin, and α1-microglobulin.
Materials and methods
Japanese patients with type 2 diabetes at various stages of nephropathy (n=85) were enrolled, and we measured albumin/creatinine ratio (ACR) and urinary excretion of angiotensinogen and α1-microglobulin. We also compared the clinical data of the patients treated with or without angiotensin II receptor blockers or angiotensin-converting enzyme inhibitors (RAS inhibitors [+], n=51; RAS inhibitors [−], n=34).
Urinary angiotensinogen levels positively correlated with ACR (r=0.367, P=3.84×10−4) and urinary α1-microglobulin (r=0.734, P=1.32 × 10−15), while they negatively correlated with estimated glomerular filtration ratio (eGFR) (r=−0.350, P=1.02 × 10−3) and high-density lipoprotein cholesterol (r=−0.216, P=0.049). Multiple regression analysis was carried out to predict urinary angiotensinogen levels by employing eGFR, ACR, and urinary α1-microglobulin as independent variables; only urinary α1-microglobulin entered the regression equation at a significant level. Although ACR was higher in the RAS inhibitors (+) group, urinary α1-microglobulin and angiotensinogen did not show significant increase in the RAS inhibitors (+) group.
Urinary angiotensinogen is well correlated with urinary α1-microglobulin and reflected the tubular injuries which may be associated with the intrarenal RAS activation in patients with type 2 diabetes.
PMCID: PMC3808213  PMID: 24174882
diabetic nephropathy; urinary biomarkers; renin–angiotensin system; angiotensinogen; α1-microglobulin; albumin
22.  Membranous glomerulopathy and treatment with Acthar®: a case study 
Treatment options for refractory membranous nephropathy are limited. Herein we describe the case of a 46-year-old white male with membranous nephropathy who progressed during 3 years of treatment with antihypertensive agents (specifically angiotensin-converting enzyme inhibitors and angiotensin receptor blockers), diuretics, simvastatin, prednisone, cyclosporine A, and mycophenolate mofetil. Prior to initiation of treatment with H.P. Acthar® Gel, his proteinuria level was 9,520 mg/dL (952.0 g/L) but it decreased to 2,948 mg/dL (294.8 g/L) after 10 months of Acthar therapy. After 13 months, treatment with Acthar was halted as his 24-hour urinary protein was 1,628 mg/dL (162.8 g/L); by 15 months, it was 407 mg/dL (40.7 g/L). The patient has remained free of signs and symptoms of membranous nephropathy for 1.5 years. These results support the use of Acthar as an effective and safe therapy for patients with refractory membranous nephropathy.
PMCID: PMC3808169  PMID: 24174881
membranous glomerulopathy; membranous nephropathy; ACTH; proteinuria; nephrotic syndrome
23.  Hemodialysis catheter implantation in the axillary vein by ultrasound guidance versus palpation or anatomical reference 
We compared the results of four different methods of hemodialysis catheter insertion in the medial segment of the axillary vein: ultrasound guidance, palpation, anatomical reference, and prior transient catheter.
All patients that required acute or chronic hemodialysis and for whom it was determined impossible or not recommended either to place a catheter in the internal jugular vein (for instance, those patients with a tracheostomy), or to practice arteriovenous fistula or graft; it was then essential to obtain an alternative vascular access. When the procedure of axillary vein catheter insertion was performed in the Renal Care Facility (RCF), ultrasound guidance was used, but in the intensive care unit (ICU), this resource was unavailable, so the palpation or anatomical reference technique was used.
Two nephrologists with experience in the technique performed 83 procedures during a period lasting 15 years and 8 months (from January 1997–August 2012): 41 by ultrasound guidance; 19 by anatomical references; 15 by palpation of the contiguous axillary artery; and 8 through a temporary axillary catheter previously placed. The ultrasound-guided patients had fewer punctures than other groups, but the value was not statistically significant. Arterial punctures were infrequent in all techniques. Analyzing all the procedure-related complications, such as hematoma, pneumothorax, brachial-plexus injury, as well as the reasons for catheter removal, no differences were observed among the groups. The functioning time was longer in the ultrasound-guided and previous catheter groups. In 15 years and 8 months of surveillance, no clinical or image evidence for axillary vein stenosis was found.
The ultrasound guide makes the procedure of inserting catheters in the axillary veins easier, but knowledge of the anatomy of the midaxillary region and the ability to feel the axillary artery pulse (for the palpation method) also allow relatively easy successful implant of catheters in the axillary veins.
PMCID: PMC3798232  PMID: 24143120
hemodialysis; catheter; axillary venous; ultrasound guidance
24.  Comparison of once daily versus twice daily olmesartan in patients with chronic kidney disease 
The effects of olmesartan (OLM) on blood pressure and kidney function in Japanese patients with chronic kidney disease (CKD) were compared between 20 mg twice daily (BID) and 40 mg once daily (QD) treatments.
The subjects were Japanese CKD patients with concurrent hypertension who had been treated with OLM 20 mg BID for at least 3 months on an outpatient basis (n=39). After a change in the treatment regimen to 40 mg OLM QD (after breakfast), blood pressure (BP) (n=39), morning home BP (n=13), estimated glomerular filtration rate (n=39), and urinary albumin-to-creatinine ratio (n=17) were monitored for 2 months.
No significant change in office (mean ± standard deviation [SD] [mmHg], 143.9 ± 18.8/75.7 ± 12.0 to 141.6 ± 16.1/74.7 ± 11.7, not significant [ns]) or early morning home (mean ± SD [mmHg], 133.8 ± 15.9/71.2 ± 11.5 to 133.8 ± 13.9/74.5 ± 10.5, ns) BP was observed 2 months after the change in dose. The estimated glomerular filtration rate increased significantly (mean ± SD, 49.0 ± 28.0 to 51.8 ± 27.0, P<0.05), whereas urinary albumin-to-creatinine ratio did not change significantly (mean ± SD, 0.551 ± 0.445 to 0.364 ± 0.5194, ns).
High-dose OLM administered BID and QD had similar effects on outpatient and early morning home BP in CKD patients, suggesting that the BID regimen can be safely changed to a QD regimen. For CKD patients with hypertension requiring continuous long-term treatment, the possibility that the QD regimen might bring a greater therapeutic effect was suggested. However, recognizing the best blood pressure control level for a CKD patient is still a matter of debate, and should ideally be personalized.
PMCID: PMC3797633  PMID: 24143121
high-dose angiotensin receptor blocker; hypertension; chronic kidney disease; compliance; olmesartan
25.  Renoprotective effects of telmisartan after unilateral renal ablation in rats 
The renoprotective function of the angiotensin II type 1 receptor blocker (ARB) is well-known in various studies, including the animal model of renal failure. However, detailed temporal changes of pathological and molecular findings after unilateral nephrectomy are not fully understood. The main purpose of this study was to clarify the renoprotective effects and pathological changes induced by the ARB in rat-remnant kidney (RK) tissues after unilateral nephrectomy, but not after a 5/6 nephrectomy.
Telmisartan, which is structurally and functionally unique among ARB, was used in this study. Three rat groups were examined: A) no ARB administrated (RK, n=21); B) continuous subcutaneous infusion of an ARB administrated (RK-ARB, n=21); and C) a sham-operated group (Sham). Renal function was evaluated by blood urea nitrogen (BUN) levels and creatinine clearance (Ccr). Fibrosis was evaluated by hydroxyproline levels and Masson’s trichrome staining. Expressions of angiotensin II type 1 receptor (AT1R) and transforming growth factor beta (TGF-β) were investigated by real-time polymerase chain reaction and Western blotting.
There was no significant difference regarding body and kidney weight or pathological features evaluated by hematoxylin and eosin staining between the RK and RK-ARB groups. The Ccr in the RK group was significantly lower than that in the Sham group (P<0.01), but no significant difference was found between the RK-ARB and Sham groups. The fibrotic area increased significantly with time after nephrectomy in the RK group. Although a similar trend was found in the RK-ARB group, the percentage of fibrous area in the RK-ARB group was significantly lower than that in the RK group at each time point (P<0.01). AT1R mRNA levels in the RK group were regulated immediately compared with those in the RK-ARB group. Although expressions of the AT1R and TGF-β were significantly higher in the RK-ARB group than in the Sham group, no significant differences were found between the RK-ARB and Sham group.
The ARB had renoprotective effects after unilateral nephrectomy. The ARB effectively maintained Ccr. Our results also showed the possibility that fibrotic changes mediated by AT1R and TGF-β play an important role in renal protection. Moreover, this is the first report on changes of AT1R expression after using the ARB telmisartan in kidney tissues after unilateral nephrectomy. Finally, our results suggest that ARB may be useful to prevent renal failure in patients treated with nephrectomy.
PMCID: PMC3797634  PMID: 24143119
unilateral nephrectomy; telmisartan; angiotensin II type 1 receptor; renoprotection; fibrosis

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