Application of regularized regression to identify novel predictors of mortality in a cohort of hemodialysis patients

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.

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INFLAMMATORY MARKERS IN END-STAGE RENAL DISEASE PATIENTS ON HAEMODIALYSIS

Journal of Medical Biochemistry ◽

10.5937/jomb0-26120 ◽

2020 ◽

Author(s):

Phebe Lotfy Abdel-Messeih ◽

Manal Mohamed Alkady ◽

Neveen Mostafa Nosseir ◽

Mohamed Said Tawfik

Keyword(s):

Inflammatory Markers ◽

Glycosylated Hemoglobin ◽

Serum Levels ◽

Hemodialysis Patients ◽

Inflammatory Status ◽

Chemokine Ligand ◽

And Gender ◽

Inorganic Phosphorous ◽

Stage Renal Disease ◽

End Stage

Background: CXC chemokine ligand 16 (CXCL16) is an inflammatory chemokine that mediates renal infiltration of macrophages and activated T cells.Aim: To investigate serum levels of CXCL16 in patients undergoing hemodialysis and their correlation with other inflammatory markers such as C-reactive protein (CRP) and intact parathyroid hormone (iPTH).Methods: The study included 40 hemodialysis patients (22 males) and 40 age and gender-matched controls (24 males). Fasting blood sugar (FBS), urea, creatinine, calcium and inorganic phosphorous were assayed in participants using routine methods, glycosylated hemoglobin (HbA1c) by quantitative chromatographic spectrophoto metry, iPTH by chemiluminescent microparticle immuno assay, CRP by nephelometry and CXCL16 by ELISA technique.Results: Serum CXCL16, CRP, PTH, FBS, urea, and creatinine levels were significantly higher in hemodialysis patients compared to controls (p<0.00001). No statistically significant differences were observed between patients and controls for calcium, phosphorous, and HbA1c. SerumCXCL16 levels correlated positively with CRP (r=0.956, p<0.00001) and iPTH (r=-0.403, p<0.001). Hemodialysis patients (diabetics or hypertensives) had significantly higher CXCL16 levels compared to non-diabetics or nonhypertensives. Conclusions: High levels of serum CXCL16, CRP and iPTH reflect the inflammatory status of hemodialysis patients and help avoid complications. Serum CXCL16 could be used as a biomarker together with CRP in these patients.

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Ghrelin and Obestatin Levels in End-stage Renal Disease

Journal of International Medical Research ◽

10.1177/147323000903700319 ◽

2009 ◽

Vol 37 (3) ◽

pp. 757-765 ◽

Cited By ~ 22

Author(s):

B Aygen ◽

A Dogukan ◽

FE Dursun ◽

S Aydin ◽

N Kilic ◽

...

Keyword(s):

Renal Disease ◽

End Stage Renal Disease ◽

Energy Homeostasis ◽

Serum Levels ◽

Healthy Controls ◽

Stage Renal Disease ◽

End Stage ◽

Study Participants ◽

Serum Ghrelin ◽

Esrd Patients

Malnutrition is fairly common in end-stage renal disease (ESRD) patients, persistent lack of appetite being a major symptom. Ghrelin and obestatin are two hormones that are involved in appetite and energy homeostasis. The present study examined ghrelin and obestatin levels in 24 ESRD patients undergoing haemodialysis and 24 age-matched healthy controls. Serum and saliva ghrelin and obestatin levels in the ESRD patients were significantly higher compared with controls, while saliva ghrelin and obestatin levels in all study participants were significantly higher than serum levels. Saliva ghrelin correlated with serum ghrelin and saliva obestatin correlated with serum obestatin in all study participants, although there was no correlation between ghrelin and obestatin levels. In conclusion, the results suggest that the kidneys may have a role in the metabolism and/or clearance of obestatin, as they do for ghrelin. Further studies are needed to determine if elevated levels of these hormones in ESRD patients contribute to the malnutrition that is common in these patients.

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Parathyroidectomy Versus Cinacalcet for the Treatment of Secondary Hyperparathyroidism in Hemodialysis Patients

World Journal of Surgery ◽

10.1007/s00268-022-06439-7 ◽

2022 ◽

Author(s):

Luis Alvarado ◽

Nishtha Sharma ◽

Roxann Lerma ◽

Alok Dwivedi ◽

Adeel Ahmad ◽

...

Keyword(s):

Propensity Score ◽

Secondary Hyperparathyroidism ◽

Propensity Score Matching ◽

Cox Regression ◽

The United States ◽

Hemodialysis Patients ◽

Cox Regression Analysis ◽

Pathologic Fractures ◽

Stage Renal Disease ◽

End Stage

Abstract Background Secondary hyperparathyroidism in patients with end stage renal disease on dialysis is associated with bone pain and fractures in addition to cardiovascular morbidity. Cinacalcet is the most commonly used drug to treat such patients, but it has never been compared to surgery. The goal of this study is to compare the long-term outcomes and survival between cinacalcet and parathyroidectomy in the treatment of secondary hyperparathyroidism in hemodialysis patients. Methods Adult patients on hemodialysis who were treated with cinacalcet or parathyroidectomy in the United States Renal Data System were included. Patients treated with surgery (n = 2023) were compared using 1:1 propensity score matching ratio to a cohort of patients treated with cinacalcet. A Cox regression analysis was conducted to compare the overall mortality. Results The propensity score matching successfully created two groups with similar demographics. Patients in the surgery group had a higher mean peak PTH level prior to therapy (2066.8 vs 1425.4, P < 0.001). No difference was observed in the development of new-onset coronary artery disease (7.7% vs 7.9%, P = 0.8) or cerebrovascular disease (7% vs 6.7%, P = 0.8). Surgical patients had a higher rate of pathologic fractures (27.8% vs 24.9%, P = 0.04). Survival analysis showed that patients undergoing surgery had a better 5-year survival (65.6% vs 57.8%) and were less likely to die within the study period (HR 0.77, 95% CI 0.7–0.85, P < 0.0001). Conclusions Patients on dialysis undergoing parathyroidectomy for the treatment of secondary hyperparathyroidism have a better overall survival than those treated with cinacalcet.

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THE IMPACT OF VIT-D ON SURVIVAL IN HEMODIALYSIS PATIENTS: A CRITICAL APPRAISAL

Journal of medical pharmaceutical and allied sciences ◽

10.22270/jmpas.v10i4.1198 ◽

2021 ◽

Vol 10 (4) ◽

pp. 3359-3362

Author(s):

Monali Rajendrakumar Sahu

Keyword(s):

Side Effects ◽

Racial Differences ◽

Controlled Trial ◽

Serum Levels ◽

Hemodialysis Patients ◽

Non Invasive ◽

Specific Mortality ◽

Stage Renal Disease ◽

End Stage ◽

The Impact

Vit-D deficiency (20 ng / mL) and deficiency (20-29 ng / mL) are common side effects in people with chronic disease V or End stage Renal Disease on dialysis. In addition to the lack of exposure to nutrients and sun, reduced Vit-D and body composition, obesity, and racial differences also play a role. In addition, due to a deficiency of 25 (OH) D, serum levels of 1, 25 (OH) 2D decreased over time in CKD patients, as well as non-invasive detection of 25 (OH) D by associated renal cells, increased fibroblast factor -23, and a decrease in functional tissue. Vit-D deficiency causes secondary hyperparathyroidism and associated side effects, such as high hyperparathyroidism and hypercalcemia, requiring surgical parathyroidectomy or the use of calcimimetics. This document examines the available evidence and underscores the importance of Vit-D supplementation in hemodialysis patients. To assess the strength and critically review the available evidence on impact of Vit-D in survival of hemodialysis patients. Vit-D has a survival advantage in patients with CKD-MBD, however we need randomized controlled trial in hemodialysis patients with matched controls given placebo, to prove benefits of Vit-D in terms of all cause and cause specific mortality.

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Vasculitis ANCA: Alternativas de tratamiento y las expectativas en los pacientes

Karger Kompass Neumología ◽

10.1159/000513798 ◽

2021 ◽

pp. 1-2

Author(s):

Carolina Aguilar-Martínez

Keyword(s):

Systematic Review ◽

Cox Regression ◽

Meta Analysis ◽

Significant Risk ◽

Limiting Factor ◽

Significant Survival ◽

Stage Renal Disease ◽

End Stage ◽

Immunosuppression Therapy

Background: The benefits of treating anti-neutrophil cytoplasmic autoantibody-associated vasculitis (AAV) in advancing age remains unclear with most published studies defining elderly as ≥65 years. This study aims to determine outcomes of induction immunosuppression in patients aged ≥75 years. Methods: A cohort of patients aged ≥75 years with a diagnosis of AAV between 2006 and 2018 was constructed from 2 centres. Follow-up was to 2 years or death. Analysis included multivariable Cox regression to compare mortality and end-stage renal disease (ESRD) based on receipt of induction immunosuppression therapy with either cyclophosphamide or rituximab. A systematic review of outcome studies was subsequently undertaken amongst this patient group through Pubmed, Cochrane and Embase databases from inception until October 16, 2019. Results: Sixty-seven patients were identified. Mean age was 79 ± 2.9 years and 82% (n = 55) received induction immunosuppression. Following systematic review, 4 studies were eligible for inclusion, yielding a combined total of 290 patients inclusive of our cohort. The aggregated 1-year mortality irrespective of treatment was 31% (95% CI 25–36%). Within our cohort, induction immunosuppression therapy was associated with a significantly lower 2-year mortality risk (hazard ratio [HR] 0.29 [95% CI 0.09–0.93]). The pooled HR by meta-analysis confirmed this with a significant risk reduction for death (HR 0.31 [95% CI 0.16–0.57], I2 = 0%). Treated patients had a lower pooled rate of ESRD, but was not statistically significant (HR 0.71 [95% CI 0.15–3.35]). Conclusion: This meta-analysis suggests that patients ≥75 years with AAV do benefit from induction immunosuppression with a significant survival benefit. Age alone should not be a limiting factor when considering treatment.

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Real-world evidence and optimization of vocal dysfunction in end-stage renal disease patients with secondary hyperparathyroidism

Scientific Reports ◽

10.1038/s41598-020-79810-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Geng-He Chang ◽

Fong-Fu Chou ◽

Ming-Shao Tsai ◽

Yao-Te Tsai ◽

Ming-Yu Yang ◽

...

Keyword(s):

Renal Disease ◽

Secondary Hyperparathyroidism ◽

Real World ◽

End Stage Renal Disease ◽

Cox Regression ◽

Electrolyte Imbalance ◽

Research Database ◽

Cox Regression Analysis ◽

Stage Renal Disease ◽

End Stage

AbstractPatients with end-stage renal disease (ESRD) may demonstrate secondary hyperparathyroidism (SHPT), characterized by parathyroid hormone oversecretion in response to electrolyte imbalance (e.g., hypocalcemia and hyperphosphatemia). Moreover, this electrolyte imbalance may affect vocal cord muscle contraction and lead to voice change. Here, we explored the effects of SHPT on the voices of patients with ESRD. We used data of 147,026 patients with ESRD from the registry for catastrophic illness patients, a sub-database of Taiwan National Health Insurance Research Database. We divided these patients into 2 groups based on whether they had hyperparathyroidism (HPT) and compared vocal dysfunction (VD) incidence among them. We also prospectively included 60 ESRD patients with SHPT; 45 of them underwent parathyroidectomy. Preoperatively and postoperatively, voice analysis was used to investigate changes in vocal parameters. In the real-world database analysis, the presence of HPT significantly increased VD incidence in patients with ESRD (p = 0.003): Cox regression analysis results indicated that patients with ESRD had an approximately 1.6-fold increased VD risk (p = 0.003). In the clinical analysis, the “jitter” and “shimmer” factors improved significantly after operation, whereas the aerodynamic factors remained unchanged. In conclusion, SHPT was an independent risk factor for VD in patients with ESRD, mainly affecting their acoustic factors.

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Kidney transplantation in the extremely elderly from extremely aged deceased donors: a kidney for each age

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfz293 ◽

2020 ◽

Vol 35 (4) ◽

pp. 687-696

Author(s):

Jimena Cabrera ◽

Mario Fernández-Ruiz ◽

Hernando Trujillo ◽

Esther González ◽

María Molina ◽

...

Keyword(s):

Kidney Transplantation ◽

Graft Survival ◽

Cox Regression ◽

Patient Survival ◽

Incidence Rates ◽

Allocation Policy ◽

Recipient Age ◽

Deceased Donors ◽

Stage Renal Disease ◽

End Stage

Abstract Background Advances in life expectancy have led to an increase in the number of elderly people with end-stage renal disease (ESRD). Scarce information is available on the outcomes of kidney transplantation (KT) in extremely elderly patients based on an allocation policy prioritizing donor–recipient age matching. Methods We included recipients ≥75 years that underwent KT from similarly aged deceased donors at our institution between 2002 and 2015. Determinants of death-censored graft and patient survival were assessed by Cox regression. Results We included 138 recipients with a median follow-up of 38.8 months. Median (interquartile range) age of recipients and donors was 77.5 (76.3–79.7) and 77.0 years (74.7–79.0), with 22.5% of donors ≥80 years. Primary graft non-function occurred in 8.0% (11/138) of patients. Cumulative incidence rates for post-transplant infection and biopsy-proven acute rejection (BPAR) were 70.3% (97/138) and 15.2% (21/138), respectively. One- and 5-year patient survival were 82.1 and 60.1%, respectively, whereas the corresponding rates for death-censored graft survival were 95.6 and 93.1%. Infection was the leading cause of death (46.0% of fatal cases). The occurrence of BPAR was associated with lower 1-year patient survival [hazard ratio (HR) = 4.21, 95% confidence interval (CI) 1.64–10.82; P = 0.003]. Diabetic nephropathy was the only factor predicting 5-year death-censored graft survival (HR = 4.82, 95% CI 1.08–21.56; P = 0.040). Conclusions ESRD patients ≥75 years can access KT and remain dialysis free for their remaining lifespan by using grafts from extremely aged deceased donors, yielding encouraging results in terms of recipient and graft survival.

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The Profile of Timing Dialysis Initiation in Patients with End-stage Renal Disease in China: A Cohort Study

Kidney & Blood Pressure Research ◽

10.1159/000504671 ◽

2020 ◽

Vol 45 (2) ◽

pp. 180-193

Author(s):

Ying Liu ◽

Luping Wang ◽

Xianfeng Han ◽

Yang Wang ◽

Xuefeng Sun ◽

...

Keyword(s):

Renal Disease ◽

End Stage Renal Disease ◽

Cox Regression ◽

Mainland China ◽

Dialysis Initiation ◽

Significant Difference ◽

Initiation Of Dialysis ◽

Stage Renal Disease ◽

End Stage ◽

The Relationship

Background: Hemodialysis is the main approach for renal replacement therapy in patients with end-stage renal disease (ESRD) in China. The timing of dialysis initiation is one of the key factors influencing patient survival and prognosis. Over the past decade, the relationship between the timing of dialysis initiation and mortality has remained unclear in patients with ESRD in China. Methods: Patients who commenced maintenance hemodialysis from 2009 to 2014 from 24 hemodialysis centers in Mainland China were enrolled in the study (n = 1,674). Patients were divided into 2 groups based on the year they started hemodialysis (patients who started hemodialysis from 2009 to 2011, and patients who started hemodialysis from 2012 to 2014). Analysis of the yearly change in the estimated glomerular filtration rate (eGFR) at the initiation of dialysis was performed for the 2 groups. Meanwhile, the patients were divided into 3 groups based on their eGFR at the initiation of dialysis (<4, 4–8, and >8 mL/min/1.73 m2). For these 3 groups, the relationship between the eGFR at the start of dialysis and mortality were analyzed. Results: The average eGFRs were 5.68 and 5.94 mL/min/1.73 m2 for 2009–2011 and 2012–2014, respectively. Compared with the 2009–2011 group, the proportion of patients with diabetes in 2012–2014 increased from 26.7 to 37.7%. The prognosis of patients with different eGFRs at the start of dialysis was analyzed using Kaplan-Meier survival curves. After adjusting for confounding factors through a Cox regression model, no significant difference was demonstrated among the 3 groups (<4 mL/min/1.73 m2 was used as the reference, in comparison with 4–8 mL/min/1.73 m2 [p = 0.681] and >8 mL/min/1.73 m2 [p = 0.403]). Conclusion: In Mainland China, the eGFR at the start of dialysis did not change significantly over time from 2008 to 2014 and had no association with the mortality of patients with ESRD.

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