The Rising Risk of Chronic Kidney Disease (CKD) and How it is Dealt With: A Review of Current and Potential Phosphate Binders (PB)

2021 ◽  
Vol 21 ◽  
Author(s):  
Robert Gosik ◽  
Krzysztof Danel
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Aluminum Toxicity ◽  
Positive Influence ◽  
Phosphate Binders ◽  
Lanthanum Hydroxide ◽  
Risk Of Death ◽  
Increased Risk ◽  
Gastrointestinal Side Effects ◽  
Crystal Accumulation

: It is estimated that by 2040 Chronic Kidney Disease (CKD) will be the 5th main cause of global deaths. It has been suggested that hyperphosphatemia is among the main factors leading to the increased risk of death. This review focuses on potential and currently used phosphate binders (PB). Aluminum hydroxide is presently not recommended due to potential aluminum toxicity. Calcium‑containing phosphate binders (CCPB) can cause calcium overload, resulting in hypercalcemia and an increased risk of cardiovascular diseases. Magnesium and calcium complexes were suggested to be as effective as sevelamer in the reduction of serum phosphate, with the potential to slow down the process of calcification. However, limited studies have been conducted in this area. Although sevelamer seemed to have a positive influence on cardiovascular calcification and arterial stiffness, its influence on mortality was unclear. Sevelamer crystal accumulation in the gastrointestinal tract (GI) can cause gastrointestinal bleeding. Lanthanum carbonate seemed to lower all-cause mortality and reduce the chance of hypercalcemia, even though a deposit in the GI tract was observed. Colestilan, like sevelamer, lowered LDL cholesterol. Sucroferric oxyhydroxide had a lower pill burden than other PBs, and it seemed to reduce serum FGF-23. Ferric citrate improved parameters that are related to anemia but can cause iron overload. Bixalomer appeared to have fewer gastrointestinal side effects than sevelamer. Nano-lanthanum hydroxide and SBR759 may have an interesting future as PBs. In conclusion, the development of new PBs should also take into consideration their potential to function as protection modifiers.

scholarly journals Outcomes of major trauma among patients with chronic kidney disease and receiving dialysis in Nova Scotia: a retrospective analysis

2021 ◽  
Vol 6 (1) ◽  
pp. e000672
Author(s):  
Ryan Pratt ◽  
Mete Erdogan ◽  
Robert Green ◽  
David Clark ◽  
Amanda Vinson ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Nova Scotia ◽  
Kidney Disease ◽  
Hospital Mortality ◽  
Major Trauma ◽  
Injury Severity ◽  
Cox Regression ◽  
Trauma Patients ◽  
Risk Of Death ◽  
Increased Risk

BackgroundThe risk of death and complications after major trauma in patients with chronic kidney disease (CKD) is higher than in the general population, but whether this association holds true among Canadian trauma patients is unknown.ObjectivesTo characterize patients with CKD/receiving dialysis within a regional major trauma cohort and compare their outcomes with patients without CKD.MethodsAll major traumas requiring hospitalization between 2006 and 2017 were identified from a provincial trauma registry in Nova Scotia, Canada. Trauma patients with stage ≥3 CKD (estimated glomerular filtration rate <60 mL/min/1.73 m2) or receiving dialysis were identified by cross-referencing two regional databases for nephrology clinics and dialysis treatments. The primary outcome was in-hospital mortality; secondary outcomes included hospital/intensive care unit (ICU) length of stay (LOS) and ventilator-days. Cox regression was used to adjust for the effects of patient characteristics on in-hospital mortality.ResultsIn total, 6237 trauma patients were identified, of whom 4997 lived within the regional nephrology catchment area. CKD/dialysis trauma patients (n=101; 28 on dialysis) were older than patients without CKD (n=4896), with higher rates of hypertension, diabetes, and cardiovascular disease, and had increased risk of in-hospital mortality (31% vs 11%, p<0.001). No differences were observed in injury severity, ICU LOS, or ventilator-days. After adjustment for age, sex, and injury severity, the HR for in-hospital mortality was 1.90 (95% CI 1.33 to 2.70) for CKD/dialysis compared with patients without CKD.ConclusionIndependent of injury severity, patients without CKD/dialysis have significantly increased risk of in-hospital mortality after major trauma.

MO817ALDOSTERONE ANTAGONISTS FOR PATIENTS WITH CHRONIC KIDNEY DISEASE REQUIRING DIALYSIS

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Takeshi Hasegawa ◽  
Hiroki Nihiwaki ◽  
Erika Ota ◽  
William Levack ◽  
Hisashi Noma
Keyword(s):  
Chronic Kidney Disease ◽  
High Risk ◽  
Kidney Disease ◽  
Standard Care ◽  
Meta Analysis ◽  
Cardiovascular Death ◽  
Aldosterone Antagonists ◽  
Mortality And Morbidity ◽  
Risk Of Death ◽  
Increased Risk

Abstract Background and Aims Patients with chronic kidney disease (CKD) undergoing dialysis are at a particularly high risk of cardiovascular mortality and morbidity. This systematic review and meta-analysis aimed to evaluate the benefits and harms of aldosterone antagonists, both non-selective (spironolactone) and selective (eplerenone), in comparison to control (placebo or standard care) in patients with CKD requiring haemodialysis or peritoneal dialysis. Method We searched the Cochrane Kidney and Transplant Register of Studies up to 29 July 2019 using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register Search Portal and ClinicalTrials.gov. We included individual and cluster randomised controlled trials (RCTs), cross-over trials, and quasi-RCTs that compared aldosterone antagonists with placebo or standard care in patients with CKD requiring dialysis. We used a random-effects model meta-analysis to perform a quantitative synthesis of the data. We used the I2 statistic to measure heterogeneity among the trials in each analysis. We indicated summary estimates as a risk ratio (RR) for dichotomous outcomes with their 95% confidence interval (CI). We assessed the certainty of the evidence for each of the main outcomes using the GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) approach. Results We included 16 trials (14 parallel RCTs and two cross-over trials) involving a total of 1,446 patients. Among included studies, 13 trials compared spironolactone to placebo or standard care and one trial compared eplerenone to a placebo. Most studies had an unclear or high risk of bias. Compared to control, aldosterone antagonists reduced the risk of all-cause death for patients with CKD requiring dialysis (9 trials, 1,119 patients: RR 0.45, 95% CI 0.30 to 0.67; moderate certainty of evidence). Aldosterone antagonist also decreased the risk of death due to cardiovascular disease (6 trials, 908 patients: RR 0.37, 95% CI 0.22 to 0.64; moderate certainty of evidence) and cardiovascular and cerebrovascular morbidity (3 trials, 328 patients: RR 0.38, 95% CI 0.18 to 0.76; moderate certainty of evidence). While aldosterone antagonists had an apparent increased risk of gynaecomastia compared with control (4 trials, 768 patients: RR 5.95, 95% CI 1.93 to 18.3; moderate certainty of evidence), the elevated risk of hyperkalaemia due to aldosterone antagonists was uncertain (9 trials, 981 patients: RR 1.41, 95% CI 0.72 to 2.78; low certainty of evidence). Conclusion Based on moderate certainty of the evidence, aldosterone antagonists could reduce the risk of all-cause and cardiovascular death and morbidity due to cardiovascular and cerebrovascular disease but increase the risk of gynaecomastia in patients with CKD requiring dialysis.

scholarly journals MO038SCARF EXPRESSION IN KIDNEY DISEASE

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Sol Carriazo ◽  
Maria Dolores Sanchez-Nino ◽  
Maria Vanessa Perez Gomez ◽  
Laura Castañeda-Infante ◽  
Catalina Martin ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Risk Factor ◽  
Kidney Disease ◽  
Single Cell ◽  
Kidney Tissue ◽  
Differentially Expressed ◽  
Tubular Cells ◽  
Risk Of Death ◽  
Increased Risk ◽  
The Impact

Abstract Background and Aims Chronic kidney disease (CKD) is the most common risk factor for lethal COVID19 and the risk factor that most increases the risk of death of COVID19 patients. Additionally, acute kidney injury (AKI) is frequent in COVID19 and AKI increases the risk of death. However, the underlying cellular and molecular mechanisms of such increased risk are unclear. SARS-CoV-2 and coronavirus-associated receptors and factors (SCARFs) are required for and/or regulate (in a positive or negative manner) coronary cell entry and/or viral replication. We have now studied changes in the expression of genes encoding for SCARF in the context of acute and chronic kidney disease. Method Data mining of in-house (experimental models of AKI -folic acid nephropathy- and CKD -Unilateral ureteral obstruction- in mice) and publicly available databases (Nephroseq, published single cell transcriptomics studies) of kidney tissue transcriptomics as well as the Protein Atlas database. Results Out of 28 SCARF genes identified by Singh et al (Cell Reports 2020), 26 were represented in the experimental AKI database. Of them 7 (27%) were differentially expressed during AKI (FDR &lt;0.05), 4 of them upregulated and 3 downregulated (Figure 1.A). Additionally, 27 were represented in the experimental CKD database. Of them 17 (63%) were differentially expressed during experimental CKD, 6 of them upregulated and 11 downregulated (Figure 1.B). Two genes were consistently upregulated (Ctsl and Ifitm3) and two consistently downregulated (Tmprss2 and Top3b) in both experimental AKI and CKD (Figure 1.A and B). They encode cathepsin L, interferon induced transmembrane protein 3, transmembrane serine protease 2, DNA topoisomerase III beta, respectively. Single cell transcriptomics databases localized Ctsl expression mainly to podocytes and tubular cells while protein atlas showed clear tubular staining. The main site of Ifitm3 was endothelium in both datasets and it was also localized to leukocytes by single cell transcriptomics. Tmprss2 was mainly localized to tubular cells in both datasets while Top3b was widely expressed in parenchymal renal cells, endothelium and leucocytes in single cell transcriptomics. Increased kidney expression of Ifitm3 and decreased expression of Tmprss2 and Top3b were confirmed in diverse CKD datasets in Nephroseq. Conclusion Both AKI and CKD are associated with differential expression of SCARF genes in kidney tissue, the impact of CKD appearing to be larger. Characterization of these changes and their functional impact in kidney tissue and beyond the kidneys may provide clues to the increased risk of severe or lethal COVID19 in kidney disease patients. Kidney SCARF gene expression

scholarly journals Increased risk of death and de novo chronic kidney disease following reversible acute kidney injury

2012 ◽  
Vol 81 (5) ◽  
pp. 477-485 ◽  
Author(s):  
Ion D. Bucaloiu ◽  
H Lester Kirchner ◽  
Evan R. Norfolk ◽  
James E. Hartle ◽  
Robert M. Perkins
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Kidney Disease ◽  
De Novo ◽  
Kidney Injury ◽  
Risk Of Death ◽  
Increased Risk

scholarly journals Renin–angiotensin system blocker discontinuation and adverse outcomes in chronic kidney disease

2020 ◽  
Author(s):  
Carl P Walther ◽  
Wolfgang C Winkelmayer ◽  
Peter A Richardson ◽  
Salim S Virani ◽  
Sankar D Navaneethan
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Renin Angiotensin System ◽  
Cox Proportional Hazards ◽  
Adverse Outcomes ◽  
Converting Enzyme Inhibitors ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Risk Of Death ◽  
Increased Risk

Abstract Background Treatment with renin–angiotensin system inhibitors (RASIs), angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) is the standard of care for those with chronic kidney disease (CKD) and albuminuria. However, ACEI/ARB treatment is often discontinued for various reasons. We investigated the association of ACEI/ARB discontinuation with outcomes among US veterans with non-dialysis-dependent CKD. Methods We performed a retrospective cohort study of patients in the Veterans Affairs healthcare system with non-dialysis-dependent CKD who subsequently were started on ACEI/ARB therapy (new user design). Discontinuation events were defined as a gap in ACEI/ARB therapy of ≥14 days and were classified further based on duration (14–30, 31–60, 61–90, 91–180 and &gt;180 days). This was treated as a time-varying risk factor in adjusted Cox proportional hazards models for the outcomes of death and incident end-stage kidney disease (ESKD), which also adjusted for relevant confounders. Results We identified 141 252 people with CKD and incident ACEI/ARB use who met the inclusion criteria; these were followed for a mean 4.87 years. There were 135 356 discontinuation events, 68 699 deaths and 6152 incident ESKD events. Discontinuation of ACEI/ARB was associated with a higher risk of death [hazard ratio (HR) 2.3, 2.0, 1.99, 1.92 and 1.74 for those discontinued for 14–30, 31–60, 61–90, 91–180 and &gt;180 days, respectively]. Similar associations were noted between ACEI and ARB discontinuation and ESKD (HR 1.64, 1.47, 1.54, 1.65 and 1.59 for those discontinued for 14–30, 31–60, 61–90, 91–180 and &gt;180 days, respectively). Conclusions In a cohort of predominantly male veterans with CKD Stages 3 and 4, ACEI/ARB discontinuation was independently associated with an increased risk of subsequent death and ESKD. This may be due to the severity of illness factors that drive the decision to discontinue therapy. Further investigations to determine the causes of discontinuations and to provide an evidence base for discontinuation decisions are needed.

scholarly journals A cohort study of the relationship between anaemia, mean corpuscular volume and mortality among a CKD population in South Africa

2021 ◽  
Vol 21 (4) ◽  
pp. 1764-75
Author(s):  
Aishatu Nalado ◽  
Bala Waziri ◽  
Gbenga Olorunfemi ◽  
Johnny Mahlangu ◽  
Graham Paget ◽  
...  
Keyword(s):  
South Africa ◽  
Chronic Kidney Disease ◽  
Cohort Study ◽  
Kidney Disease ◽  
Clinical Information ◽  
Tertiary Hospital ◽  
Severe Anaemia ◽  
Factors Affecting ◽  
Risk Of Death ◽  
Increased Risk

Background: The burden of chronic kidney disease is increasing globally and prompt identification, coupled with improved management of CKD patients have increased the population of pre-dialysis patients. We, therefore, aimed to evaluate the predictors of survival among pre-dialysis CKD patients in South Africa. Methods: We conducted a cohort study of 256 consecutive consenting Black non-dialysis requiring CKD patients attending the renal outpatient clinic of a tertiary Hospital in South Africa from 1st June 2016 to 1st December 2016. Socio-demographic and clinical information of the participants were obtained. Descriptive statistics, Kaplan-Meier curves and Cox proportional hazard regression analyses were conducted to evaluate factors affecting the survival of the participants. Results: The mean age of the participants was 52.8±14.3 years and 48.0% were females, 52% were males. The death rate increased with worsening haemoglobin level from 0.96 among patients with mild anaemia to 4.29 per 100-person years among patients with severe anaemia. Anaemic patients with GFR < 30mls/min had significantly increased risk of death (HR 11.51, 95% CI 1.62–78.32, P < 0.001). Conclusion: Mortality in pre-dialysis CKD patients was associated with anaemia and hyperphosphatemia. Clinical interventions targeted at preventing these conditions may improve outcomes among this group of CKD patients. Keywords: Chronic kidney disease; mortality anaemia; outcomes, survival.

scholarly journals Experience with Cinacalcet for Secondary Hyperparathyroidism in Patients with Chronic Kidney Disease Stage III and IV

2009 ◽  
Vol 1 ◽  
pp. CMT.S2983 ◽  
Author(s):  
Terje Forslund ◽  
Arvo Koistinen ◽  
Marja Miettinen
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Secondary Hyperparathyroidism ◽  
Chronic Kidney Disease Stage ◽  
Stage Iii ◽  
Disease Stage ◽  
Phosphate Binders ◽  
Increased Risk ◽  
Ckd Stage ◽  
Patient Reported

Dysequilibrium in calcium and phosphate metabolism with development of secondary hyperparathyroidism (SHPT) is common in patients with chronic kidney disease (CKD) stage III and IV. Dietary phosphate restrictions and calcium based oral phosphate binders have not been effective in all subjects with SHPT, and soft tissue and vascular calcifications with an increased risk of cardiovascular death related are known consequences. Treatment with the calcimimetic Cinacalcet (Cc) has contributed to a better calcium and phosphate control in patients given hemodialysis treatment. In this retrospective study we present our experience with Cc given to ten (one year) or five (two years) patients with CKD stage III and IV and SHPT not suitable for surgery. With conventional therapy target levels of intact parathyroid hormon (iPTH) are seldomly reached the reason why an iPTH value < 300 ng/l was considered acceptable. Levels of iPTH decreased significantly after 3 months of Cc treatment and remained at the lower level. Plasma ionized-Ca (Ca) concentrations decreased initially but remained above 1.00 mmol/l in all but one patient. Phophate (P) levels increased to 1.41 ± 0.09 mmol/l (mean ± SE) leaving the Ca × P product unchanged. While patients with high iPTH needed high Cc doses up to 90 mg/day, some of the patients required very low doses 4.5-20 mg/day in order to achieve a decrease in iPTH levels. Only one patient reported gastric pain needing dose reduction and other adverse effects were not found. No changes in QT-time were observed. We experienced that Cc treatment was promising to control SHPT and stabilized the Ca-P balance in patients with CKD stage III and IV. Dosing may be challenging and laboratory values should be controlled often (monthly) as these patients may have variable response to Cc treatment. Due to the minimal knowledge about its effect on morbidity and mortality in the predialytic population further controlled studies are needed to confirm its efficacy and safety.

scholarly journals High hemoglobin is associated with increased in-hospital death in patients with chronic obstructive pulmonary disease and chronic kidney disease: a retrospective multicenter population-based study

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Libin Xu ◽  
◽  
Yuanhan Chen ◽  
Zhen Xie ◽  
Qiang He ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Hospital Mortality ◽  
Population Based ◽  
Hospital Death ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Risk Of Death ◽  
Increased Risk

Abstract Background Chronic kidney disease (CKD) is a common comorbidity of chronic obstructive pulmonary disease (COPD). Although high hemoglobin (Hb) is detrimental to CKD patients, its relationship with poor outcomes in the COPD population has not been reported. This study aimed to investigate the relationship between high Hb and in-hospital mortality and to explore reference Hb intervals in patients with COPD and CKD. Methods This retrospective study was multicenter population-based. A total of 47,209 patients who presented with COPD between January 2012 and December 2016 were included. The average Hb level during hospitalization was used as the Hb level. CKD and advanced CKD were defined as estimated glomerular filtration rates < 60 and < 30 ml/min/1.73 m2, respectively. The association between Hb level (measured in 1 g/dL intervals) and in-hospital mortality was analyzed in different multivariable logistic regression models by CKD stratification. Results The Hb level was decreased in the CKD subgroup. In the non-CKD group, a higher Hb level was not associated with an increased risk of in-hospital death. However, the Hb level and mortality showed a U-shaped relationship in the CKD group. After adjusting for age and Charlson Comorbidity Index, multivariable regression analysis showed that an Hb level > 17 g/dL was associated with an increased risk of death in the CKD group with an odds ratio (OR) of 2.085 (95% CI, 1.019–4.264). Hb > 14 g/dL was related to an increased risk of death in advanced CKD patients (OR, 4.579 (95% CI, 1.243–16.866)). Conclusions High Hb is associated with an increased risk of in-hospital death in COPD patients with CKD, especially among those with advanced CKD. In this group of patients, attention should be paid to those with high Hb levels.

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