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1.  Successful creation of an anemia management algorithm for hemodialysis patients 
Several anemia guidelines for hemodialysis patients have recommended a target hemoglobin (Hb) range of 10–12 g/dL. However, maintaining Hb values continuously within a narrow target has been difficult, and there has been no generally accepted anemia management algorithm for hemodialysis patients.
In our study, we created an anemia management algorithm that considers the length of erythrocyte lifetimes, focuses on the combination of erythropoiesis-stimulating agent management and iron administration, and prevents iron deficiency and overload. Our algorithm established a target Hb range of 10–12 g/dL.
We evaluated our algorithm in 49 patients for 6 months. The mean Hb values were approximately 11 g/dL during our study period. The percentage of patients in the target Hb range of 10–12 g/dL increased from 77.6% (38 of 49) at baseline to 85.7% (42 of 49) at 4–6 months. Throughout monthly regular blood tests during 1–6 months after we introduced our algorithm, Hb values remained within the target range in 55.1% (27 of 49) of patients. The standard deviation of Hb values significantly decreased at 5 and 6 months (P=0.013 and P=0.047, respectively; 1 g/dL at 0 month, 0.7 g/dL at 5 months, and 0.7 g/dL at 6 months). Our algorithm also succeeded in suppressing cumulative doses of iron (≤800 mg) and decreasing the ferritin values significantly (P=0.011). There were no significant differences in erythropoiesis-stimulating agent doses between 0 and 6 months (P=0.357).
Our anemia management algorithm successfully increased the number of patients in the target Hb range, significantly decreased the Hb standard deviation, suppressed cumulative doses of iron, and decreased ferritin values. These results suggest a better prognosis for hemodialysis patients. Further studies are required to evaluate our algorithm.
PMCID: PMC4484653  PMID: 26150734
erythropoiesis-stimulating agent; hemoglobin; iron; hemoglobin standard deviation; target hemoglobin range; ferritin
2.  Changes in skeletal muscle microcirculation after a hemodialysis session correlates with adequacy of dialysis 
Monitoring of the microcirculation may add additional information in terms of improving the adequacy of hemodialysis (HD) for patients. Withdrawal of liquid and complement activation during a HD session reduces the external pressure on the microcirculation and leads to an increased dilatation of the peripheral capillaries. The purposes of this study were to assess the effect of a single HD or hemodiafiltration session on the thenar microcirculation in patients with end-stage renal disease (ESRD) with or without diabetes, investigate the possible relationship between changes in the microcirculation and adequacy of dialysis (including Kt/V and parameters indicating secondary hyperparathyroidism), and compare microcirculation measurements obtained from patients with ESRD and those from healthy controls.
This pilot prospective observational study including eleven patients with ESRD on maintenance HD (nine men of mean age 73±10.5 years, ten [91%] with hypertension), nine patients with ESRD on maintenance hemodiafiltration (six men of mean age 65.5±13.2 years, five [55.5%] with diabetes and four [44.5%] with hypertension), and eight healthy volunteers. Two paired microcirculation assessments were recorded for each HD patient before and after a dialysis session. Near infrared spectroscopy and the vascular occlusion test were used to assess the microcirculation, and blood work samples were collected before and after dialysis when the pump slowed down.
Patients with ESRD showed an increase in thenar cell metabolism at rest after a 4-hour HD session, and changes in cell metabolism correlated with the Kt/V of the session. Pre-dialysis tissue oxygen saturation over the 4-hour HD session correlated with pre-dialysis serum calcium and parathyroid hormones. Vascular reactivity was lower in ESRD patients receiving HD or hemodiafiltration than in healthy controls.
Improvement in skeletal muscle microcirculation noted after a HD session was related to adequacy of dialysis. Evaluation of the microcirculation may provide additional information for management of patients on HD and identify novel targets for treatment. These preliminary findings need to be tested using a larger data set.
PMCID: PMC4467734  PMID: 26089698
hemodiafiltration; near infrared spectroscopy; end stage renal disease; single-pool Kt/V
3.  Ramadan fasting and chronic kidney disease: does estimated glomerular filtration rate change after and before Ramadan? Insights from a mini meta-analysis 
Ramadan fasting represents one of the five pillars of the Islam creed. Even though patients are exempted from this religious duty, they may be eager to share this particular moment of the year with their family and peers, taking part in the intense spiritual ceremonies and events that characterize this month. However, there are no guidelines or standardized protocols that can help physicians to properly address the issue of patients with chronic kidney disease fasting in Ramadan and correctly advising them. For this purpose, we carried out a systematic review and a meta-analysis to see whether glomerular filtration rate value changed before and after Ramadan. Our main findings are that: chronic kidney disease patients can safely fast during Ramadan since glomerular filtration rate does not change in a statistically significant way and, even though most studies have been carried out during Ramadan falling in cold seasons, the sensitivity analysis did not reveal any impact of seasonality. Further research in the field is needed.
PMCID: PMC4459622  PMID: 26082658
chronic kidney disease; glomerular filtration rate; Ramadan fasting
4.  Decade-long trends (1999–2009) in the characteristics, management, and hospital outcomes of patients hospitalized with acute myocardial infarction with prior diabetes and chronic kidney disease 
Despite the increasing magnitude and impact, there are limited data available on the clinical management and in-hospital outcomes of patients who have diabetes mellitus (DM) and chronic kidney disease (CKD) at the time of hospitalization for acute myocardial infarction (AMI). The objectives of our population-based observational study in residents of central Massachusetts were to describe decade-long trends (1999–2009) in the characteristics, in-hospital management, and hospital outcomes of AMI patients with and without these comorbidities.
We reviewed the medical records of 6,018 persons who were hospitalized for AMI on a biennial basis between 1999 and 2009 at all eleven medical centers in central Massachusetts. Our sample consisted of the following four groups: DM with CKD (n=587), CKD without DM (n=524), DM without CKD (n=1,442), and non-DM/non-CKD (n=3,465).
Diabetic patients with CKD were more likely to have a higher prevalence of previously diagnosed comorbidities, to have developed heart failure acutely, and to have a longer hospital stay compared with non-DM/non-CKD patients. Between 1999 and 2009, there were marked increases in the prescribing of beta-blockers, statins, and aspirin for patients with CKD and DM as compared to those without these comorbidities. In-hospital death rates remained unchanged in patients with DM and CKD, while they declined markedly in patients with CKD without DM (20.2% dying in 1999; 11.3% dying in 2009).
Despite increases in the prescribing of effective cardiac medications, AMI patients with DM and CKD continue to experience high in-hospital death rates.
PMCID: PMC4427079  PMID: 25999755
diabetes; chronic kidney disease; myocardial infarction
5.  Inhibition of RAS in diabetic nephropathy 
Diabetic kidney disease (DKD) is a progressive proteinuric renal disorder in patients with type 1 or type 2 diabetes mellitus. It is a common cause of end-stage kidney disease worldwide, particularly in developed countries. Therapeutic targeting of the renin–angiotensin system (RAS) is the most validated clinical strategy for slowing disease progression. DKD is paradoxically a low systematic renin state with an increased intrarenal RAS activity implicated in its pathogenesis. Angiotensin II (AngII), the main peptide of RAS, is not only a vasoactive peptide but functions as a growth factor, activating interstitial fibroblasts and mesangial and tubular cells, while promoting the synthesis of extracellular matrix proteins. AngII also promotes podocyte injury through increased calcium influx and the generation of reactive oxygen species. Blockade of the RAS using either angiotensin converting enzyme inhibitors, or angiotensin receptor blockers can attenuate progressive glomerulosclerosis in animal models, and slows disease progression in humans with DKD. In this review, we summarize the role of intrarenal RAS activation in the pathogenesis and progression of DKD and the rationale for RAS inhibition in this population.
PMCID: PMC4403683  PMID: 25926752
renin-angiotensin system; diabetic kidney disease; angiotensin II; angiotensin-converting enzyme inhibitors; angiotensin receptor blockers
6.  A fresh look into the pathophysiology of ischemia-induced complications in patients with chronic kidney disease undergoing hemodialysis 
Recent case reports of acute esophageal necrosis in patients with chronic kidney disease (CKD) undergoing hemodialysis encouraged us to look beyond hypoperfusion/ischemia as a sole explanation for this dramatic complication. At least three intriguing pathways, ie, accumulation of protein-bound toxins, endotoxin translocation, and altered mucosal defense mechanisms, have been proposed to explain the inherent susceptibility of CKD patients to developing ischemia-related and cardiovascular events. Interestingly, all the proposed pathways can be potentially antagonized or attenuated. At present, however, it is not known whether one pathway predominates or if any interaction exists between these pathways. More solid experimental and clinical data are warranted to acquire a better insight into the complex pathogenesis of CKD-associated ischemia.
PMCID: PMC4364590  PMID: 25792850
chronic kidney disease; ischemia; pathophysiology; cardiovascular events
7.  Strategies to improve physical activity by exercise training in patients with chronic kidney disease 
Decreased physical activity resulting in muscle loss is often observed in patients with chronic kidney disease and is one of the main predictors of mortality in these patients. Exercise training may improve physical activity and prevent muscle loss in patients with chronic kidney disease. Efforts to introduce exercise training to these patients may be clinically beneficial by reducing their mortality rates.
PMCID: PMC4362894  PMID: 25792851
chronic kidney disease; exercise training; physical activity
8.  Calciphylaxis in end-stage renal disease prior to dialytic treatment: a case report and literature review 
Calciphylaxis is a rare medical condition that is usually diagnosed in patients suffering from end-stage renal disease who are already receiving renal replacement therapy and in those post-transplantation. The pathogenesis still remains to be fully elucidated; hence, the treatment is not uniform. The prognosis is generally poor. The ulcerative stage exhibits a worse prognosis than the nonulcerative one. Calciphylaxis presenting in terminal kidney disease prior to dialytic treatment has only rarely been reported.
Case presentation
A 32-year-old female Caucasian clerk sought medical attention for increasing tiredness and lower limb skin ulcers. Polycystic kidney disease was diagnosed in her late father and two of her siblings. At the first nephrology consultation, obesity, pallor, bilateral flank masses with ballottement, and two ulcers with a dark necrotic center on the distal left leg were noted. In addition, another indurated light bluish lesion of 5 cm just above the right knee with intact skin was observed. All lesions were very tender and warm on touch. Laboratory results yielded hypercalcemia, hyperphosphatemia, anemia, and parathyroid hormone levels that were more than ten times the normal values in the patient, and with a glomerular filtration rate of 4 mL/minute. Skin biopsy confirmed the suspicion of calciphylaxis. The patient was placed on peritoneal dialysis with low Ca concentration baths, cinacalcet, and aluminum hydroxide. The results included correction of hypercalcemia, improvement of phosphate levels, and the product of both Ca and phosphate, but only a transitory decrease in serum parathyroid hormone levels. The ulcerations were completely healed after 2 months of treatment. Cinacalcet was discontinued after 18 months, but multiple large-size, nonulcerative indurated areas appeared 3 months later in the lower limbs after discontinuation of the drug. A parathyroidectomy performed 17 months later revealed a four-gland hyperplastic disease. The patient experienced relief of skin symptoms soon after the procedure and remains in a very satisfactory condition.
Calciphylaxis is a very complex clinical entity. Calciphylaxis presenting prior to dialytic treatment in end-stage renal disease is rare in the absence of a trigger. Cinacalcet and parathyroidectomy should be considered in selected patients.
PMCID: PMC4334332  PMID: 25709494
calciphylaxis; end-stage renal disease; parathyroid hyperplasia; cinacalcet
9.  Low-dose synthetic adrenocorticotropic hormone-analog therapy for nephrotic patients: results from a single-center pilot study 
This report describes our experience using a low-dose synthetic adrenocorticotropic hormone (ACTH) analog for patients affected by nephrotic syndrome who had not responded to or had relapsed after steroid and immunosuppressive treatments.
Patients and methods
Eighteen adult nephrotic patients with an estimated glomerular filtration rate >30 mL/min were recruited. Histological pictures included ten of membranous nephropathy, three of membranous proliferative glomerulonephritis, three of minimal change, and two of focal segmental glomerular sclerosis. All patients received the synthetic ACTH analog tetracosactide 1 mg intramuscularly once a week for 12 months. Estimated glomerular filtration rate, proteinuria, serum lipids, albumin, glucose, and potassium were determined before and during the treatment.
One of the 18 patients discontinued the treatment after 1 month because of severe fluid retention, and two patients were lost at follow-up. Complete remission occurred in six cases, while partial remission occurred in four cases (55.5% responder rate). With respect to baseline, after 12 months proteinuria had decreased from 7.24±0.92 to 2.03±0.65 g/day (P<0.0001), and serum albumin had increased from 2.89±0.14 to 3.66±0.18 g/dL (P<0.0001). Total and low-density lipoprotein cholesterol had decreased from 255±17 to 193±10 mg/dL (P=0.01), and from 168±18 to 114±7 mg/dL (P=0.03), respectively. No cases of severe worsening of renal function, hyperglycemia, or hypokalemia were observed, and no admissions for cardiovascular or infectious events were recorded.
Tetracosactide administration at the dosage of 1 mg intramuscularly per week for 12 months seems to be an acceptable alternative for nephrotic patients unresponsive or relapsing after steroid-immunosuppressive regimens. Further studies should be planned to assess the effect of this low-dose ACTH regimen also in nephrotic patients not eligible for kidney biopsy or immunosuppressive protocols.
PMCID: PMC4327400  PMID: 25709493
ACTH; glomerulonephritis; proteinuria; nephrotic syndrome; CKD; Tetracosactide
10.  Evaluating targets and costs of treatment for secondary hyperparathyroidism in incident dialysis patients: the FARO-2 study 
The aim of this analysis was to estimate biochemical parameters and the costs of treatment of secondary hyperparathyroidism (SHPT) in a subpopulation of the FARO-2 study.
The FARO-2 observational study aimed at evaluating the patterns of treatment for SHPT in naïve hemodialysis patients. Data related to pharmacological treatments and biochemical parameters (parathyroid hormone [PTH], calcium, phosphate) were recorded at entry to hemodialysis (baseline) and 6 months later (second survey). The analysis was performed from the Italian National Health Service perspective.
Two prominent treatment groups were identified, ie, one on oral calcitriol (n=105) and the other on intravenous paricalcitol (n=33); the intravenous calcitriol and intravenous paricalcitol + cinacalcet combination groups were not analyzed due to low patient numbers. At baseline, serum PTH levels were significantly higher in the intravenous paricalcitol group (P<0.0001). At the second survey, the intravenous paricalcitol group showed a higher percentage of patients at target for PTH than in the oral calcitriol group without changing the percentage of patients at target for phosphate. Moreover, between baseline and the second survey, intravenous paricalcitol significantly increased both the percentage of patients at target for PTH (P=0.033) and the percentage of patients at target for the combined endpoint PTH, calcium, and phosphate (P=0.001). The per-patient weekly pharmaceutical costs related to SHPT treatment, erythropoietin-stimulating agents and phosphate binders accounted for 186.32€ and 219.94€ at baseline for oral calcitriol and intravenous paricalcitol, respectively, while after 6 months, the costs were 180.51€ and 198.79€, respectively. Either at the beginning of dialysis or 6 months later, the total cost of SHPT treatment was not significantly lower in the oral calcitriol group compared with the intravenous paricalcitol group, with a difference among groups that decreased by 46% between the two observations. The cost of erythropoietin stimulating agents at the second survey was lower (−22%) in the intravenous paricalcitol group than in the oral calcitriol group (132.13€ versus 168.36€, respectively).
Intravenous paricalcitol significantly increased the percentage of patients at target for the combined endpoint of PTH, calcium, and phosphate (P=0.001). The total cost of treatment for the patients treated with intravenous paricalcitol 6 months after entry to dialysis was not significantly higher than the cost for patients treated with oral calcitriol.
PMCID: PMC4274130  PMID: 25565880
cost consequences analysis; therapeutic costs; outcomes; SHPT treatments; secondary hyperparathyroidism
11.  Drug-induced impairment of renal function 
Pharmaceutical agents provide diagnostic and therapeutic utility that are central to patient care. However, all agents also carry adverse drug effect profiles. While most of these are clinically insignificant, some drugs may cause unacceptable toxicity that impacts negatively on patient morbidity and mortality. Recognizing adverse effects is important for administering appropriate drug doses, instituting preventive strategies, and withdrawing the offending agent due to toxicity. In the present article, we will review those drugs that are associated with impaired renal function. By focusing on pharmaceutical agents that are currently in clinical practice, we will provide an overview of nephrotoxic drugs that a treating physician is most likely to encounter. In doing so, we will summarize risk factors for nephrotoxicity, describe clinical manifestations, and address preventive and treatment strategies.
PMCID: PMC4270362  PMID: 25540591
acute kidney injury; chronic kidney disease; drug nephrotoxicity; chemotherapy; NSAIDs
12.  Evaluating the benefits of home-based peritoneal dialysis 
Peritoneal dialysis (PD) is an effective renal replacement strategy for patients suffering from end-stage renal disease. PD offers patient survival comparable to or better than in-center hemodialysis while preserving residual kidney function, empowering patient autonomy, and reducing financial burden to payors. The majority of patients suffering from kidney failure are eligible for PD. In patients with cardiorenal syndrome and uncontrolled fluid status, PD is of particular benefit, decreasing hospitalization rates and duration. This review discusses the benefits of chronic PD, performed by the patient or a caregiver at home. Recognition of the benefits of PD is a cornerstone in stimulating the use of this treatment strategy.
PMCID: PMC4260684  PMID: 25506238
peritoneal dialysis; survival; quality of life; cost; home dialysis
13.  Necrotizing RPGN with linear anti IgG deposits in a patient with history of granulomatosis with polyangiitis: a case report 
Diagnosing the etiology of a rapidly progressive glomerulonephritis is of vital importance to guide appropriate therapeutic management. This case highlights the complexity involved in establishing diagnosis when presentation is atypical. In certain cases diagnosis cannot be established based on clinical presentation or biopsy findings alone, and critical analysis of biopsy findings in context of clinical presentation is crucial to guide the clinical decision-making process.
Case presentation
A 47-year-old Hispanic male with history of granulomatosis with polyangiitis (GPA) in remission on azathioprine, presented with fatigue and lethargy. Physical examination was unremarkable. Laboratory data revealed elevated creatinine and otherwise normal electrolytes. Urinalysis showed numerous dysmorphic red blood cells with few red cell casts. His serologic results were all negative except anti-proteinase-3 antibody at very low titers. Kidney biopsy showed necrotizing crescentic glomerulonephritis with linear immunoglobulin G staining along the basement membrane.
This case presented conflicting serologic and histopathologic findings. The presence of anti-proteinase-3 antibody supported diagnosis of recurrence of GPA. However, linear staining of immunoglobulin G (IgG) on immunofluorescence (IF) staining of renal biopsy supported anti-glomerular basement membrane (GBM) disease. The treatment of anti-GBM disease and GPA both involve immunosuppression with prednisone and cyclophosphamide. However, patients with anti-GBM disease are also treated with plasmapheresis early in the disease presentation to prevent further damage. The patient with GPA, on the other hand, was shown to benefit from plasmapheresis only in the case of severe renal disease (serum creatinine level more than 5 mg/dL) or pulmonary hemorrhage. In this case, since the patient did not have detectable circulating anti-GBM antibody, the decision was made not to proceed with plasmapheresis. The patient was treated with a standard immunosuppressive regimen consisting of prednisone and cyclophosphamide with partial renal recovery at 2 months.
PMCID: PMC4251529  PMID: 25473306
Necrotizing RPGN; Anti-GBM disease; GPA; ANCA - associated vasculitis; dual antibody-positive disease
14.  Critical care nephrology: could it be a model of multidisciplinarity in ICU nowadays for other sub-specialities – the jury is out 
Emergency and critical care medicine have grown into robust self-supporting disciplines with an increasing demand for dedicated highly-skilled physicians. In the past, “core” specialists were asked to offer bedside advice in acute care wards. In the same regard, critical care medicine and nephrology have been fighting but finally emerged altogether with the concept of critical care nephrology almost 20 years ago. Indeed, polyvalence is no longer a valid option in modern critical care. Uniting forces between disciplines represents the only way to cope with the increasing complexity and cumulating knowledge in the critical care setting. For this reason, the wide array of upcoming acute care sub-specialities must be committed to unrestricted growth and development. This will require competent manpower, a well-designed technical framework, and sufficient financial support. The worldwide success of critical care nephrology proves the feasibility for this concept.
PMCID: PMC4251755  PMID: 25473305
translational medicine; multidisciplinarity; acute medicine; CRRT; dialysis; critical care nephrology
15.  Blood oxygenation level-dependent MRI for assessment of renal oxygenation 
Blood oxygen level-dependent magnetic resonance imaging (BOLD MRI) has recently emerged as an important noninvasive technique to assess intrarenal oxygenation under physiologic and pathophysiologic conditions. Although this tool represents a major addition to our armamentarium of methodologies to investigate the role of hypoxia in the pathogenesis of acute kidney injury and progressive chronic kidney disease, numerous technical limitations confound interpretation of data derived from this approach. BOLD MRI has been utilized to assess intrarenal oxygenation in numerous experimental models of kidney disease and in human subjects with diabetic and nondiabetic chronic kidney disease, acute kidney injury, renal allograft rejection, contrast-associated nephropathy, and obstructive uropathy. However, confidence in conclusions based on data derived from BOLD MRI measurements will require continuing advances and technical refinements in the use of this technique.
PMCID: PMC4247132  PMID: 25473304
kidney; hypoxia; oxygenation; diabetes mellitus; chronic kidney disease; acute kidney injury; contrast-associated nephropathy; BOLD MRI
16.  Quantification and localization of M2 macrophages in human kidneys with acute tubular injury 
This study addresses for the first time the question whether there is significant macrophage population in human kidney sections from patients with acute tubular injury (ATI). We examined therefore the interstitial macrophage population in human kidney tissue with biopsy-proven diagnosis of ATI, minimal change disease (MCD), and MCD with ATI. Kidney biopsies from patients with the above diagnoses were stained with antibodies directed against CD68 (general macrophage marker), CD163 (M2 marker), and HLA-DR (M1 marker) and their respective electron microscopy samples were evaluated for the presence of interstitial macrophages. Our study shows that patients with ATI have significantly increased numbers of interstitial CD68+ macrophages, with an increase in both HLA-DR+ M1 macrophages and CD163+ M2 macrophages as compared to patients with MCD alone. Approximately 75% of macrophages were M2 (CD163+) whereas only 25% were M1 (HLA-DR+). M2 macrophages, which are believed to be critical for wound healing, were found to localize close to the tubular basement membrane of injured proximal tubule cells. Ultra structural examination showed close adherence of macrophages to the basement membrane of injured tubular epithelial cells. We conclude that macrophages accumulate around injured tubules following ATI and exhibit predominantly an M2 phenotype. We further speculate that macrophage-mediated repair may involve physical contact between the M2 macrophage and the injured tubular epithelial cell.
PMCID: PMC4230184  PMID: 25404860
macrophages; acute kidney injury; CD163; HLA-DR; CD68; electron microscopy
17.  Diagnosis and activity assessment of immunoglobulin A nephropathy: current perspectives on noninvasive testing with aberrantly glycosylated immunoglobulin A-related biomarkers 
Immunoglobulin (Ig) A nephropathy (IgAN) is the most common form of glomerular disease worldwide and is associated with a poor prognosis. Thus, development of a curative treatment and strategies for early diagnosis and treatment are urgently needed. Pathological analysis of renal biopsy is the gold standard for the diagnosis and assessment of disease activity; however, immediate and frequent assessment based on biopsy specimens is difficult. Therefore, a simple and safe alternative is desirable. On the other hand, it is now widely accepted that multi-hit steps, including production of aberrantly glycosylated serum IgA1 (first hit), and IgG or IgA autoantibodies that recognize glycan containing epitopes on glycosylated serum IgA1 (second hit) and their subsequent immune complex formation (third hit) and glomerular deposition (fourth hit), are required for continued progression of IgAN. Although the prognostic and predictive values of several markers have been discussed elsewhere, we recently developed a highly sensitive and specific diagnostic method by measuring serum levels of glycosylated serum IgA1 and related IgA immune complex. In addition, we confirmed a significant correlation between serum levels of these essential effector molecules and disease activity after treatment, suggesting that each can be considered as a practical surrogate marker of therapeutic effects in this slowly progressive disease. Such a noninvasive diagnostic and activity assessment method using these disease-oriented specific biomarkers may be useful in the early diagnosis of and intervention in IgAN, with appropriate indication for treatment, and thus aid in the future development and dissemination of specific and curative treatments.
PMCID: PMC4219541  PMID: 25378944
galactose-deficient immunoglobulin A1; anti-glycan antibody; immune complex; N-acetylgalactosamine; surrogate marker
18.  Optimal first-line and second-line treatments for metastatic renal cell carcinoma: current evidence 
Since 2005, an abundance of targeted agents has been approved for the treatment of metastatic renal cell carcinoma (mRCC), without any specification as to what may be the most optimal first-line and second-line sequence. Hence, our objective was to critically examine the evidence supporting the use of first-line and second-line agents in the management of mRCC. Our review suggests that in first line, sunitinib and pazopanib represent treatment options for patients with favorable or intermediate-risk features and clear cell histology. Unfortunately, the Phase III trial cannot conclusively prove the noninferiority of pazopanib relative to sunitinib. Hence, the use of sunitinib as first-line standard of care remains justified. Pazopanib represents an option for specific patients in whom sunitinib might not be tolerated. In patients with poor-risk features, temsirolimus represents the only option supported with level 1 evidence. Less optimal alternatives include sunitinib and bevacizumab combined with interferon, based on the minimal inclusion of poor-risk patients in pivotal Phase III studies of these two molecules. In patients with non-clear cell mRCC, the use of temsirolimus is supported by Phase III data, unlike for any other molecule. In second line, the options consist of everolimus and axitinib. However, the axitinib data are substantially more robust given the inclusion of more patients considered as true second-line, and validly justify the choice of axitinib over everolimus. Nonetheless, the Phase III trial of everolimus may be considered as level 1 evidence for use as third-line or subsequent lines of therapy.
PMCID: PMC4219683  PMID: 25378943
targeted therapy; metastatic; renal cell carcinoma; clear cell; sequential therapy
19.  Optimal management of hyperphosphatemia in end-stage renal disease: an Indian perspective 
There has been an exponential increase in the incidence of diabetes and hypertension in India in the last few decades, with a proportional increase in chronic kidney disease (CKD). Preventive health care and maintenance of asymptomatic chronic disease such as CKD are often neglected by patients until they become symptomatic with fluid retention and uremia. Management of hyperphosphatemia in CKD remains one of the challenges of nephrology in India for this reason, as it is almost completely asymptomatic but contributes to renal osteodystrophy, metastatic vascular calcification, and acceleration of cardiovascular disease. Lack of understanding of the dangers of asymptomatic hyperphosphatemia, the huge pill burden of phosphate binders, difficulty with dietary and dialysis compliance, and most importantly, the added expense of the drugs places additional road blocks in the treatment of hyperphosphatemia at a population level in developing countries like India. In this review we seek to address the contribution of hyperphosphatemia to adverse outcomes and discuss economic, cultural, and societal factors unique to the management of phosphate levels in Indian patients with advanced CKD.
PMCID: PMC4211919  PMID: 25364271
dialysis; chronic kidney disease; vascular calcification
20.  Implantation of peritoneal catheters by laparotomy: nephrologists obtained similar results to general surgeons 
To analyze the complications and costs of minilaparotomies performed by a nephrologist (group A) compared with conventional laparotomies performed by a surgeon (group B) for peritoneal catheter implantation.
Two university hospitals (Santa Sofia and Caldas) in Manizales, Caldas, Colombia.
The study included stage 5 chronic kidney disease patients, with indication of renal replacement therapy, who were candidates for peritoneal dialysis and gave informed consent for a peritoneal catheter implant. Minilaparotomies were performed by a nephrologist in a minor surgery room under local anesthesia. Conventional laparotomies were performed by a surgeon in an operating room under general anesthesia.
Two nephrologists inserted 157 peritoneal catheters, and seven general surgeons inserted 185 peritoneal catheters. The groups had similar characteristics: the mean age was 55 years, 49.5% were men, and the primary diagnoses were diabetic nephropathy, hypertensive nephropathy, and unknown etiology. The implant was successful for 98.09% of group A and 99.46% of group B. There was no procedure-related mortality. The most frequent complications in the first 30 days postsurgery in group A versus group B, respectively, were: peritonitis (6.37% versus 3.78%), exit-site infection (3.82% versus 2.16%), tunnel infection (0% versus 0.54%), catheter entrapment by omentum (1.27% versus 3.24%), peritoneal effluent spillover (1.91% versus 2.16%), draining failure (4.46% versus 6.49%), hematoma (0% versus 1.08%), catheter migration with kinking (3.18% versus 2.70%), hemoperitoneum (1.27% versus 0%), and hollow viscera accidental puncture (1.91% versus 0.54%). There were no statistically significant differences in the number of complications between groups. In 2013, the cost of a surgeon-implanted peritoneal dialysis catheter in Colombia was US $366 (666,000 COP), whereas the cost of a nephrologist-implanted catheter was US $198 (356,725 COP).
Nephrologist-performed minilaparotomies had similar effectiveness to surgeon-performed conventional laparotomies and were cost-effective; however, the nonuse of general anesthesia may be related with hollow viscera puncture during the procedure.
PMCID: PMC4211916  PMID: 25364270
catheter implantation; surgical technique; minilaparotomy; complications
21.  Diabetic nephropathy – complications and treatment 
Diabetic nephropathy is a significant cause of chronic kidney disease and end-stage renal failure globally. Much research has been conducted in both basic science and clinical therapeutics, which has enhanced understanding of the pathophysiology of diabetic nephropathy and expanded the potential therapies available. This review will examine the current concepts of diabetic nephropathy management in the context of some of the basic science and pathophysiology aspects relevant to the approaches taken in novel, investigative treatment strategies.
PMCID: PMC4206379  PMID: 25342915
diabetes; diabetic nephropathy; albuminuria; kidney disease; inflammation
22.  Switch from epoetin to darbepoetin alfa in hemodialysis: dose equivalence and hemoglobin stability 
The objective of the study reported here was to describe dose equivalence and hemoglobin (Hb) stability in a cohort of unselected hemodialysis patients who were switched simultaneously from epoetin alfa to darbepoetin alfa.
This was a multicenter, observational, retrospective study in patients aged ≥18 years who switched from intravenous (IV) epoetin alfa to IV darbepoetin alfa in October 2007 (Month 0) and continued on hemodialysis for at least 24 months. The dose was adjusted to maintain Hb within 1.0 g/dL of baseline.
We included 125 patients (59.7% male, mean [standard deviation (SD)] age 70.4 [13.4] years). No significant changes were observed in Hb levels (mean [SD] 11.9 [1.3] g/dL, 12.0 [1.5], 12.0 [1.5], and 12.0 [1.7] at Months −12, 0, 12 and 24, respectively, P=0.409). After conversion, the erythropoiesis-stimulating agent (ESA) dose decreased significantly (P<0.0001), with an annual mean of 174.7 (88.7) international units (IU)/kg/week for epoetin versus 95.7 (43.4) (first year) and 91.4 (42.7) IU/kg/week (second year) for darbepoetin (65% and 64% reduction, respectively). The ESA resistance index decreased from 15.1 (8.5) IU/kg/week/g/dL with epoetin to 8.1 (3.9) (first year) and 7.9 (4.0) (second year) with darbepoetin (P<0.0001). The conversion rate was 354:1 in patients requiring high (>200 IU/kg/week) doses of epoetin and 291:1 in patients requiring low doses.
In patients on hemodialysis receiving ESAs, conversion from epoetin alfa to darbepoetin alfa was associated with an approximate and persistent reduction of 65% of the required dose. To maintain Hb stability, a conversion rate of 300:1 seems to be appropriate for most patients receiving low doses of epoetin alfa (≤200 IU/kg/week), while 350:1 would be better for patients receiving higher doses.
PMCID: PMC4199978  PMID: 25336984
chronic kidney disease; darbepoetin alfa; dose equivalence; epoetin alfa; hemodialysis; hemoglobin
23.  Challenges of hemodialysis in a new renal care center: call for sustainability and improved outcome 
Nephrologists are faced with enormous challenges in the management of patients with end-stage renal disease, especially in sub-Saharan Africa, where hemodialysis is the most common modality of renal replacement therapy in the region. Therefore, we reviewed our 3 years of experience with hemodialysis services in a tertiary hospital located in a rural community of South West Nigeria. This was with a view to presenting the profile of hemodialysis patients and the challenges they face in sustaining hemodialysis.
We reviewed the case records and hemodialysis registers for 176 patients over the 3 years from November 2010 to December 2013. The data were analyzed using Statistical Package for the Social Sciences version 20 software.
Of the 176 patients, 119 (66.9%) were males. The mean age of the patients was 44.87±17.21 years. Most were semiskilled or unskilled (111; 63.5%) and 29 (16.5%) were students. Twenty-six (14.8%) had acute kidney injury in the failure stage. Chronic glomerulonephritis, hypertensive nephropathy, and diabetic nephropathy accounted for 45.3%, 23.3%, and 12.1%, respectively, of patients with end-stage renal disease. Only 6.8% of patients could afford hemodialysis beyond 3 months.
Sustainability of maintenance hemodialysis is poor in our environment. Efforts should be intensified to improve other modalities of renal replacement therapy, in particular kidney transplantation, which is cost-effective in the long-term. Also, preventive measures such as education for affected patients and the general population would assist in reducing the prevalence and progression to end-stage renal disease.
PMCID: PMC4174020  PMID: 25258555
end-stage renal disease; hemodialysis; sustainability; outcome
24.  The deleterious effects of arteriovenous fistula-creation on the cardiovascular system: a longitudinal magnetic resonance imaging study 
Arteriovenous fistula-formation remains critical for the provision of hemodialysis in end-stage renal failure patients. Its creation results in a significant increase in cardiac output, with resultant alterations in cardiac stroke volume, systemic blood flow, and vascular resistance. The impact of fistula-formation on cardiac and vascular structure and function has not yet been evaluated via “gold standard” imaging techniques in the modern era of end-stage renal failure care.
A total of 24 patients with stage 5 chronic kidney disease undergoing fistula-creation were studied in a single-arm pilot study. Cardiovascular magnetic resonance imaging was undertaken at baseline, and prior to and 6 months following fistula-creation. This gold standard imaging modality was used to evaluate, via standard brachial flow-mediated techniques, cardiac structure and function, aortic distensibility, and endothelial function.
At follow up, left ventricular ejection fraction remained unchanged, while mean cardiac output increased by 25.0% (P<0.0001). Significant increases in left and right ventricular end-systolic volumes (21% [P=0.014] and 18% [P<0.01]), left and right atrial area (11% [P<0.01] and 9% [P<0.01]), and left ventricular mass were observed (12.7% increase) (P<0.01). Endothelial-dependent vasodilation was significantly decreased at follow up (9.0%±9% vs 3.0%±6%) (P=0.01). No significant change in aortic distensibility was identified.
In patients with end-stage renal failure, fistula-formation is associated with an increase in cardiac output, dilation of all cardiac chambers and deterioration in endothelial function.
PMCID: PMC4172192  PMID: 25258554
cardiac; cardiovascular disease; vascular biology
25.  B-type (brain) natriuretic peptide and pruritus in hemodialysis patients 
Introduction and objective
While pruritus is a common complication in hemodialysis patients, the pathophysiological mechanisms remain obscure. Recently, B-type (brain) natriuretic peptide (BNP) has been defined as an itch-selective neuropeptide in pruriceptive neurons in mice, and higher serum levels of BNP are frequently observed in hemodialysis patients. The objective of the present study was to evaluate the role of serum BNP in pruritus in patients undergoing hemodialysis.
Patients and methods
The current cross-sectional study was performed on 43 patients undergoing maintenance hemodialysis. A visual analog scale (VAS) measuring the general severity of pruritus (values from 0 to 10, with higher values indicating more severe pruritus) in daytime and at night was self-reported by patients. Each patient’s background and laboratory tests, including serum BNP in the post-hemodialysis period, were collected. The correlation between VAS and clinical parameters was evaluated.
Both daytime and nighttime VAS scores in diabetic patients were significantly less than those in nondiabetic patients. Multiple regression analysis revealed that pruritus in daytime was worsened by serum BNP (β=2.0, t=2.4, P=0.03), calcium (β=4.4, t=5.2, P<0.0001), and β2-microglobulin (β=2.0, t=3.0, P=0.007), while it was eased by age (β=−2.2, t=−3.2, P=0.0004). Nocturnal pruritus was severe in nondiabetic patients (β=1.7, t=3.8, P=0.0005) and weakened by the total iron binding capacity (β=−2.9, t=−3.1, P=0.004).
It is suggested that a higher level of serum BNP increases the pruritus of hemodialysis patients in daytime and that diabetic patients are less sensitive to itch, especially at nighttime.
PMCID: PMC4149441  PMID: 25187733
B-type brain natriuretic peptide; pruritus; hemodialysis; visual analog scale; itch-selective neuropeptide; pruriceptive neurons; cerebrospinal fluid

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