scholarly journals Lithium and Renal Impairment: A Review on a Still Hot Topic

2018 ◽  
Vol 51 (05) ◽  
pp. 200-205 ◽  
Author(s):  
René Nielsen ◽  
Lars Kessing ◽  
Willem Nolen ◽  
Rasmus Licht

Abstract Introduction Lithium is established as an effective treatment of mania, of depression in bipolar and unipolar disorder, and in maintenance treatment of these disorders. However, due to the necessity of monitoring and concerns about irreversible adverse effects, in particular renal impairment, after long-term use, lithium might be underutilized. Methods This study reviewed 6 large observational studies addressing the risk of impaired renal function associated with lithium treatment and methodological issues impacting interpretation of results. Results An increased risk of renal impairment associated with lithium treatment is suggested. This increased risk may, at least partly, be a result of surveillance bias. Additionally, the earliest studies pointed toward an increased risk of end-stage renal disease associated with lithium treatment, whereas the later and methodologically most sound studies do not. Discussion The improved renal outcome found in the more recent lithium studies may be a result of improved monitoring and focus on recommended serum levels (preferentially 0.6–0.8 mmol/L) as compared to poorer renal outcome in studies with patients treated in the 1960s to 1980s.

Author(s):  
Lorraine Harper ◽  
David Jayne

The goals of treatment in renal vasculitis are to stop vasculitic activity and recover renal function. Subsequent strategies are required to prevent vasculitis returning and to address longer-term co-morbidities caused by tissue damage, drug toxicity, and increased cardiovascular and malignancy risk.Cyclophosphamide and high-dose glucocorticoids remain the standard induction therapy with alternative immunosuppressives, such as azathioprine, to prevent relapse. Plasma exchange improves renal recovery in severe presentations. Refractory disease resulting from a failure of induction or remission maintenance therapy requires alternative agents and rituximab has been particularly effective. Replacement of cyclophosphamide by rituximab for remission induction is supported by recent evidence. Methotrexate is effective in non-renal vasculitis but difficult to use in patients with renal impairment. Mycophenolate mofetil seems to be effective but there is less long-term evidence.Drug toxicity contributes to co-morbidity and mortality and has led to newer regimens with reduced cyclophosphamide exposure. Glucocorticoid toxicity remains a major problem with controversy over the rapidity with which glucocorticoids can be reduced or withdrawn.Disease relapse occurs in about 50% of patients. Early detection is less likely to lead to an adverse affect on outcomes. Rates of cardiovascular disease and malignancy are higher than in control populations but strategies to reduce their risk, apart from cyclophosphamide-sparing regimens, have not been developed. Thromboembolic events occur in 10% and may be linked to the recently identified autoantibodies to plasminogen and tissue plasminogen activator.Renal impairment at diagnosis is a strong predictor of patient survival and renal outcome. Other predictors include patient age, antineutrophil cytoplasmic antibody subtype, disease extent and response to therapy. Chronic kidney disease can stabilize for many years but the risks of end-stage renal disease are increased by acute kidney injury at presentation or renal relapse. Renal transplantation is successful with similar outcomes to other causes of end-stage renal disease.


2020 ◽  
Vol 105 (4) ◽  
pp. e1772-e1780 ◽  
Author(s):  
João Sérgio Neves ◽  
Simon Correa ◽  
Rute Baeta Baptista ◽  
Miguel Bigotte Vieira ◽  
Sushrut S Waikar ◽  
...  

Abstract Purpose Despite our understanding of diabetes as an established risk factor for progressive kidney disease and cardiac complications, the prognostic significance of prediabetes in patients with chronic kidney disease (CKD) remains largely unknown. Methods Participants of the Chronic Renal Insufficiency Cohort (CRIC) were categorized as having normoglycemia, prediabetes, or diabetes according to fasting plasma glucose, glycated hemoglobin A1c (HbA1c), and treatment with antidiabetic drugs at baseline. Unadjusted and adjusted proportional hazards models were fit to estimate the association of prediabetes and diabetes (versus normoglycemia) with: (1) composite renal outcome (end-stage renal disease, 50% decline in estimated glomerular filtration rate to ≤ 15 mL/min/1.73 m2, or doubling of urine protein-to-creatinine ratio to ≥ 0.22 g/g creatinine); (2) composite cardiovascular (CV) outcome (congestive heart failure, myocardial infarction or stroke); and (3) all-cause mortality. Results Of the 3701 individuals analyzed, 945 were normoglycemic, 847 had prediabetes and 1909 had diabetes. The median follow-up was 7.5 years. Prediabetes was not associated with the composite renal outcome (adjusted hazard ratio [aHR] 1.13; 95% confidence interval [CI], 0.96–1.32; P = 0.14), but was associated with proteinuria progression (aHR 1.23; 95% CI, 1.03–1.47; P = 0.02). Prediabetes was associated with a higher risk of the composite CV outcome (aHR 1.38; 95% CI, 1.05–1.82; P = 0.02) and a trend towards all-cause mortality (aHR 1.28; 95% CI, 0.99–1.66; P = 0.07). Participants with diabetes had an increased risk of the composite renal outcome, the composite CV outcome, and all-cause mortality. Conclusions In individuals with CKD, prediabetes was not associated with composite renal outcome, but was associated with an increased risk of proteinuria progression and adverse CV outcomes.


2020 ◽  
Vol 19 (1) ◽  
pp. 41-54 ◽  
Author(s):  
Stefanos Roumeliotis ◽  
Athanasios Roumeliotis ◽  
Xenia Gorny ◽  
Peter R. Mertens

In end-stage renal disease patients, the leading causes of mortality are of cardiovascular (CV) origin. The underlying mechanisms are complex, given that sudden heart failure is more common than acute myocardial infarction. A contributing role of oxidative stress is postulated, which is increased even at early stages of chronic kidney disease, is gradually augmented in parallel to progression to endstage renal disease and is further accelerated by renal replacement therapy. Oxidative stress ensues when there is an imbalance between reactive pro-oxidants and physiologically occurring electron donating antioxidant defence systems. During the last decade, a close association of oxidative stress with accelerated atherosclerosis and increased risk for CV and all-cause mortality has been established. Lipid peroxidation has been identified as a trigger for endothelial dysfunction, the first step towards atherogenesis. In order to counteract the deleterious effects of free radicals and thereby ameliorate, or delay, CV disease, exogenous administration of antioxidants has been proposed. Here, we attempt to summarize existing data from studies that test antioxidants for CV protection, such as vitamins E and C, statins, omega-3 fatty acids and N-acetylcysteine.


2021 ◽  
Vol 22 (12) ◽  
pp. 6196
Author(s):  
Anna Pieniazek ◽  
Joanna Bernasinska-Slomczewska ◽  
Lukasz Gwozdzinski

The presence of toxins is believed to be a major factor in the development of uremia in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD). Uremic toxins have been divided into 3 groups: small substances dissolved in water, medium molecules: peptides and low molecular weight proteins, and protein-bound toxins. One of the earliest known toxins is urea, the concentration of which was considered negligible in CKD patients. However, subsequent studies have shown that it can lead to increased production of reactive oxygen species (ROS), and induce insulin resistance in vitro and in vivo, as well as cause carbamylation of proteins, peptides, and amino acids. Other uremic toxins and their participation in the damage caused by oxidative stress to biological material are also presented. Macromolecules and molecules modified as a result of carbamylation, oxidative stress, and their adducts with uremic toxins, may lead to cardiovascular diseases, and increased risk of mortality in patients with CKD.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Stanislas Werfel ◽  
Georg Lorenz ◽  
Bernhard Haller ◽  
Roman Günthner ◽  
Julia Matschkal ◽  
...  

AbstractCohort studies often provide a large array of data on study participants. The techniques of statistical learning can allow an efficient way to analyze large datasets in order to uncover previously unknown, clinically relevant predictors of morbidity or mortality. We applied a combination of elastic net penalized Cox regression and stability selection with the aim of identifying novel predictors of mortality in a cohort of prevalent hemodialysis patients. In our analysis we included 475 patients from the “rISk strAtification in end-stage Renal disease” (ISAR) study, who we split into derivation and confirmation cohorts. A wide array of examinations was available for study participants, resulting in over a hundred potential predictors. In the selection approach many of the well established predictors were retrieved in the derivation cohort. Additionally, the serum levels of IL-12p70 and AST were selected as mortality predictors and confirmed in the withheld subgroup. High IL-12p70 levels were specifically prognostic of infection-related mortality. In summary, we demonstrate an approach how statistical learning can be applied to a cohort study to derive novel hypotheses in a data-driven way. Our results suggest a novel role of IL-12p70 in infection-related mortality, while AST is a promising additional biomarker in patients undergoing hemodialysis.


2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Cristina Mega ◽  
Edite Teixeira-de-Lemos ◽  
Rosa Fernandes ◽  
Flávio Reis

Diabetic nephropathy (DN) is now the single commonest cause of end-stage renal disease (ESRD) worldwide and one of the main causes of death in diabetic patients. It is also acknowledged as an independent risk factor for cardiovascular disease (CVD). Since sitagliptin was approved, many studies have been carried out revealing its ability to not only improve metabolic control but also ameliorate dysfunction in various diabetes-targeted organs, especially the kidney, due to putative underlying cytoprotective properties, namely, its antiapoptotic, antioxidant, anti-inflammatory, and antifibrotic properties. Despite overall recommendations, many patients spend a long time well outside the recommended glycaemic range and, therefore, have an increased risk for developing micro- and macrovascular complications. Currently, it is becoming clearer that type 2 diabetes mellitus (T2DM) management must envision not only the improvement in glycaemic control but also, and particularly, the prevention of pancreatic deterioration and the evolution of complications, such as DN. This review aims to provide an overview of the current knowledge in the field of renoprotective actions of sitagliptin, namely, improvement in diabetic dysmetabolism, hemodynamic factors, renal function, diabetic kidney lesions, and cytoprotective properties.


Author(s):  
Amit N Vora ◽  
Maggie A Stanislawski ◽  
John S Rumsfeld ◽  
Thomas M Maddox ◽  
Mladen Vidovich ◽  
...  

Background: Patients with chronic kidney disease (CKD) are at increased risk of bleeding and transfusion after cardiac catheterization. Whether rates of these complications or progression to new dialysis are increased in this high-risk population undergoing transradial (TR) access compared to transfemoral (TF) access is unknown. Methods: From the Veterans Affairs Clinical Assessment, Reporting, and Tracking (CART) Program between 10/2007-09/2012 we identified 40,160 CKD patients undergoing cardiac catheterization with baseline glomerular filtration rate (GFR) ≤ 60 ml/min. We used multivariable Cox modeling to determine the independent association between TR access and post-procedure transfusion as well as progression to new dialysis using TF as the reference. Results: Overall, 3,828 (9.5%) of CKD patients underwent TR access and tended to be slightly younger but overall had similar rates of CKD severity compared with TF patients (GFR 45-60 ml/min: 77.0% vs. 77.0%; GFR 30-44 ml/min: 19.7% vs. 19.3%; GFR 15-29 ml/min: 3.3% vs. 3.7%, p=0.35). TR patients had longer fluoroscopy times (8.1 vs 6.9 minutes, p=<0.0001) but decreased contrast use (90.0 vs 100.0 ml, p=<0.0001). Among the 31,692 patients with a full year of follow-up, 42 (1.7%) of TR patients and 545 (1.9%) of TF patients progressed to new dialysis within 1 year (p=0.64). However, only 33 (0.9%) of TR patients compared with 570 TF patients (1.6%) needed post-procedure blood transfusion (p=0.0006). After multivariable adjustment, there was no significant difference in progression to ESRD between TR and TF patients but TR was associated with a significant decrease in transfusion (Figure). Conclusion: Among CKD patients undergoing cardiac catheterization in the VA health system, TR access is associated with a decreased risk for post-procedure transfusion compared with TF access. There was no significant difference between the two approaches with respect to progression to ESRD. These data suggest that TR is a reasonable option for patients with any level of CKD undergoing cardiac catheterization.


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