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BACKGROUND: Hyperkalemia (HK) is frequently present in chronic kidney disease (CKD). Risk factors for HK among CKD patients include comorbidities and renin-angiotensin-aldosterone system inhibitor (RAASi) treatment. Current standard of care (SoC) often necessitates RAASi down-titration or discontinuation, resulting in poorer cardiorenal outcomes, hospitalization and mortality. This study evaluates the cost-effectiveness of patiromer for HK in CKD patients with and without heart failure (HF) in an Italian setting. METHODS: A lifetime Markov cohort model was developed based on OPAL-HK to assess the health economic impact of patiromer therapy in comparison to SoC after accounting for the effects of HK and RAASi use on clinical events. Outcomes included accumulated clinical events, number needed to treat (NNT) and the incremental cost-effectiveness ratio (ICER). Subgroup analysis was conducted in CKD patients with and without HF. RESULTS: Patiromer was associated with an incremental discounted cost of 4,660 and 0.194 quality adjusted life years (QALYs), yielding an ICER of 24,004. Per 1000 patients, patiromer treatment prevented 275 moderate/severe HK events, 54 major adverse cardiovascular event, 246 RAASi discontinuation and 213 RAASi up-titration/restart. Subgroup analysis showed patiromer was more effective in preventing clinical events in CKD patients with HF compared to those without; QALY gains were greater in CKD patients without HF versus those with HF (0.267 versus 0.092, respectively). Scenario analysis and sensitivity analysis results support base-case conclusions. CONCLUSION: Patiromer is associated with QALY gains in CKD patients with and without HF compared to SoC in Italy. Patiromer prevented HK events, enabled RAASi therapy maintenance and reduced cardiovascular event risk.
ABSTRACT
RATIONALE & OBJECTIVE: Ambulatory blood pressure (BP) monitoring allows concurrent evaluation of BP control and nocturnal BP dipping status, both related to adverse outcomes. However, few studies have assessed the prognostic role of combining information on dipping status and achieved ambulatory BP in patients with chronic kidney disease (CKD). STUDY DESIGN: Prospective observational cohort study. SETTING & PARTICIPANTS: 906 patients with hypertension and CKD attending 1 of 3 Italian nephrology clinics. EXPOSURE: Four groups were defined by simultaneously classifying systolic ambulatory BP levels as being at goal (daytime SBP <135 and nighttime SBP <120 mm Hg) or above goal, and the presence or absence of nocturnal dipping (nighttime to daytime SBP ratio of <0.9 versus ≥0.9). OUTCOME: The composite of time to initiation of maintenance dialysis or estimated glomerular filtration rate (eGFR) decline ≥50%, and the composite of fatal and nonfatal cardiovascular events. ANALYTICAL APPROACH: Multivariable Cox proportional hazards models were used to estimate risks of kidney disease progression and cardiovascular disease in the 4 exposure groups where nocturnal dipping with systolic ambulatory BP at goal was the reference group. RESULTS: The mean patient age was 63.8 years, 61% were male, and 26.4% had diabetes; eGFR was 41.1 ± 20.8 mL/min/1.73 m2. The dipping prevalence in each of the 4 groups was as follows: nocturnal dipping with ambulatory BP at goal, 18.6%; no nocturnal dipping with ambulatory BP at goal, 20.5%; nocturnal dipping with ambulatory BP above goal, 11.8%; and no nocturnal dipping with ambulatory BP above goal, 49.1%. Among patients with ambulatory BP above goal, the risk of cardiovascular events was greater in the absence (HR, 2.79 [95% CI, 1.64-4.75]) and presence (HR, 2.05 [95% CI, 1.10-3.84]) of nocturnal dipping. The same held true for risk of kidney disease progression (HRs of 2.40 [95% CI, 1.58-3.65] and 2.11 [95% CI, 1.28-3.48] in the absence and presence of nocturnal dipping, respectively). Patients at the ambulatory BP goal but who did not experience nocturnal dipping had an increased risk of the cardiovascular end point (HR, 2.06 [95% CI, 1.15-3.68]) and the kidney disease progression outcome (HR, 1.82 [95% CI, 1.17-2.82]). LIMITATIONS: Lack of a diverse cohort (all those enrolled were White). Residual uncontrolled confounding. CONCLUSIONS: Systolic ambulatory BP above goal or the absence of nocturnal dipping, regardless of ambulatory BP, is associated with higher risks of cardiovascular disease and kidney disease progression among patients with CKD. PLAIN-LANGUAGE SUMMARY: Among patients with chronic kidney disease (CKD), ambulatory blood pressure (BP) monitoring improves the identification of individuals at high risk of clinical disease outcomes. Those with uncontrolled ambulatory BP are known to have a higher risk of developing cardiovascular disease and kidney disease progression, particularly when their ambulatory BP does not decline by at least 10% at night. Whether this is also true for patients with presence of optimal ambulatory BP levels but a BP pattern of no nighttime decline is largely unknown. We measured ambulatory BP in 900 Italian patients with CKD and followed them for several years. We found that, independent of ambulatory BP level, the absence of nighttime reductions in BP was associated with worsening of CKD and more frequent cardiovascular events. The absence of nighttime declines in BP is an independent risk factor for adverse events among patients with CKD. Future studies are needed to examine whether treating the absence of nighttime declines in BP improves clinical outcomes.
Subject(s)
Cardiovascular Diseases , Hypertension , Renal Insufficiency, Chronic , Humans , Male , Middle Aged , Female , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Blood Pressure/physiology , Blood Pressure Monitoring, Ambulatory , Prospective Studies , Hypertension/complications , Kidney , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/epidemiology , Renal Insufficiency, Chronic/therapy , Risk Factors , Disease Progression , Circadian Rhythm/physiologyABSTRACT
BACKGROUND: It is unknown whether faster progression of chronic kidney disease (CKD) in men than in women relates to differences in ambulatory blood pressure (ABP) levels. METHODS: We prospectively evaluated 906 hypertensive CKD patients (553 men) regularly followed in renal clinics to compare men versus women in terms of ABP control [daytime <135/85 and nighttime blood pressure (BP) <120/70 mmHg] and risk of all-cause mortality and end-stage kidney disease (ESKD). RESULTS: Age, estimated glomerular filtration rate and use of renin-angiotensin system inhibitors were similar in men and women, while proteinuria was lower in women [0.30 g/24 h interquartile range (IQR) 0.10-1.00 versus 0.42 g/24 h, IQR 0.10-1.28, P = 0.025]. No sex-difference was detected in office BP levels; conversely, daytime and nighttime BP were higher in men (134 ± 17/78 ± 11 and 127 ± 19/70 ± 11 mmHg) than in women (131 ± 16/75 ± 11, P = 0.005/P < 0.001 and 123 ± 20/67 ± 12, P = 0.006/P < 0.001), with ABP goal achieved more frequently in women (39.1% versus 25.1%, P < 0.001). During a median follow-up of 10.7 years, 275 patients reached ESKD (60.7% men) and 245 died (62.4% men). Risks of ESKD and mortality (hazard ratio and 95% confidence interval), adjusted for demographic and clinical variables, were higher in men (1.34, 1.02-1.76 and 1.36, 1.02-1.83, respectively). Adjustment for office BP at goal did not modify this association. In contrast, adjustment for ABP at goal attenuated the increased risk in men for ESKD (1.29, 0.98-1.70) and death (1.31, 0.98-1.77). In the fully adjusted model, ABP at goal was associated with reduced risk of ESKD (0.49, 0.34-0.70) and death (0.59, 0.43-0.80). No interaction between sex and ABP at goal on the risk of ESKD and death was found, suggesting that ABP-driven risks are consistent in males and females. CONCLUSIONS: Our study highlights that higher ABP significantly contributes to higher risks of ESKD and mortality in men.
Subject(s)
Hypertension , Kidney Failure, Chronic , Nephrology , Renal Insufficiency, Chronic , Blood Pressure , Blood Pressure Monitoring, Ambulatory , Female , Humans , Hypertension/epidemiology , Male , Prospective Studies , Renal Insufficiency, Chronic/epidemiology , Sex CharacteristicsABSTRACT
OBJECTIVES: Obesity is an important risk factor for morbidity and mortality. Vitamin K2 is involved in the production of bone and matrix amino acid g-carboxy-glutamic acid (Gla) proteins (vitamin K-dependent proteins [VKDPs]), regulating bone and vascular calcification (VC). Bone Gla protein (BGP) is involved both in bone mineralization and VCs. We assessed the relationships between vitamin K levels and body mass index (BMI) according to the hypothesis that the impact of BMI on mortality is partly driven by low vitamin K levels. METHODS: The Vitamin K Italian (VIKI) study included 387 hemodialysis patients from 18 dialysis centers in Italy. We determined plasma levels of bone markers: vitamin K levels, VKDPs, vitamin 25(OH)D, alkaline phosphatase (ALP), parathyroid hormone (PTH), calcium (Ca), phosphorus (P) and routine biochemistry. BMI was classified into the following categories: underweight (BMI < 18.5 kg/m2), normal weight (18.5 ≤ BMI < 25 kg/m2), overweight (25 ≤ BMI < 30 kg/m2) and obese (BMI ≥ 30 kg/m2). RESULTS: 45.2% of patients were overweight or obese. Stratification by BMI demonstrated lower median menaquinone-7 (MK7)/triglycerides levels in obese patients (0.42 ng/mg [0.19, 0.87], p = 0.005). BGP levels were lower in overweight and obese patients (152 mcg/L [83.2, 251] and 104 mcg/L [62.7, 230], p = <0.001). Furthermore, there was an inverse correlation between MK7/triglycerides levels and BMI (regression coefficient ß = -0.159; p = 0.003). In multiple linear regression, there was an inverse relationship between BGP levels and BMI (ß = - 0.119; p = 0.012). CONCLUSIONS: These data are the first to report an inverse relationship between Vitamin K2 levels and BMI in hemodialysis patients. Further studies are needed to confirm these findings and to determine if lower levels of Vitamin K are related to greater morbidity and mortality in this at-risk population.
Subject(s)
Overweight , Renal Dialysis , Humans , Obesity/complications , Triglycerides , Vitamin D , Vitamin K , Vitamin K 2ABSTRACT
The role of systemic inflammation is proving crucial in determining unfavorable outcome in SARS-CoV-2-infected patients. Limited data are available regarding immunosuppression management in kidney transplant recipients (KTRs) with SARS-CoV-2 pneumonia. We report a case of a 32-year-old KTR who developed SARS-CoV-2 infection and fully recovered in 15 days while maintaining standard immunosuppressive therapy.
Subject(s)
Coronavirus Infections/complications , Coronavirus Infections/therapy , Immunosuppressive Agents/administration & dosage , Kidney Failure, Chronic/complications , Kidney Transplantation , Pneumonia, Viral/complications , Pneumonia, Viral/therapy , Adult , Betacoronavirus , COVID-19 , Humans , Immunosuppression Therapy , Inflammation , Kidney Failure, Chronic/surgery , Male , Pandemics , SARS-CoV-2 , Transplant Recipients , Treatment OutcomeABSTRACT
Macrophage infiltration is associated with unfavorable kidney graft outcome in protocol biopsies, but few studies have evaluated its impact on clinical practice. We therefore prospectively evaluated 37 kidney transplant recipients (KTRs) who underwent kidney biopsy due to slight increases in serum creatinine, or mild proteinuria (>0.3 g/24 hr), in the first post-transplant year. Banff score, CD68+ count (score 0-3) by immunohistochemistry, and 1-year DSA were assessed. DGF was reported in 10 (27%) patients, 6 (16%) had normal biopsy, 7 (19%) borderline lesions, 13 (35%) IFTA, and 11 (30%) other lesions. Fifteen KTRs had grade 3 CD68+ infiltration, and 47% developed de novo DSA. During a 6.2 ± 2.7 year follow-up, four patients (11%) suffered from biopsy-proven T-cell rejection, 17 KTRs (46%) lost their graft (12 in the grade 3 CD68+ group). Graft survival was lower in KTRs with grade 3 CD68+ infiltration (P = 0.0074; log-rank test). Grade 3 CD68+ infiltrate was an independent predictor of graft loss (HR 5.41, 95% CI 1.74-16.8; P = 0.003), together with more severe graft dysfunction at biopsy (HR 6.41, 95% CI 2.57-16; P < 0.001). We conclude that grade 3 CD68+ interstitial infiltration is associated with increased risk of subsequent graft loss independent of other factors.
Subject(s)
Graft Rejection/etiology , Graft Survival/immunology , Kidney Transplantation/adverse effects , Kidney Tubules/pathology , Macrophages/pathology , Primary Graft Dysfunction/epidemiology , Adolescent , Adult , Aged , Female , Follow-Up Studies , Graft Rejection/pathology , Humans , Incidence , Italy/epidemiology , Kidney Tubules/immunology , Longitudinal Studies , Macrophages/immunology , Male , Middle Aged , Primary Graft Dysfunction/pathology , Prognosis , Prospective Studies , Risk Factors , Young AdultABSTRACT
Hepatitis C virus (HCV) infection is now considered a systemic disease due to the occurrence of extra-hepatic manifestations. Among these, the renal involvement is frequent. HCV infection, in fact, is strongly associated with proteinuria and chronic kidney disease (CKD) and negatively affects the prognosis of renal patients. In the last few years, availability of more specific and effective drugs against HCV has dramatically changed the clinical course of this disease. These drugs may provide further advantages in the CKD population as a whole by reducing progression of renal disease, mortality rate and by increasing the survival of graft in renal transplant recipients. The strict pathogenetic and prognostic link between HCV infection and CKD requires an ongoing relationship among the healthcare professionals involved in the treatment of both HCV infection and CKD. Therefore, Scientific Societies involved in the care of this high-risk population in Italy have organized a joint expert panel. The aim of the panel is to produce a position statement that can be used in daily clinical practice for the management of HCV infected patients across the whole spectrum of renal disease, from the conservative phase to renal replacement treatments (dialysis and transplantation). Sharing specific evidence-based expertise of different professional healthcare is the first step to obtain a common ground of knowledge on which to instate a model for multidisciplinary management of this high-risk population. Statements cover seven areas including epidemiology of CKD, HCV-induced glomerular damage, HCV-related renal risk, staging of liver disease in patients with CKD, prevention of transmission of HCV in hemodialysis units, treatment of HCV infection and management of HCV in kidney transplantation.
Subject(s)
Hepatitis C/therapy , Renal Insufficiency, Chronic/therapy , Hepacivirus/physiology , Hepatitis C/virology , Humans , Italy , Renal Insufficiency, Chronic/virologyABSTRACT
BACKGROUND: Asymptomatic left ventricular hypertrophy (LVH) is highly prevalent and associated with an adverse outcome in renal transplant recipients (RTRs). Nonetheless, there are currently no available studies analyzing the effect of LVH regression on solid clinical endpoints in these patients. METHODS: This study is the prospective observational extension of two randomized controlled trials aimed at assessing the effect of active intervention on post-transplant LVH in RTRs. We evaluated the incidence of a composite of death and any cardiovascular (CV) or renal event in 60 RTRs in whom LVH regression was observed and in 40 whose LVH remained unchanged or worsened. RESULTS: During an 8.4 ± 3.5-year follow-up, 8 deaths, 18 CV events and 6 renal events occurred in the entire cohort. Multivariable analysis showed that age [hazard ratio (HR) 1.07, 95% confidence interval (CI) 1.03-1.12 each 1 year, P = 0.002] and LVH regression (HR 0.42, 95% CI 0.22-0.87, P = 0.019) were significant predictors of the composite endpoint. Kaplan-Meier estimates showed better survival rates in patients in whom actual LVH regression was achieved (P < 0.001, log-rank test). Age (HR 1.09, 95% CI 1.03-1.15 each 1 year, P = 0.004), better graft function (HR 0.95, 95% CI 0.91-0.99 each 1 mL/min/1.73 m(2) increase in estimated glomerular filtration rate, P = 0.03) and LVH regression (HR 0.41, 95% CI 0.22-0.79, P = 0.01) were significant predictors of the CV endpoint. Patients with a left ventricular mass index decrease also showed better cardiac event-free survival (P = 0.0022, log-rank test). CONCLUSIONS: This is the first study to demonstrate that LVH regression, regardless of the therapeutic strategy adopted to achieve it, portends better long-term clinical outcome in RTRs.
Subject(s)
Hypertrophy, Left Ventricular/pathology , Renal Insufficiency, Chronic/pathology , Adult , Aged , Disease Progression , Disease-Free Survival , Female , Heart Ventricles/pathology , Humans , Hypertrophy, Left Ventricular/mortality , Incidence , Kaplan-Meier Estimate , Kidney Transplantation , Male , Middle Aged , Proportional Hazards Models , Prospective Studies , Renal Insufficiency, Chronic/mortality , Renal Insufficiency, Chronic/surgery , Survival Rate , Transplant Recipients , Treatment OutcomeABSTRACT
An emergent hypothesis is that a resistance to the anabolic drive by insulin may contribute to loss of strength and muscle mass in patients with chronic kidney disease (CKD). We tested whether insulin resistance extends to protein metabolism using the forearm perfusion method with arterial insulin infusion in 7 patients with CKD and metabolic acidosis (bicarbonate 19 mmol/l) and 7 control individuals. Forearm glucose balance and protein turnover (2H-phenylalanine kinetics) were measured basally and in response to insulin infused at different rates for 2 h to increase local forearm plasma insulin concentration by approximately 20 and 50 µU/ml. In response to insulin, forearm glucose uptake was significantly increased to a lesser extent (-40%) in patients with CKD than controls. In addition, whereas in the controls net muscle protein balance and protein degradation were decreased by both insulin infusion rates, in patients with CKD net protein balance and protein degradation were sensitive to the high (0.035 mU/kg per min) but not the low (0.01 mU/kg per min) insulin infusion. Besides blunting muscle glucose uptake, CKD and acidosis interfere with the normal suppression of protein degradation in response to a moderate rise in plasma insulin. Thus, alteration of protein metabolism by insulin may lead to changes in body tissue composition which may become clinically evident in conditions characterized by low insulinemia.
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Altered left ventricular (LV) mass and function are classical hallmarks of cardiomyopathy in chronic kidney disease (CKD). The left atrium (LA), a heart chamber exquisitely sensitive to volume overload and diastolic function, is an independent predictor of death and adverse cardiovascular (CV) events in high-risk patients such as those with hypertension and/or with heart failure. In this review we focus on the relationship of LA size with LV diastolic function, and the association between LA enlargement and CV and renal outcomes in patients with CKD, including patients with end-stage renal disease. Increased LA size emerges as a powerful predictor of mortality and major adverse CV events in both end-stage and early CKD, and some studies also show a close association between enlarged LA and renal disease progression. Secondary analyses of clinical trials suggest that the LA has the potential to be elected as a surrogate end point in CKD patients but the issue remains to be tested in specifically designed clinical studies.
Subject(s)
Cardiovascular Diseases/etiology , Heart Atria/pathology , Renal Insufficiency, Chronic/complications , Ventricular Dysfunction, Left/physiopathology , Disease Progression , Humans , Risk FactorsABSTRACT
INTRODUCTION: In recent years, thanks to significant advances in basic science and biotechnologies, nephrology has witnessed a deeper understanding of the mechanisms leading to various conditions associated with or causing kidney disease, opening new perspectives for developing specific treatments. These new possibilities have brought increased challenges to physicians, who face with a new complexity in disease characterization and selection the right treatment for individual patients. AREAS COVERED: We chose four therapeutic situations: anaemia in chronic kidney disease (CKD), heart failure in CKD, IgA nephropathy (IgAN) and membranous nephropathy (MN). The literature search was made through PubMed. EXPERT OPINION: Anaemia management remains challenging in CKD; a personalized therapeutic approach is often needed. Identifying patients who could benefit from a specific therapy is also an important goal for patients with CKD and heart failure with reduced ejection fraction. Several new treatments are under clinical development for IgAN; interestingly, they target specifically the pathogenetic mechanisms of the disease. The understanding of MN pathogenesis as an autoimmune disease and the discovery of several autoantibodies allows a better characterization of patients. High-sensible techniques for lymphocyte counting open the possibility of more personalized use of anti CD20 therapies.
Subject(s)
Anemia , Glomerulonephritis, IGA , Glomerulonephritis, Membranous , Heart Failure , Precision Medicine , Renal Insufficiency, Chronic , Humans , Renal Insufficiency, Chronic/drug therapy , Precision Medicine/methods , Glomerulonephritis, IGA/drug therapy , Heart Failure/drug therapy , Anemia/drug therapy , Anemia/etiology , Glomerulonephritis, Membranous/drug therapy , Glomerulonephritis, Membranous/immunologyABSTRACT
Resistance to erythropoiesis-stimulating agents (ESAs) has been observed in a considerable proportion of patients with chronic kidney disease (CKD) and it is reportedly associated with adverse outcomes, such as increased cardiovascular morbidity, faster progression to end-stage renal disease (ESRD) and all-cause mortality. The major causes of ESA resistance include chronic inflammation producing suppressive cytokines of early erythroid progenitor proliferation. In addition, pro-inflammatory cytokines stimulate hepcidin synthesis thus reducing iron availability for late erythropoiesis. Recent studies showing an association in deficiencies of the vitamin D axis with low haemoglobin (Hb) levels and ESA resistance suggest a new pathophysiological co-factor of renal anaemia. The administration of either native or active vitamin D has been associated with an improvement of anaemia and reduction in ESA requirements. Notably, these effects are not related to parathyroid hormone (PTH) values and seem to be independent on PTH suppression. Another possible explanation may be that calcitriol directly stimulates erythroid progenitors; however, this proliferative effect by extra-renal activation of 1α-hydroxylase enzyme is only a hypothesis. The majority of studies concerning vitamin D deficiency or supplementation, and degree of renal anaemia, point out the prevalent role of inflammation in the mechanism underlying these associations. Immune cells express the vitamin D receptor (VDR) which in turn is involved in the modulation of innate and adaptive immunity. VDR activation inhibits the expression of inflammatory cytokines in stromal and accessory cells and up-regulates the lymphocytic release of interleukin-10 (IL-10) exerting both anti-inflammatory activity and proliferative effects on erythroid progenitors. In CKD patients, vitamin D deficiency may stimulate immune cells within the bone marrow micro-environment to produce cytokines, inducing impaired erythropoiesis. Immune activation involves the reticuloendothelial system, increasing hepcidin synthesis and functional iron deficiency. Consequences of this inflammatory cascade are erythropoietin (EPO) resistance and anaemia. Given the key role of inflammation in the response to EPO, the therapeutic use of agents with anti-cytokines properties, such as vitamin D and paricalcitol, may provide benefit in the prevention/treatment of ESA hyporesponsiveness.
Subject(s)
Anemia/drug therapy , Erythropoietin/pharmacology , Renal Insufficiency, Chronic/complications , Vitamin D Deficiency/complications , Anemia/etiology , Animals , Cytokines/metabolism , Humans , Inflammation/drug therapy , Inflammation/etiologyABSTRACT
INTRODUCTION: Erythropoiesis-stimulating agents (ESAs) are the standard of treatment for anemia in chronic kidney disease. Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHI) are small molecules that stimulate endogenous erythropoietin synthesis. AREAS COVERED: The cardiovascular safety of ESAs and HIF-PHIs. We performed a PubMed search using several key words, including anemia, chronic kidney disease, safety, erythropoiesis stimulating agents, HIF-PH inhibitors. EXPERT OPINION: ESAs are well-tolerated drugs with a long history of use; there are safety concerns, especially when targeting high hemoglobin levels. HIF-PHIs have comparable efficacy to ESAs in correcting anemia. Contrary to expectations, randomized phase 3 clinical trials have shown that overall HIF-PHIs were non-inferior to ESA or placebo with respect to the risk of cardiovascular endpoints. In addition, some phase 3 trials raised potential safety concerns regarding cardiovascular and thrombotic events, particularly in non-dialysis patients.Today, HIF-PHIs represent an additional treatment option for anemia in patients with chronic kidney disease. This has made the management of anemia in CKD more complex and heterogeneous. A better understanding of the mechanisms causing hypo-responsiveness to ESAs, combined with an individualized approach that balances ESAs, HIF-PHIs and iron doses, could increase the benefits while reducing the risks.
Subject(s)
Anemia , Erythropoietin , Hematinics , Renal Insufficiency, Chronic , Humans , Anemia/etiology , Anemia/chemically induced , Erythropoietin/therapeutic use , Iron/therapeutic use , Hematinics/adverse effects , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/drug therapyABSTRACT
Chronic kidney disease (CKD) is a common feature of sickle cell disease (SCD). The awareness of the clinical presentation and renal involvement in patients affected by hemoglobinopathies is greatly needed. Patient management is particularly complex, especially with kidney transplantation. We, therefore, report the case of a 56-year-old patient affected by sickle cell trait who underwent kidney transplantation. This case will underline all the various challenges the nephrologist must face in this clinical setting and their management.
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Hyperkalaemia is a life-threatening condition leading to significant morbidity and mortality. It is common in heart failure and in chronic kidney disease (CKD) patients due to the diseases themselves, which often coexist, the high co-presence of diabetes, the fluctuations in renal function, and the use of some drugs [i.e. renin-angiotensin-aldosterone system (RAAS) inhibitors]. Hyperkalaemia limits their administration or uptitration, thus impacting on mortality. New K + binders, namely patiromer and sodium zirconium cyclosilicate (ZS-9), are an intriguing option to manage hyperkalaemia in heart failure and/or CKD patients, both to reduce its fatal effects and to let clinicians uptitrate RAAS inhibition. Even if their real impact on strong outcomes is still to be determined, we hereby provide a practical approach to favour their use in routine clinical practice in order to gain the correct confidence and provide an additive tool to heart failure and CKD patients' wellbeing. New trials are welcome to fill the gap in knowledge.
Subject(s)
Heart Failure , Hyperkalemia , Renal Insufficiency, Chronic , Humans , Hyperkalemia/chemically induced , Hyperkalemia/drug therapy , Hyperkalemia/complications , Potassium/pharmacology , Renin-Angiotensin System , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/drug therapy , Heart Failure/drug therapy , Heart Failure/complicationsABSTRACT
The frequent coexistence in daily clinical practice of chronic kidney disease (CKD) and atrial fibrillation (AF), especially in the elderly, represents a conundrum for physicians, mainly related to the management of anticoagulant therapy. The reduction of estimated glomerular filtration rate (eGFR) impairs anticoagulant clearance, increasing bleeding propensity. Moreover, dysfunctional responses of endothelial cells and inflammatory systems both trigger thromboembolic status. Those mechanisms pose an increased risk of adverse events for AF patients with CKD. While several data suggested the use of direct oral anticoagulants (DOACs) over warfarin as preferred anticoagulant strategy in patients with Stage 3A to Stage 4 CKD (eGFR range of 15-49 mL/min/1.73 m2), less is known about the optimal anticoagulation management in patients with end-stage renal disease (ESRD) or on renal replacement therapy (RRT). Furthermore, a pivotal feature to be considered when choosing the anticoagulant drug in CKD patients is represented by nephroprotective capability. Indeed, anticoagulant therapy with warfarin showed detrimental effects on kidney function, whereas DOACs demonstrated a beneficial effect on renal function preservation. Mounting data showed that, when pharmacological treatment cannot be pursued due to contraindication to anticoagulation, left atrial appendage occlusion (LAAO) may represent a valid alternative. This brief review outlines the current knowledge regarding anticoagulation therapy in ESRD/RRT patients, reporting new lines of evidence on the nephroprotective effect of oral anticoagulants and on the use of LAAO as a non-pharmacological alternative to oral anticoagulation.
Subject(s)
Atrial Fibrillation , Kidney Failure, Chronic , Renal Insufficiency, Chronic , Stroke , Humans , Aged , Anticoagulants/adverse effects , Atrial Fibrillation/complications , Atrial Fibrillation/drug therapy , Warfarin/adverse effects , Endothelial Cells , Stroke/prevention & control , Stroke/complications , Administration, Oral , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/therapy , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/drug therapyABSTRACT
BACKGROUND: Left ventricular (LV) diastolic dysfunction is common in non-dialysis chronic kidney disease (ND-CKD) patients; however, the prevalence estimated according to the new diagnostic criteria as well as the prognostic role of diastolic dysfunction on CKD progression remain unknown. METHOD: We longitudinally evaluated consecutive ND-CKD patients and preserved systolic function (LV ejection fraction > 50%). According to the recently updated guidelines, LV diastolic dysfunction was assessed by four echocardiographic variables (annular e' velocity, average mitral valve E-wave/e' ratio, left atrial volume index and tricuspid regurgitation). Patients were classified as diastolic dysfunction, indeterminate and normal. Time-dependent estimated glomerular filtration rate (eGFR) change was assessed by mixed-effects regression model. Cumulative incidence of composite renal outcome (eGFR decline > 50% or chronic dialysis) was also estimated. RESULTS: Among 140 patients (age 66.2â±â14.5 years; 61% males; eGFR 39.8â±â21.8âml/min per 1.73m2; 43.6% diabetics), diastolic dysfunction occurred in 22.9%, indeterminate in 45.7% and normal in 31.4%. Prevalence of diastolic dysfunction was much lower than that estimated with older criteria (62.7%). Logistic regression (odds ratio, 95% confidence interval [CI]) showed that diastolic dysfunction was associated with lower eGFR (0.97, 0.94-0.99), older age (1.04, 1.01-1.06) and night-time systolic blood pressure (1.04, 1.00-1.07). Across 1702 eGFR measurements collected during a median follow-up of 4.6âyears, eGFR decline (ml/min per 1.73m2; per year) was faster in patients with diastolic dysfunction (-2.12, 95% CI from -2.68 to -1.56) and in the indeterminate (11.2/100âpts per year) as compared to normal (-1.14, 95% CI from -1.64 to -0.63). Incidence of composite renal outcome was significantly higher in diastolic dysfunction (13.8/100âpts/year) than in normal group (3.5/100âpts per year)'. CONCLUSION: In ND-CKD population, LV diastolic dysfunction is less frequent than previously described and acts as independent predictor of CKD progression.
Subject(s)
Renal Insufficiency, Chronic , Ventricular Dysfunction, Left , Aged , Aged, 80 and over , Diastole/physiology , Female , Humans , Male , Middle Aged , Prevalence , Prognosis , Renal Dialysis/adverse effects , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/epidemiology , Ventricular Dysfunction, Left/etiology , Ventricular Function, Left/physiologyABSTRACT
Atrial fibrillation (AF) and chronic kidney disease (CKD) are strictly related and share several risk factors (i.e. hypertension, diabetes mellitus, congestive heart failure). As consequence, AF is very common among CKD patients, especially in those with end stage renal disease (ESRD). Moreover, patients with AF and advanced kidney disease have a higher mortality rate than patients with preserved renal function due to an increased incidence of stroke and an unpredicted elevated hemorrhagic risk. The adequate long-term oral anticoagulation in this subgroup of patients represents a major challenging issue faced by physicians in clinical practice. Direct oral anticoagulants (DOACs) are currently contraindicated in patients with ESRD while vitamin K antagonists (VKAs) are characterized by a narrow therapeutic window, increased tissue calcification and an unfavorable risk/benefit ratio with low stroke prevention effect and augmented risk of major bleeding. The purpose of this review is to shed light on the applications of DOAC therapy in CKD patients, especially in ESRD patients.
Subject(s)
Atrial Fibrillation , Courage , Kidney Failure, Chronic , Renal Insufficiency, Chronic , Stroke , Administration, Oral , Anticoagulants/adverse effects , Atrial Fibrillation/complications , Atrial Fibrillation/drug therapy , Female , Humans , Kidney Failure, Chronic/chemically induced , Male , Renal Insufficiency, Chronic/drug therapy , Stroke/etiology , Stroke/prevention & controlABSTRACT
Background/aim: Direct-acting antivirals (DAAs) have improved the treatment of HCV-positive kidney transplant recipients (KTRs). However, their medium-term follow-up effects on graft function are conflicting. This study aimed to analyze how the interplay between DAAs, calcineurin inhibitors (CNI), and HCV eradication impacts 12-month kidney graft function. Methods: This double-center retrospective study with a prospective follow-up enrolled 35 KTRs with HCV treated with DAAs for 12 weeks. We compared three parameters: estimated glomerular filtration rate (eGFR), 24-h proteinuria, and CNI trough levels at three time points: baseline, end of treatment (EOT), and 12 months later. Results: Kidney allograft function remained stable when comparing baseline and 12-month post-treatment values of eGFR (60.7 versus 57.8 ml/min; p = 0.28) and 24-h proteinuria (0.3 versus 0.2 g/24 h; p = 0.15), while tacrolimus (Tac) trough levels underwent a statistically significant decline (6.9 versus 5.4 ng/ml; p = 0.004). Using an ongoing triple Tac-based maintenance therapy as a conservative measure, a dose escalation of Tac was applied only in seven patients. No variation in CyA and mTOR levels was detected. Conclusion: DAA therapy is safe and effective in HCV-positive KTRs. It also produces a persistent significant reduction in Tac trough levels that does not influence graft function at 12 months.