Treatment of atherosclerotic renovascular hypertension: review of observational studies and a meta-analysis of randomized clinical trials

Nephrology Dialysis Transplantation - current issue Treatment of atherosclerotic renovascular hypertension: review of observational studies and a meta-analysis of randomized clinical trials

Atherosclerotic renal artery stenosis can cause ischaemic nephropathy and arterial hypertension. We herein review the observational and randomized clinical trials (RCTs) comparing medical and endovascular treatment for control of hypertension and renal function preservation. Using the Population Intervention Comparison Outcome (PICO) strategy, we identified the relevant studies and performed a novel meta-analysis of all RCTs to determine the efficacy and safety of endovascular treatment when compared with medical therapy. The following outcomes were examined: baseline follow-up difference in mean systolic and diastolic blood pressure (BP), serum creatinine, number of drugs at follow-up, incident events (heart failure, stroke, and worsening renal function), mortality, cumulative relative risk of heart failure, stroke, and worsening renal function. Seven studies comprising a total of 2155 patients (1741 available at follow-up) were considered, including the recently reported CORAL Study. Compared with baseline, diastolic BP fell more at follow-up in patients in the endovascular than in the medical treatment arm (standard difference in means –0.21, 95% confidence interval (CI): –0.342 to –0.078, P = 0.002) despite a greater reduction in the mean number of antihypertensive drugs (standard difference in means –0.201, 95% CI: –0.302 to –0.1, P < 0.001). At variance, follow-up changes (from baseline) of systolic BP, serum creatinine, and incident cardiovascular event rates did not differ between treatment arms. Thus, patients with atherosclerotic renal artery stenosis receiving endovascular treatment required less anti-antihypertensive drugs at follow-up than those medically treated. Notwithstanding this, they evidenced a better control of diastolic BP.

http://ndt.oxfordjournals.org/cgi/content/short/30/4/541?rss=1

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Alberto Reino Buelvas 

Médico Internista Nefrólogo

Dose-Finding Study of Rivaroxaban in Hemodialysis Patients

American Journal of Kidney Diseases Dose-Finding Study of Rivaroxaban in Hemodialysis Patients

Use of vitamin K antagonists for the prevention of stroke and systemic embolism in dialysis patients with nonvalvular atrial fibrillation is controversial. However, no good alternatives presently are available. The anti−factor Xa antagonist rivaroxaban is contraindicated for lack of pharmacokinetic, pharmacodynamic, and clinical data. This study aims to characterize the pharmacokinetics/pharmacodynamics of rivaroxaban in maintenance hemodialysis patients.


http://www.ajkd.org/article/S0272-6386(15)00490-4/abstract?rss=yes

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Alberto Reino Buelvas 

Médico Internista Nefrólogo

Amikacin Prophylaxis and Risk Factors for Surgical Site Infection After Kidney Transplantation

Transplantation - Current Issue Amikacin Prophylaxis and Risk Factors for Surgical Site Infection After Kidney Transplantation

Background: Antibiotic prophylaxis plays a major role in preventing surgical site infections (SSIs). This study aimed to evaluate antibiotic prophylaxis in kidney transplantation and identify risk factors for SSIs. Methods: We evaluated all kidney transplantation recipients from January 2009 and December 2012. We excluded patients who died within the first 72 hr after transplantation, were undergoing simultaneous transplantation of another organ, or were below 12 years of age. The main outcome measure was SSI during the first 60 days after transplantation. Results: A total of 819 kidney transplants recipients were evaluated, 65% of whom received a deceased-donor kidney. The antibiotics used as prophylaxis included cephalosporin, in 576 (70%) cases, and amikacin, in 233 (28%). We identified SSIs in 106 cases (13%), the causative agent being identified in 72 (68%). Among the isolated bacteria, infections caused by extended-spectrum β-lactamase–producing Enterobacteriaceae predominated. Multivariate analysis revealed that the risk factors for post-kidney transplantation SSIs were deceased donor, thin ureters at kidney transplantation, antithymocyte globulin induction therapy, blood transfusion at the transplantation procedure, high body mass index, and diabetes mellitus. The only factor associated with a reduction in the incidence of SSIs was amikacin use as antibiotic prophylaxis. Factors associated with reduced graft survival were: intraoperative blood transfusions, reoperation, human leukocyte antigen mismatch, use of nonstandard immunosuppression therapy, deceased donor, post-kidney transplantation SSIs, and delayed graft function. Conclusion: Amikacin prophylaxis is a useful strategy for preventing SSIs.


http://journals.lww.com/transplantjournal/Fulltext/2015/03000/Amikacin_Prophylaxis_and_Risk_Factors_for_Surgical.14.aspx

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Alberto Reino Buelvas 

Médico Internista Nefrólogo

Noroviruses as a Cause of Diarrhea in Immunocompromised Pediatric Hematopoietic Stem Cell and Solid Organ Transplant Recipients

AJT - Early Noroviruses as a Cause of Diarrhea in Immunocompromised Pediatric Hematopoietic Stem Cell and Solid Organ Transplant Recipients

Case reports describe significant norovirus gastroenteritis morbidity in immunocompromised patients. We evaluated norovirus pathogenesis in prospectively enrolled solid organ (SOT) and hematopoietic stem cell transplant (HSCT) patients with diarrhea who presented to Texas Children's Hospital and submitted stool for enteric testing. Noroviruses were detected by real-time reverse transcription polymerase chain reaction. Clinical outcomes of norovirus diarrhea and non-norovirus diarrhea patients, matched by transplanted organ type, were compared. Norovirus infection was identified in 25 (22%) of 116 patients, more frequently than other enteropathogens. Fifty percent of norovirus patients experienced diarrhea lasting ≥14 days, with median duration of 12.5 days (range 1–324 days); 29% developed diarrhea recurrence. Fifty-five percent of norovirus patients were hospitalized for diarrhea, with 27% requiring intensive care unit (ICU) admission. One HSCT recipient developed pneumatosis intestinalis. Three HSCT patients expired ≤6 months of norovirus diarrhea onset. Compared to non-norovirus diarrhea patients, norovirus patients experienced significantly more frequent ICU admission (27% vs. 0%, p = 0.02), greater serum creatinine rise (median 0.3 vs. 0.2 mg/dL, p = 0.01), and more weight loss (median 1.6 vs. 0.6 kg, p < 0.01). Noroviruses are an important cause of diarrhea in pediatric transplant patients and are associated with significant clinical complications.

http://onlinelibrary.wiley.com/resolve/doi?DOI=10.1111%2Fajt.13227

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Alberto Reino Buelvas 

Médico Internista Nefrólogo

Limitations of Hemoglobin A1c for the Diagnosis of Posttransplant Diabetes Mellitus

Transplantation - Current Issue Limitations of Hemoglobin A1c for the Diagnosis of Posttransplant Diabetes Mellitus

Background: Posttransplant diabetes mellitus (PTDM) is usually detected 2 to 3 months after transplantation by fasting plasma glucose (fPG) ≥7.0 mmol/L (≥126 mg/dL) and/or 2 hr post-challenge plasma glucose ≥11.1 mmol/L (≥200 mg/dL) during an oral glucose tolerance test (OGTT). Recently, glycosylated hemoglobin (HbA1c) of 6.5% or higher (≥47.5 mmol/mol) has been proposed as an alternative diagnostic criterion (the HbA1c criterion). We aimed to assess the sensitivity of applying the HbA1c criterion alone or in combination with a single measurement of fPG of 7.0 mmol/L or higher (≥126 mg/dL) at 10 weeks after transplantation as screening tests for the diagnosis of PTDM. Methods: From 1999 to 2011, measurements of fPG, HbA1c, and OGTT were performed in 1,619 nondiabetic renal transplant recipients. Results: The HbA1c criterion detected 38.0% of patients with PTDM diagnosed with the standard diagnostic criteria. The specificity was 86.3%. When the HbA1c threshold value was lowered to 6.2% (44.3 mmol/mol), sensitivity increased to 57.8% with a corresponding reduced specificity of 80.4%. A combination of the HbA1c criterion and fPG of 7.0 mmol/L or higher (126 mg/dL) at 10 weeks after transplantation improved diagnostic precision with a sensitivity of 77.7% and a specificity of 96.1%. Conclusion: The proposed diagnostic HbA1c criterion failed to detect most cases of PTDM, and one of four cases of PTDM was detected by OGTT alone. This indicates that the HbA1c threshold value likely needs to be lowered for renal transplant recipients and supports continued use of OGTT as a diagnostic tool for detection of PTDM.


http://journals.lww.com/transplantjournal/Fulltext/2015/03000/Limitations_of_Hemoglobin_A1c_for_the_Diagnosis_of.29.aspx

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Alberto Reino Buelvas 

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Dobutamine Stress Cardiac MRI for Assessment of Coronary Artery Disease Prior to Kidney Transplantation

American Journal of Kidney Diseases Dobutamine Stress Cardiac MRI for Assessment of Coronary Artery Disease Prior to Kidney Transplantation

Cardiovascular disease is the leading cause of death in end-stage kidney disease following successful kidney transplantation.1 The accuracy of noninvasive cardiac stress testing versus coronary angiography in detecting significant coronary artery disease (CAD) prior to kidney transplantation is inadequate.2-4 Dobutamine stress cardiac magnetic resonance (DSCMR) imaging offers highly accurate, prognostically relevant results in detecting inducible myocardial ischemia.5,6 We performed a diagnostic test study to evaluate the utility of DSCMR for identifying significant CAD prior to potential kidney transplantation, using angiography as the reference test.


http://www.ajkd.org/article/S0272-6386(15)00423-0/abstract?rss=yes

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Alberto Reino Buelvas 

Médico Internista Nefrólogo

Current Status of Bicarbonate in CKD

Journal of the American Society of Nephrology current issue Current Status of Bicarbonate in CKD

Metabolic acidosis was one of the earliest complications to be recognized and explained pathologically in patients with CKD. Despite the accumulated evidence of deleterious effects of acidosis, treatment of acidosis has been tested very little, especially with respect to standard clinical outcomes. On the basis of fundamental research and small alkali supplementation trials, correcting metabolic acidosis has a strikingly broad array of potential benefits. This review summarizes the published evidence on the association between serum bicarbonate and clinical outcomes. We discuss the role of alkali supplementation in CKD as it relates to retarding kidney disease progression, improving metabolic and musculoskeletal complications.

http://jasn.asnjournals.org/cgi/content/short/26/3/515?rss=1

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Alberto Reino Buelvas 

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Comparison of alemtuzumab versus antithymocyte globulin induction therapy in primary non-sensitized renal transplant patients treated with rapid steroid withdrawal

Clinical Transplantation Comparison of alemtuzumab versus antithymocyte globulin induction therapy in primary non-sensitized renal transplant patients treated with rapid steroid withdrawal

Abstract

Alemtuzumab and rabbit antithymocyte globulin (rATG) are commonly used for induction therapy in renal transplantation. This retrospective, single-center, cohort study evaluated cumulative incidence of 1-year biopsy-proven acute rejection (BPAR) among 200 consecutive primary non-sensitized kidney transplant recipients who received either alemtuzumab (n=100) or rATG (n=100) induction followed by rapid steroid taper, tacrolimus and mycophenolate mofetil (MMF). Protocol biopsies, plasma and urine BK virus PCR, serum creatinine and iothalamate GFR (iGFR) were obtained at 1, 4 and 12 months from transplantation. The 1-year BPAR rates were similar between the alemtuzumab and rATG groups; however, rejection Banff IA and higher was more common in the alemtuzumab arm (18% vs. 5%, P=0.047). After adjusting for confounding variables, alemtuzumab was still associated with Banff IA and higher rejection (adjusted OR: 3.7, CI: 1.2-10.5, P=0.02). Despite similar rates of BK viremia, more patients in the alemtuzumab arm developed BK nephropathy (16% vs. 3%, P=0.046). 1-year iGFR (53.4 ± 20.2 vs. 71.9 ± 27.2 ml/min/1.73 m², P=0.002) and 3-year graft survival (89.5% vs. 95%, P=0.05) were lower in the alemtuzumab group. In low immunological risk kidney transplant recipients on steroid free immunosuppression, alemtuzumab was associated with more severe rejection and BK nephropathy compared to rATG.

This article is protected by copyright. All rights reserved.

http://onlinelibrary.wiley.com/resolve/doi?DOI=10.1111%2Fctr.12532

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Alberto Reino Buelvas 

Médico Internista Nefrólogo

Positive Crossmatch Kidney Transplant Recipients Treated With Eculizumab: Outcomes Beyond 1 Year

AJT - Early Positive Crossmatch Kidney Transplant Recipients Treated With Eculizumab: Outcomes Beyond 1 Year

This study examined outcomes beyond 1 year in eculizumab-treated (EC) positive crossmatch kidney transplants (+XMKTx) compared to a historical control group. +XMKTx received desensitization with either plasma exchange (PE) alone (N = 48) or PE and EC (N = 30). EC, given for at least 1 month, was continued in the setting of persistently high DSA (B flow cytometric crossmatch [BFXM] >200) including: 4 weeks (n = 14); 9 weeks (n = 6), 6 months (n = 2), and 12 months (n = 8). All patients had at least 2 years follow-up. The incidence of acute clinical ABMR was lower in the EC group than controls (6.7% vs. 43.8% p < 0.01). Death-censored allograft survival was similar between groups. Chronic ABMR was the main cause of graft loss. On 1-year protocol biopsies, no differences were noted between EC and controls including: cg score >0, 26.7% versus 31.9% (p = 0.62), ptc score ≥ 2, 60.0% versus 60.0% (p = 1.00), or C4d + , 33.8% versus 13.5% (p = 0.08). A persistently high BFXM in EC-treated patients was associated with cg score >0 at 1 year, while EC appeared to protect against cg if the BFXM remained low. We conclude that despite decreasing acute clinical ABMR rates, EC treatment does not prevent chronic ABMR in recipients with persistently high BFXM after +XMKTx.

http://onlinelibrary.wiley.com/resolve/doi?DOI=10.1111%2Fajt.13168

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Alberto Reino Buelvas 

Médico Internista Nefrólogo

Daclizumab Versus Rabbit Antithymocyte Globulin in High-Risk Renal Transplants: Five-Year Follow-up of a Randomized Study.

AJT Daclizumab Versus Rabbit Antithymocyte Globulin in High-Risk Renal Transplants: Five-Year Follow-up of a Randomized Study.

• Hellemans R, Hazzan M, Durand D, et al. 
• Daclizumab Versus Rabbit Antithymocyte Globulin in High-Risk Renal Transplants: Five-Year Follow-up of a Randomized Study. [JOURNAL ARTICLE]
• Am J Transplant 2015 Feb 23.

We previously reported a randomized controlled trial in which 227 de novo deceased-donor kidney transplant recipients were randomized to rabbit antithymocyte (rATG, Thymoglobulin) or daclizumab if they were considered to be at high immunological risk, defined as high panel reactive antibodies (PRA), loss of a first kidney graft through rejection within 2 years of transplantation, or third or fourth transplantation. Patients treated with rATG had lower incidences of biopsy-proven acute rejection (BPAR) and steroid-resistant rejection at 1 year. Patients were followed to 5 years posttransplant in an observational study; findings are described here. Treatment with rATG was associated with a lower rate of BPAR at 5 years (14.2% vs. 26.0% with daclizumab; p = 0.035). Only one rATG-treated patient (0.9%) and one daclizumab-treated patient (1.0%) developed BPAR after 1 year. Five-year graft and patient survival rates, and renal function, were similar between the two groups. Overall graft survival at 5 years was significantly higher in patients without BPAR (81.0% vs. 54.8%; p < 0.001). In conclusion, rATG is superior to daclizumab for the prevention of BPAR among high-immunological-risk renal transplant recipients. Overall graft survival at 5 years was approximately 70% with either induction therapy, which compares favorably to low-risk cohorts.

http://www.unboundmedicine.com/medline/citation/25707875/Daclizumab_Versus_Rabbit_Antithymocyte_Globulin_in_High_Risk_Renal_Transplants:_Five_Year_Follow_up_of_a_Randomized_Study_

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Alberto Reino Buelvas 

Médico Internista Nefrólogo

Rotavirus in Organ Transplantation: Drug-Virus-Host Interactions

AJT - Early Rotavirus in Organ Transplantation: Drug-Virus-Host Interactions

Although rotavirus is usually recognized as the most common etiology of diarrhea in young children, it can in fact cause severe diseases in organ transplantation recipients irrespective of pediatric or adult patients. This comprehensive literature analysis revealed 200 cases of rotavirus infection with 8 related deaths in the setting of organ transplantation been recorded. Based on published cohort studies, an average incidence of 3% (187 infections out of 6176 organ recipients) was estimated. Rotavirus infection often causes severe gastroenteritis complications and occasionally contributes to acute cellular rejection in these patients. Immunosuppressive agents, universally used after organ transplantation to prevent organ rejection, conceivably play an important role in such a severe pathogenesis. Interestingly, rotavirus can in turn affect the absorption and metabolism of particular immunosuppressive medications via several distinct mechanisms. Even though rotaviral enteritis is self-limiting in general, infected transplantation patients are usually treated with intensive care, rehydration and replacement of nutrition, as well as applying preventive strategies. This article aims to properly assess the clinical impact of rotavirus infection in the setting of organ transplantation and to disseminate the interactions among the virus, host and immunosuppressive medications.

http://onlinelibrary.wiley.com/resolve/doi?DOI=10.1111%2Fajt.13135

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Alberto Reino Buelvas 

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Complement Inhibition in HLA-Incompatible Kidney Transplants: Persisting Antibody-Mediated Injury Despite Marked Decrease of Clinical ABMR.

AJT Complement Inhibition in HLA-Incompatible Kidney Transplants: Persisting Antibody-Mediated Injury Despite Marked Decrease of Clinical ABMR.

• Loupy A, Viglietti D, Mengel M 
• Complement Inhibition in HLA-Incompatible Kidney Transplants: Persisting Antibody-Mediated Injury Despite Marked Decrease of Clinical ABMR. [EDITORIAL]
• Am J Transplant 2015 Mar 2.

http://www.unboundmedicine.com/medline/citation/25731892/Complement_Inhibition_in_HLA_Incompatible_Kidney_Transplants:_Persisting_Antibody_Mediated_Injury_Despite_Marked_Decrease_of_Clinical_ABMR_

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Alberto Reino Buelvas 

Médico Internista Nefrólogo

Positive Crossmatch Kidney Transplant Recipients Treated With Eculizumab: Outcomes Beyond 1 Year.

AJT Positive Crossmatch Kidney Transplant Recipients Treated With Eculizumab: Outcomes Beyond 1 Year.

• Cornell LD, Schinstock CA, Gandhi MJ, et al. 
• Positive Crossmatch Kidney Transplant Recipients Treated With Eculizumab: Outcomes Beyond 1 Year. [JOURNAL ARTICLE]
• Am J Transplant 2015 Mar 2.

This study examined outcomes beyond 1 year in eculizumab-treated (EC) positive crossmatch kidney transplants (+XMKTx) compared to a historical control group. +XMKTx received desensitization with either plasma exchange (PE) alone (N = 48) or PE and EC (N = 30). EC, given for at least 1 month, was continued in the setting of persistently high DSA (B flow cytometric crossmatch [BFXM] >200) including: 4 weeks (n = 14); 9 weeks (n = 6), 6 months (n = 2), and 12 months (n = 8). All patients had at least 2 years follow-up. The incidence of acute clinical ABMR was lower in the EC group than controls (6.7% vs. 43.8% p < 0.01). Death-censored allograft survival was similar between groups. Chronic ABMR was the main cause of graft loss. On 1-year protocol biopsies, no differences were noted between EC and controls including: cg score >0, 26.7% versus 31.9% (p = 0.62), ptc score ≥ 2, 60.0% versus 60.0% (p = 1.00), or C4d + , 33.8% versus 13.5% (p = 0.08). A persistently high BFXM in EC-treated patients was associated with cg score >0 at 1 year, while EC appeared to protect against cg if the BFXM remained low. We conclude that despite decreasing acute clinical ABMR rates, EC treatment does not prevent chronic ABMR in recipients with persistently high BFXM after +XMKTx.

http://www.unboundmedicine.com/medline/citation/25731800/Positive_Crossmatch_Kidney_Transplant_Recipients_Treated_With_Eculizumab:_Outcomes_Beyond_1_Year_

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Alberto Reino Buelvas 

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