Chronic Coinfections in Patients Diagnosed with Chronic Lyme Disease: A Systematic Review

PurposeOften, the controversial diagnosis of chronic Lyme disease is given to patients with prolonged, medically unexplained physical symptoms. Many such patients also are treated for chronic coinfections with Babesia, Anaplasma, or Bartonella in the absence of typical presentations, objective clinical findings, or laboratory confirmation of active infection. We have undertaken a systematic review of the literature to evaluate several aspects of this practice.MethodsFive systematic literature searches were performed using Boolean operators and the PubMed search engine.ResultsThe literature searches did not demonstrate convincing evidence of: 1) chronic anaplasmosis infection; 2) treatment-responsive symptomatic chronic babesiosis in immunocompetent persons in the absence of fever, laboratory abnormalities, and detectable parasitemia; 3) either geographically widespread or treatment-responsive symptomatic chronic infection with Babesia duncani in the absence of fever, laboratory abnormalities, and detectable parasitemia; 4) tick-borne transmission of Bartonella species; or 5) simultaneous Lyme disease and Bartonella infection.ConclusionsThe medical literature does not support the diagnosis of chronic, atypical tick-borne coinfections in patients with chronic, nonspecific illnesses.     

Treatment Options for Sexual Dysfunction in Patients with Chronic Kidney Disease: A Systematic Review of Randomized Controlled Trials

Background and objectives: Sexual dysfunction is very common in patients with chronic kidney disease (CKD), but treatment options are limited. The benefits and harms of existing interventions for treatment of sexual dysfunction were assessed in patients with CKD.Design, setting, participants, & measurements: MEDLINE (1966 to December 2008), EMBASE (1980 to December 2008), and the Cochrane Trial Registry (Issue 4 2008) were searched for parallel and crossover randomized and quasi-randomized trials. Treatment effects were summarized as mean differences (MD) or standardized mean difference (SMD) with 95% confidence intervals (CI) using a random effects model.Results: Fourteen trials (328 patients) were included. Phosphodiesterase-5 inhibitors (PDE5i) compared with placebo significantly increased the overall International Index of Erectile Function-5 (IIEF-5) score (three trials, 101 patients, MD 1.81, 95% CI 1.51 to 2.10), all of its individual domains, and the complete 15-item IIEF-5 (two trials, 80 patients, MD 10.64, 95% CI 5.32 to 15.96). End-of-treatment testosterone levels were not significantly increased by addition of zinc to dialysate (two trials, 22 patients, SMD 0.19 ng/dl, 95% CI −2.12 to 2.50), but oral zinc improved end-of-treatment testosterone levels. There was no difference in plasma luteinizing and follicle-stimulating hormone level at the end of the study period with zinc therapy.Conclusions: PDE5i and zinc are promising interventions for treating sexual dysfunction in CKD. Evidence supporting their routine use in CKD patients is limited. There is an unmet need for studying interventions for male and female sexual dysfunction in CKD considering the significant disease burden.Sexual dysfunction is a set of disorders characterized by physical and psychologic changes that result in the inability to perform satisfactory sexual activities. The condition has been found to be significantly more common in men and women with chronic kidney disease (CKD) than in the general population (1). Men with CKD frequently suffer from reduced libido, erectile dysfunction, and difficulty reaching orgasm (2). Approximately 50% of male predialysis CKD patients and 80% of male dialysis patients have erectile dysfunction (3–6). Moreover, the prevalence of erectile dysfunction in male dialysis patients has been found to increase with age (63% <50 years versus 90% ≥50 years) (3). Similar results have been reported in women with CKD, with 55% of female dialysis patients reporting difficulty with sexual arousal (2). Dysmenorrhea, delayed sexual development, impaired vaginal lubrication, dyspareunia, and difficulties in reaching orgasm are also frequently observed (7,8).Multiple factors contribute to the frequent occurrence of sexual dysfunction in CKD patients, including hormonal disturbances (such as hyperprolactinemia, hypogonadism in males, and changes in hypothalamic-pituitary function in women) (9), anemia (10), CKD mineral and bone disorder (4), psychosocial factors (such as depression, anxiety, poor self-esteem, social withdrawal, marital discord, body image issues, fear of disability and death, loss of employment, and financial difficulties) (2,11,12), autonomic neuropathy (13), medications (including antihypertensives, antidepressant, and histamine receptor blockers) (2), and comorbid illness (such as diabetes mellitus, cardiovascular disease, and malnutrition) (2,14). Sexual dysfunction is inversely associated with GFR (7) and is improved after renal transplantation (15,16), suggesting that CKD per se may contribute to sexual dysfunction in these patients (15).Studies have also identified significant associations between sexual dysfunction in CKD patients and depression (8,17), impaired quality of life (8,17,18), and adverse cardiovascular outcomes (19). Effective treatment of sexual dysfunction in CKD patients may therefore potentially lead to improvement in these patient-level outcomes, although a causal link has not been definitively established (18).Therapies that have been used to treat sexual dysfunction include phosphodiesterase-5 inhibitors (PDE5i), intracavernosal injections, intraurethral suppositories, hormonal therapy, mechanical devices, and psychotherapy. Although many clinical trials and reviews have explored the role of these interventions for sexual dysfunction in nonuremic patients (20–24), the effectiveness and safety of these interventions in patients with CKD have not yet been studied thoroughly. Therefore, we aimed to evaluate the benefits and harms associated with various interventions for sexual dysfunction in patients with CKD.     

Weight Loss Interventions in Chronic Kidney Disease: A Systematic Review and Meta-analysis

Background and objectives: Obesity is an independent risk factor for development and progression of chronic kidney disease (CKD). We conducted a systematic review to assess the benefits of intentional weight loss in patients with non–dialysis-dependent CKD and glomerular hyperfiltration.Design, setting, participants, & measurements: We searched MEDLINE, SCOPUS, and conference proceedings for randomized, controlled trials and observational studies that examined various surgical and nonsurgical interventions (diet, exercise, and/or antiobesity agents) in adult patients with CKD. Results were summarized using random-effects model.Results: Thirteen studies were included. In patients with CKD, body mass index (BMI) decreased significantly (weighted mean difference [WMD] −3.67 kg/m²; 95% confidence interval [CI] −6.56 to −0.78) at the end of the study period with nonsurgical interventions. This was associated with a significant decrease in proteinuria (WMD −1.31 g/24 h; 95% CI −2.11 to −0.51) and systolic BP with no further decrease in GFR during a mean follow-up of 7.4 mo. In morbidly obese individuals (BMI >40 kg/m²) with glomerular hyperfiltration (GFR >125 ml/min), surgical interventions decreased BMI, which resulted in a decrease in GFR (WMD −25.56 ml/min; 95% CI −36.23 to −14.89), albuminuria, and systolic BP.Conclusions: In smaller, short-duration studies in patients with CKD, nonsurgical weight loss interventions reduce proteinuria and BP and seem to prevent further decline in renal function. In morbidly obese individuals with glomerular hyperfiltration, surgical interventions normalize GFR and reduce BP and microalbuminuria. Larger, long-term studies to analyze renal outcomes such as development of ESRD are needed.Nearly two thirds of US adults are overweight (body mass index [BMI] ≥25 kg/m²), and of these, one half are obese (BMI ≥30 kg/m²) (1). Obesity not only is associated with an increase in morbidity, mortality, and reduction in life expectancy but also leads to an increase in the incidence of diabetes, hypertension, and dyslipidemia that are independent risk factors for chronic kidney disease (CKD) and coronary artery disease (2–5). Multiple mechanisms by which obesity may initiate and exacerbate CKD exist, and recent observational studies have established obesity as an independent risk factor for CKD and the development of ESRD (6–8).Currently, >20 million Americans have CKD, and the projections for 2015 estimate that there will be >700,000 prevalent cases of ESRD in the United States (9). The health care costs that are associated with this increase are staggering. Diabetes and hypertension together account for >70% of the incident and prevalent cases of ESRD. Given the epidemic of obesity in the United States and around the world, the numbers of obesity-related cases of diabetes, hypertension, and kidney disease are expected to increase. Several treatment options to prevent the progression of CKD have been tested. To date, the major impact on the progression of CKD and the incidence of ESRD has been through the treatment of proteinuria and hypertension (10,11). Although weight loss has been shown to reduce proteinuria in obese patients, the impact on progression of CKD and development of ESRD is less clear (12). Especially, with the increasing number of weight reduction surgeries being performed, intentional weight loss might be a therapeutic option for CKD if its benefits are proved (13,14). Hence, we conducted a systematic review to analyze the impact of weight loss interventions in patients with preexisting CKD and in patients with obesity-related glomerular hyperfiltration.     

Daily Physical Activity in Patients with Chronic Obstructive Pulmonary Disease: A Systematic Review

Patients with chronic obstructive pulmonary disease (COPD) are often limited in their daily physical activity. However, the level, type and intensity of daily physical activity are not known, nor there is a clear insight in the contributing factors. The aim of this review is to describe daily physical activity of COPD patients, and to examine its relationship with demographic factors, pulmonary function, physical fitness, systemic inflammation and quality of life. A systematic literature search was conducted, including studies assessing daily physical activity in all stages of COPD by various different types of measurement techniques. In total, 47 studies were selected; 17 performance-, 20 questionnaire-, and 12 interview-based. Two studies used both a performance- and questionnaire-based method. Overall, COPD patients have a lower level and intensity of daily physical activity compared to healthy controls. This was reported by performance- as well as questionnaire-based studies, yet with a large variation (42–86% and 28–97%, respectively). Reduced daily physical activity is associated with higher levels of airway obstruction, higher levels of systemic inflammation, and lower levels of physical fitness. The association between daily physical activity and quality of life is less clear. In conclusion, this is the first review that examined the level, type and determinants of daily physical activity in COPD. It demonstrates that reduced daily physical activity frequently occurs in COPD patients, yet with a large variation. Methods of measuring and reporting daily physical activity should be more standardized.     

Association Between Hepatitis C Virus and Chronic Kidney Disease: A Systematic Review and Meta-Analysis

Introduction and aim. The role of hepatitis C virus infection as a risk factor for the development and progression of chronic kidney disease in the general population remains unclear.Material and methods. A systematic review of the published medical literature was performed to assess whether positive anti-HCV serologic status is associated with higher frequency of chronic kidney disease in the adult general population. We used a random-effects model to generate a summary estimate of the relative risk of chronic kidney disease (defined by lowered glomerular filtration rate or detectable proteinuria) with HCV across the published studies. Meta-regression and stratified analysis were also carried out.Results. Forty studies were eligible (n = 4,072,867 patients), and separate meta-analyses were conducted according to the outcome. Pooling results of longitudinal studies (n = 15 studies, n = 2,299,134 unique patients) demonstrated an association between positive anti-HCV serologic status and increased incidence of CKD, the summary estimate for adjusted HR with HCV across the surveys, 1.54 (95% CI, 1.26; 1.87) (P < 0.001). Between-study heterogeneity was observed (Q value by Chi-squared [χ²] test 500.3, P < 0.0001). The risk of chronic kidney disease related to HCV, in the subset of surveys from Asia was 1.45 (1.27; 1.65) (P < 0.001) (no heterogeneity). According to our meta-regression, ageing (P < 0.0001) and duration of follow-up (P < 0.0001) increased the risk of chronic kidney disease among HCV-positive subjects. We observed a relationship between anti-HCV positive serologic status and frequency of proteinuria, adjusted effect estimate of proteinuria with HCV among surveys was 1.633 (95% CI, 1,29; 2.05) (P < 0.001) (n = 10 studies; 315,404 unique patients). However, between-studies heterogeneity was noted (P value by Q test < 0.0001).Conclusion. An association between HCV infection and increased risk of chronic kidney disease in the general population exists. The mechanisms underlying such association are currently under active investigation.     

Effect of Elective Coronary Angiography on Glomerular Filtration Rate in Patients with Advanced Chronic Kidney Disease

Background and objectives: Preemptive transplantation is ideal for patients with advanced chronic kidney disease (CKD). The practice has been to perform coronary angiography (CA) on all patients aged >50, all diabetics, and all patients with cardiac symptoms or disease with a view to revascularization before transplantation. Historically patients have delayed CA until established on renal replacement therapy due to concerns of precipitating the need for chronic dialysis. The objectives of this study were to establish the risk of contrast nephropathy in patients with advanced CKD who undergo screening CA, and to determine whether or not preemptive transplantation is achievable.Design and setting: This retrospective analysis included 482 patients with stage IV/V CKD seen in West London predialysis clinics from 2004 to 2007. Seventy-six of 482 (15.8%) patients considered as potential transplant recipients met the authors'' criteria for coronary angiography. Modification of Diet in Renal Disease (MDRD) GFR measurements were recorded for the 12 mo preceding and 12 mo following CA unless a defined endpoint was reached (transplantation, dialysis, or death).Results: Mean MDRD GFR at CA was 12.51 ± 3.51 ml/min. The trend was not significantly different 6 mo pre- and postangiography. Cumulative dialysis-free survival was 89.1% 6 mo postangiography. Twenty-three of 76 (30.3%) patients had flow-limiting coronary artery disease. Twenty-five of 76 (32.9%) patients underwent transplantation with 22 of 25 (88.0%) transplants being performed preemptively.Conclusions: The data suggest CA screening does not accelerate the decline in renal function for patients with advanced CKD, facilitating a safe preemptive transplant program.It is well established that chronic kidney disease (CKD) is associated with premature atherosclerosis and results in an increased risk of cardiovascular morbidity and mortality (1). For patients with CKD, transplantation offers a greater survival advantage over other forms of renal replacement therapy (2). To minimize perioperative cardiac events, and reduce long-term cardiac morbidity, our practice has been to perform coronary angiography with a view to revascularization of significant coronary artery disease (CAD) before transplantation in all potential transplant recipients with one or more of the following criteria: age >50 yr, type 1 or type 2 diabetes, cardiac symptoms or disease irrespective of age, or an abnormal electrocardiogram other than left ventricular hypertrophy. Historically, there has been a tendency to delay coronary angiography in transplant recipients until they have been established on renal replacement therapy due to the concerns that contrast induced nephropathy (CIN) and cholesterol embolization syndrome may precipitate the need for chronic dialysis.The reported incidence of CIN following coronary angiography ranges from 3.3% to 37% (3–5), with pre-existing renal disease being the greatest independent predictor. The severity of renal dysfunction measured by serum creatinine directly correlates with the incidence of CIN (6). The greatest concern for the patient is the need for dialysis treatment in the setting of CIN, which in one study has been reported to occur in 7.1% patients in the short term, and 0.9% in the long term (7). Acute dialysis requirement following percutaneous intervention is associated with a marked increase in hospital mortality (8). The renal dysfunction associated with CIN peaks at 3 to 5 d following the administration of contrast and improves in 1 to 3 wk (9). In those patients in whom renal insufficiency persists >3 wk, cholesterol embolization syndrome may be a contributory factor.It is possible that the safety profile of coronary angiography has improved in the modern era, with the use of adequate hydration, N-Acetylcysteine, smaller volumes of nonionic contrasts, biplane imaging techniques, staged procedures in cases requiring intervention, and careful postangiography monitoring (10). If this is the case, potential transplant recipients should not be put off coronary angiography until established on renal replacement therapy, as this only heightens their cardiovascular burden, which may be halted or slowed down by successful kidney transplantation (11).The purpose of this study was to establish the risk of contrast nephropathy to patients with advanced CKD (stages IV or V) who undergo elective and timely screening coronary angiography, and to determine whether or not preemptive transplantation is achievable.     

Comparison of Coronary Artery Bypass Grafting and Drug-Eluting Stents in Patients with Left Main Coronary Artery Disease and Chronic Kidney Disease: A Systematic Review and Meta-Analysis

BackgroundTreatment of left main coronary artery disease (LMCAD) in patients with chronic kidney disease (CKD) with either percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) remains controversial. Therefore, we performed a meta-analysis to evaluate the optimal choice of therapy when treating LMCAD in patients with CKD.MethodWe performed an electronic database search of Pubmed, Embase, and Cochrane Library for all studies that compared PCI with CABG when treating LMCAD in the setting of CKD. Major adverse cardiac and cerebrovascular events (MACCE) were the primary outcome. Secondary outcomes included myocardial infarction (MI), cerebrovascular events, all-cause mortality, and repeat revascularization.ResultsOur analysis included 5 studies (2 randomized controlled trial and 3 retrospective) representing a total of 1212 patients. Mean follow up was 3.4 ± 1.3 years. Our study demonstrated a significant reduction in MACCE for patients treated with CABG compared with PCI (odd ratio [OR] 0.72; 95% confidence interval [CI] 0.55–0.95, P = 0.02, I² = 0%). We also found a significant reduction in both MI (OR 0.55; 95% CI 0.34–0.87; P = 0.01; I² = 0%) and repeat revascularization (OR 0.22; 95% CI 0.10–0.51; P < 0.001, I² = 63%) in the CABG group. However, CABG was associated with increased risks of cerebrovascular disease events compared with PCI (OR 2.04; 95% CI 1.02–4.08; P = 0.04, I² = 0%).ConclusionIn patients with CKD requiring LMCAD intervention, CABG is associated with a lower risk of MACCE, MI, and repeat revascularization, however it was associated with an increased risk of cerebrovascular accidents when compared to patients who received PCI therapy. Further RCTs with sufficient power are required to confirm these findings.     

Revascularization Options in Patients with Chronic Kidney Disease

Cardiovascular disease is the leading cause of death in patients who have chronic kidney disease or end-stage renal disease and are undergoing hemodialysis. Chronic kidney disease is a recognized risk factor for premature atherosclerosis. Unfortunately, most major randomized clinical trials that form the basis for evidence-based use of revascularization procedures exclude patients who have renal insufficiency. Retrospective, observational studies suggest that patients with end-stage renal disease and severe coronary occlusive disease have a lower risk of death if they undergo coronary revascularization rather than medical therapy alone. Due to a lack of prospective studies, however, the relative merits of percutaneous versus surgical revascularization are merely a matter of opinion. Several small, retrospective studies have shown that coronary artery bypass grafting is associated with higher procedural death but better long-term survival than is percutaneous coronary intervention. This difference appears to result from poor long-term results of percutaneous coronary intervention in patients who have chronic kidney disease or end-stage renal disease.Because randomized trials comparing percutaneous coronary intervention and coronary artery bypass grafting have included patients undergoing balloon angioplasty and placement of bare-metal stents, their conclusions are suspect in the era of drug-eluting stents. In this review, we discuss different revascularization options for patients with chronic kidney disease, the outcomes of revascularization procedures, and the risk factors for adverse outcomes.Key words: Angioplasty, transluminal, percutanous coronary; coronary artery bypass; coronary artery bypass, off-pump; creatinine/blood/metabolism; drug-eluting stents; extracorporeal circulation; glomerular filtration rate; kidney failure, chronic; renal dialysis; stents; treatment outcomeThe prevalence of end-stage renal disease (ESRD), defined as renal dysfunction requiring chronic renal replacement therapy, is increasing. In 2007, there were about 341,000 patients with ESRD on hemodialysis and 143,000 patients with transplanted kidneys in the United States.¹ An additional 8% of adults in the U.S. have chronic kidney disease stages 3 and 4 (characterized by a glomerular filtration rate [GFR] between 15 and 60 mL/min/1.73 m²).² The United States Renal Data System (USRDS) projects that, at the current growth rate, the number of patients with ESRD will increase to 534,000 by the year 2020.¹ Within 18 to 24 months of beginning renal replacement therapy, 12% of patients will have an acute myocardial infarction, more than 60% will receive a diagnosis of congestive heart failure, and, by 3 years, 38% will die suddenly, presumably of cardiovascular causes.¹ In chronic kidney disease patients who are not hemodialysis dependent, the risk of dying of cardiovascular disease is greater than the risk of developing ESRD.³ In addition to the traditional risk factors for atherosclerosis,⁴ an abnormal GFR contributes independently to the risk of atherosclerosis-related events in patients with kidney disease.⁵     

Hypertension Management in Patients with Chronic Kidney Disease

Hypertension and chronic kidney disease are closely linked. Patients with chronic kidney disease have hypertension almost universally and uncontrolled hypertension accelerates the decline in kidney function. The pathophysiology of hypertension in chronic kidney disease is complex, but is largely related to reduced nephron mass, sympathetic nervous system overactivation, involvement of the renin-angiotensin-aldosterone system, and generalized endothelial dysfunction. Consensus guidelines for blood pressure targets have adopted a blood pressure <120/80 mm Hg in native chronic kidney disease and <130/80 mm Hg in kidney transplant recipients. Guidelines also strongly advocate for renin-angiotensin-aldosterone system blockade as the first-line therapy.     

Representation of Chronic Kidney Disease in Randomized Controlled Trials Among Patients With Heart failure With Reduced Ejection Fraction: A Systematic Review

Patients with advanced chronic kidney disease (CKD) have largely been excluded from randomized control trials (RCTs) in heart failure (HF). This creates a paucity of high quality evidence for guideline directed medical therapy (GDMT), particularly in patients with heart failure with reduced ejection fraction (HFrEF) and CKD. This is a systematic review looking at the patterns and rates of inclusion of CKD in RCTs among patients with HFrEF. The search included RCTs from January 2010 to December 2020. A heat map was constructed to reflect the stages of CKD stages. The percentage of studies that included advanced CKD (stages IV-V) was recorded and log transformed, and then fitted into a time regression model. A P value of <0.05 was considered statistically significant. Out of the 3052 screened, 706 studies were included in the analysis. Only 61% of the RCTs reported at least some information on kidney function. There was a trend of increase in percentage of studies that included CKD stages IV-V from years 2010 to 2020. This was confirmed with a statistically significant linear trend P = 0.02 while the percentage of studies that included dialysis and kidney transplant recipients remained consistently low. There is a paucity of high-quality evidence for GDMT in the HFrEF population with CKD, particularly in those with advanced non-dialytic CKD, those on maintenance dialysis and kidney transplant recipients. There is a pressing need for wider inclusion of patients with advanced CKD in RCTs of GDMT in HFrEF.     

Metabolic Syndrome and Kidney Disease: A Systematic Review and Meta-analysis

Summary

Background and objectives

Observational studies have reported an association between metabolic syndrome (MetS) and microalbuminuria or proteinuria and chronic kidney disease (CKD) with varying risk estimates. We aimed to systematically review the association between MetS, its components, and development of microalbuminuria or proteinuria and CKD.

Design, setting, participants and measurements and population

We searched MEDLINE (1966 to October 2010), SCOPUS, and the Web of Science for prospective cohort confidence interval (CI) studies that reported the development of microalbuminuria or proteinuria and/or CKD in participants with MetS. Risk estimates for eGFR <60 ml/min per 1.73 m² were extracted from individual studies and pooled using a random effects model. The results for proteinuria outcomes were not pooled because of the small number of studies.

Results

Eleven studies (n = 30,146) were included. MetS was significantly associated with the development of eGFR <60 ml/min per 1.73 m² (odds ratio, 1.55; 95% CI, 1.34, 1.80). The strength of this association seemed to increase as the number of components of MetS increased (trend P value = 0.02). In patients with MetS, the odds ratios (95% CI) for development of eGFR <60 ml/min per 1.73 m² for individual components of MetS were: elevated blood pressure 1.61 (1.29, 2.01), elevated triglycerides 1.27 (1.11, 1.46), low HDL cholesterol 1.23 (1.12, 1.36), abdominal obesity 1.19 (1.05, 1.34), and impaired fasting glucose 1.14 (1.03, 1.26). Three studies reported an increased risk for development of microalbuminuria or overt proteinuria with MetS.

Conclusions

MetS and its components are associated with the development of eGFR <60 ml/min per 1.73 m² and microalbuminuria or overt proteinuria.