Operations Research to Solve Kidney Allocation Problems: A Systematic Review

Background: Operations research techniques enable health care administrators to optimize resource allocation and to find solutions to staff and patient scheduling problems. We aimed to conduct the first systematic review of the international literature on the use of operations research for allocating deceased-donor kidneys. Methods: We searched the MEDLINE, EMBASE, and PubMed databases from inception to February 2023. Two reviewers independently screened the title/abstract and subsequently the full text of potentially eligible articles and abstracted the data. Quality assessment of the final set of studies was conducted using Subben’s checklist. Results: Of the 302 citations identified, 5 studies were included. These studies covered three themes, including (1) provider-facing decision aids to determine the timing of transplant for single or multiple patients; (2) system-level planning on kidney allocation based on blood type matching rules; and (3) patient-facilitated wait times estimation using incomplete information. Markov models, sequential stochastic assignment models, and queuing models were amongst the most used techniques. Although we found all included studies to meet Subben’s criteria, we believe the checklist in its current form lacks items to assess the validity of model inferences. As such, we ended this review with a set of practical recommendations. Conclusions: Our review demonstrated the utility of operations research techniques in assisting the system, healthcare providers, and patients in the transplantation process. More research is needed to reach a consensus on a model that can be used to support the decision-making of different stakeholders for efficient kidney allocation, with the ultimate goal of reducing the gap between kidney supply and demand and enhancing the population’s well-being

Sleep quality, depression, and quality of life in patients with chronic kidney disease: a single centre experience

Background: Sleeping problems and depression are more common in patients with chronic kidney disease (CKD) than the general population. The primary objective of this cross-sectional study was to test factors associated with sleep disturbances, depression, and quality of life among patients with CKD. Methods: We recruited patients with CKD who lived in the St. John’s area from September 2012 to December 2012. The Pittsburgh Sleep Quality Index (PSQI), the Berlin Questionnaire (BQ), the Beck Depression Inventory (BDI), the Beck Depression Inventory Fast-Screen for Medical Patients (BDI-FS), and the Short Form 36 Quality of Life Health Survey Questions (SF-36) were administered to all participants. A chart review was performed for the patients’ demographics, diagnoses, medication lists, and certain laboratory parameters—including blood glucose, hemoglobin, albumin, calcium, phosphate, parathyroid hormone, and estimated glomerular filtration rate (e-GFR). Logistic regression models were employed to estimate odds ratios (OR) with 95% confidence intervals (CI). Results: The sample had a total of 303 patients (41% female and 99% Caucasian). One hundred and seventeen (39%) patients were labeled as poor sleepers with the PSQI, while 157 (51.8%) patients had high risk for sleep apnea in the study cohort. Physical component scores (PCS) and mental component scores (MCS) of the SF-36 questionnaire were significantly lower in the dialysis group when compared to the non-dialysis group. iii A higher risk for impaired sleep was associated with being a female and on antidepressants and/or benzodiazepine or non-benzodiazepine hypnotic agents. Conclusions: Sleep problems and depression are common in kidney patients. Women are more prone to sleeping problems than their male counter-parts. Furthermore, people who have low MCS scores are more prone to impaired sleep or vice versa

PROCALCITONIN AND MALONDIALDEHYDE AS MARKERS OF INFLAMMATION IN HEMODIALYSIS PATIENTS

Aim: Procalcitonin (PCT) is known as an infection marker. Malondialdehyde (MDA) is considered as a marker of oxidative stress. Both have been found to be elevated in peritoneal dialysis patients. In this study, we measured procalcitonin, malondialdehyde, and traditional inflammation markers, including albumin, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), fibrinogen, lymphocyte counts, and white blood cell counts (WBC) in hemodialysis (HD) patients, patients with moderate chronic kidney disease (CKD), and healthy subjects. Material and Method: We measured PCT, MDA, albumin, CRP, ESR, fibrinogen, lymphocyte counts, and WBC in 35 maintenance HD patients, 30 patients with moderate chronic kidney disease and a control group with normal kidney functions. The correlation of PCT and MDA with traditional inflammation markers (albumin, CRP, ESR, fibrinogen, lymphocyte counts, and WBC) was also evaluated. Results: PCT levels were significantly higher and were correlated with CRP levels in the HD group (r=0.89). MDA was significantly higher in HD patients and non-dialysis CKD patients as compared to healthy controls. Discussion: Higher PCT levels in HD patients might be caused by minimal endotoxin contamination. Elevated CRP levels, known as a marker of inflammation, were correlated with elevated PCT levels. PCT may also be a marker of inflammation

Assessment of DNA Oxidation and Antioxidant Activity in Hypertensive Patients with Chronic Kidney Disease

The aim of this study was to evaluate the oxidative DNA damage, antioxidant activity, and effects of antihypertensive drugs on oxidative stress in hypertensive patients with different stages of chronic kidney disease (CKD). Fifty-three non-dialyzed hypertensive CKD patients were included by the study. Serum and urinary 8-hydroxydeoxy guanosine (8-OHdG) levels (as a marker of oxidative DNA damage), serum superoxide dismutase (SOD), and glutathione peroxidase (G-Px) activities (as antioxidant enzymes) were measured. SOD activity was higher and G-Px activity was lower in the patient group as compared to control group. Serum and urinary 8-OHdG levels were found to be higher in the patients with proteinuria greater than 3 g/day than those in the patients with proteinuria less than 3 g/day. It has been determined that G-Px activity and urinary 8-OHdG level were lower in the patients treated with angiotensin-converting enzyme (ACE) inhibitor compared to patients treated with calcium channel blocker. The present data show oxidative DNA damage at a higher level in the patients with proteinuria greater than 3 g/day. In comparison to a calcium channel blocker, an ACE inhibitor seems much more protective against oxidative DNA damage in hypertensive patients with different stages of CKD

Effects of different phosphate lowering strategies in patients with CKD on laboratory outcomes: A systematic review and NMA

<div><p>Background</p><p>Chronic kidney disease-mineral and bone disorder (CKD-MBD), a complication of chronic kidney disease, has been linked to reduced quality and length of life. High serum phosphate levels that result from CKD-MBD require phosphate-lowering agents, also known as phosphate binders. The objective of this systematic review is to compare the effects of available phosphate binders on laboratory outcomes in patients with CKD-MBD.</p><p>Methods</p><p>Data sources included MEDLINE and EMBASE from January 1996 to April 2016, and the Cochrane Register of Controlled Trials up to April 2016. Teams of two reviewers, independently and in duplicate, screened titles and abstracts and potentially eligible full text reports to determine eligibility, and subsequently abstracted data and assessed risk of bias in eligible randomized controlled trials (RCTs). Eligible trials enrolled patients with CKD-MBD and randomized them to receive calcium-based phosphate binders (delivered as calcium acetate, calcium citrate or calcium carbonate), non-calcium-based phosphate binders (NCBPB) (sevelamer hydrochloride, sevelamer carbonate, lanthanum carbonate, sucroferric oxyhydroxide and ferric citrate), phosphorus restricted diet (diet), placebo or no treatment and reported effects on serum levels of phosphate, calcium and parathyroid hormone.</p><p>We performed Bayesian network meta-analyses (NMA) to calculate the effect estimates (mean differences) and 95% credible intervals for serum levels of phosphate, calcium and parathyroid hormone. We calculated direct, indirect and network meta-analysis estimates using random-effects models. We applied the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach to rate the quality of evidence for each pairwise comparison.</p><p>Results</p><p>Our search yielded 1108 citations; 71 RCTs were retrieved for full review and 16 proved eligible. Including an additional 13 studies from a previous review, 29 studies that enrolled 8335 participants proved eligible; 26 trials provided data for quantitative synthesis. Sevelamer, lanthanum, calcium, iron, diet and combinations of active treatments (calcium or sevelamer or lanthanum and combination of calcium and sevelamer) resulted in significantly lower serum phosphate as compared to placebo (moderate to very low quality of evidence). We found no statistically significant differences between active treatment categories in lowering serum phosphate. Sevelamer, lanthanum and diet resulted in lower serum calcium compared to calcium (moderate quality evidence for lanthanum and diet; low quality evidence for Sevelamer). Iron, sevelamer and calcium yielded lower parathyroid hormone levels as compared to lanthanum. Meta-regression analyses did not yield a statistically significant association between treatment effect and trial duration.</p><p>Discussion/Conclusions</p><p>We found few differences between treatments in impact on phosphate and differences in parathyroid hormone. Relative to calcium, sevelamer, lanthanum and diet showed significant reduction in serum calcium from baseline. Treatment recommendations should be based on impact on patient-important outcomes rather than on surrogate outcomes.</p><p>Systematic review registration: PROSPERO CRD-42016032945</p></div

Network meta-analysis results for serum parathyroid hormone.

<p>Forest plot of effectiveness outcome for mean parathyroid hormone reduction at the end of the study period; MD: Mean difference; Crl: Credible interval; PrI: predictive interval.</p

Direct, indirect, and NMA estimates of parathyroid hormone with 95% credible intervals and GRADE assessments from each pairwise comparison within the phosphate-binder network.

<p>Direct, indirect, and NMA estimates of parathyroid hormone with 95% credible intervals and GRADE assessments from each pairwise comparison within the phosphate-binder network.</p

Risk of bias assessment for surrogate outcomes.

<p>Risk of bias assessment for surrogate outcomes.</p

Network meta-analysis results for serum calcium.

<p>Forest plot of effectiveness outcome for mean calcium reduction at the end of the study period; MD: Mean difference; Crl: Credible interval; PrI: predictive intervals.</p

Network of clinical trials of phosphate binders in patients with chronic kidney disease: outcome mean change from baseline in serum calcium concentration.

<p>Netplot of effectiveness outcome for mean calcium reduction at the end of the study period. Network of randomized controlled trials comparing different phosphate binders for mean change in serum calcium. Lines connect different phosphate binder categories with direct evidence. The width of lines correlates the number of RCTs for each direct comparison while the size of the nodes correlates with the total sample size. Abbreviations: cal: calcium; calmag: calcium and magnesium; calsev: calcium and Sevelamer; Lant: lanthanum; seve: Sevelamer.</p