Effects of Elobixibat on Constipation and Lipid Metabolism in Patients With Moderate to End-Stage Chronic Kidney Disease

Objective:The aim of this study was to investigate the effects of elobixibat on constipation and lipid metabolism; and determine the factors associated with the effect of elobixibat on constipation in patients with moderate to end-stage chronic kidney disease (CKD).Methods:Stool frequency and serum lipid parameters were retrospectively analyzed before and after 4 weeks of elobixibat administration in 42 patients (CKD stage G3, 6; stage G4, 9; stage G5, 9; stage G5D, 18). Relationships between the change in stool frequency after initiation of elobixibat and various clinical parameters were analyzed by using linear regression analysis.Results:Elobixibat increased stool frequency from 0.5 ± 0.4 per day to 1.1 ± 0.6 per day (p < 0.001) regardless of whether patients were undergoing dialysis, on concomitant laxatives, or were administered elobixibat before or after breakfast. Elobixibat reduced low-density lipoprotein cholesterol concentration (from 90.9 ± 37.2 mg/dL to 77.5 ± 34.8 mg/dL, p < 0.05) and increased high-density lipoprotein cholesterol concentration (from 44.9 ± 14.3 mg/dL to 57.0 ± 25.8 mg/dL, p < 0.05), but did not change triglyceride concentration. Adverse effects were observed in two patients (nausea and diarrhea). Only phosphate concentration was correlated with the change in stool frequency after initiation of elobixibat (standard coefficient = 0.321, p = 0.043).Conclusions:Elobixibat improved constipation and lipid metabolism in patients with moderate to end-stage CKD, without serious adverse events.

Direct Determination rather than Oscillometric Estimation of Systolic Blood Pressure in Patients with Severe Chronic Kidney Disease

<b><i>Introduction:</i></b> Although arterial hypertension is a major concern in patients with chronic kidney disease (CKD), obtaining accurate systolic blood pressure (SBP) measurement is challenging in this population for whom automatic oscillometric devices may yield erroneous results. <b><i>Methods:</i></b> This cross-sectional study was conducted in 89 patients with stages 4, 5, and 5D CKD, for whom we compared SBP values obtained by the recently described systolic foot-to-apex time interval (SFATI) technique which provides direct SBP determination, the standard technique (Korotkoff sounds), and oscillometry. We investigated the effects of age, sex, diabetes, CKD stage, and pulse pressure to explain measurement errors defined as biases or misclassification relative to the SBP thresholds of 110–130-mm Hg. <b><i>Results:</i></b> All 3 techniques showed satisfactory reproducibility for SBP measurement (CCC &#x3e; 0.84 and &#x3e;0.91, respectively, in dialyzed and nondialyzed patients). The mean ± SD from SBP as determined via Korotkoff sounds was 1.7 ± 4.6 mm Hg for SFATI (CCC = 0.98) and 5.9 ± 9.3 mm Hg for oscillometry (CCC = 0.88). Referring to the 110–130-mm Hg SBP range outside which treatment prescription or adaptation is recommended for CKD patients, SFATI underestimated SBP in 3 patients and overestimated it in 1, whereas oscillometry underestimated SBP in 12 patients and overestimated it in 3. Higher pulse pressure was the main explanatory factor for measurement and classification errors. <b><i>Discussion/Conclusion:</i></b> SFATI provides accurate SBP measurements in patients with severe CKD and paves the way for the standardization of automated noninvasive blood pressure measurement devices. Before prescribing or adjusting antihypertensive therapy, physicians should be aware of the risk of misclassification when using oscillometry.

Ticagrelor vs. Clopidogrel in Acute Coronary Syndrome Patients With Chronic Kidney Disease After New-Generation Drug-Eluting Stent Implantation

Background: The impact of ticagrelor-based dual antiplatelet therapy (DAPT) on acute coronary syndrome (ACS) in patients with chronic kidney disease (CKD) remains unclear.Methods: Data on a total of 1,067 ACS patients with CKD including end-stage renal disease (ESRD) who underwent new-generation drug-eluting stent implantation were extracted from a multicenter registry. This study aimed to compare outcomes of patients treated with ticagrelor- (n = 449) and those treated with clopidogrel-based (n = 618) DAPT. Outcomes of interest included major adverse cardiac and cerebrovascular events (MACCEs) and bleeding (Bleeding Academic Research Consortium grade 3 or 5) at 12 months. Propensity-score matching (346 pairs) analysis was performed.Results: The patients with ESRD showed the highest MACCE and bleeding rates (P &lt; 0.001). There was no difference in the rate of MACCEs between the treatment groups (7.8% vs. 8.4%; hazard ratio [HR] = 0.95, 95% confidence interval [CI] = 0.56–1.61, P = 0.855); however, a trend toward an increased bleeding rate was observed in the ticagrelor-based DAPT group (6.8% vs. 3.8%, HR = 1.84, 95% CI = 0.93–3.63, P = 0.079). Among patients with CKD stage III/IV but without ESRD (277 pairs), the ticagrelor-based DAPT group showed a reduced MACCE rate (3.6% vs. 8.7%, HR = 0.41, 95% CI = 0.19–0.86, P = 0.018) and a similar bleeding rate (5.1% vs. 3.2%, HR = 1.61, 95% CI = 0.70–3.71, P = 0.267), compared with those of the clopidogrel-based DAPT group.Conclusion: The effects of ticagrelor-based DAPT on ischemic and bleeding outcomes of ACS patients with CKD varied according to CKD stage; in ACS patients with CKD without ESRD, ticagrelor-based DAPT reduced MACCE risk without increasing bleeding risks, relative to those observed with clopidogrel-based DAPT.

Initiation of hemodialysis at one month following fistulogram in patients with advanced kidney disease

Objective Previous studies have demonstrated that low contrast volume used in access-related interventions had limited effects on the progression of chronic kidney disease (CKD) after fistulography, but studies are limited and heterogeneous. We sought to evaluate the rate of and factors associated with progression to dialysis (HD) within 1 month after fistulography for patients with advanced CKD. Methods A single-institution retrospective cohort analysis of patients with CKD stage IV and V, not yet on HD, undergoing fistulography from 1 January 2014 to 31 December 2018 was performed. The primary outcome was progression to HD within 1 month. Additional variables and the association with the primary outcome such as medical comorbidities, contrast type or volume were assessed. Results A total of 34 patients underwent 41 fistulograms prior to HD initiation. Progression to HD within 1 month of fistulogram occurred in seven patients (all CKD V). The mean time between fistulogram and HD was 271 days for 31 of 34 patients who ultimately progressed to HD. Those with CKD IV began HD in 549 days on average, while those with CKD V began HD in 190 days on average. Three patients had not initiated HD at a mean of 539 days of follow-up. The only factors associated with progression to HD within 1 month included use of isovue ( p = .005) and elevated contrast volume, with a mean of 40 mL ( p = .027). Conclusion Although none of the patients with CKD IV required HD within 1 month after fistulogram, the use of larger iodinated contrast volume was associated with progression to HD within 1 month of fistulography for patients with CKD V. Further studies should investigate the safety of iodinated and alternative (e.g., carbon dioxide) contrast media in fistulography or duplex-based HD access procedures for CKD patients, especially CKD V, not yet on HD.

Development of a New Smartphone Application to Increase Dietary Compliance in Patients with Chronic Kidney Disease

Aim: Nutritional therapy in chronic kidney disease (CKD) requires certain regulations in the diet of the patients. Patients’ self-management becomes possible with the development of mobile phones and their software. In the current study, a smartphone application that could be used to increase dietary compliance of CKD stage 4-5 and hemodialysis patients was developed. It is aimed that patients can control the dietary intake of energy, protein, sodium, potassium, phosphorus, and fluid by using the developed mobile application. Subjects and Method: The mobile application has been developed by the researchers until the final control and test phase. Later, the final control and test phase of the developed application were carried out by 5 expert dietitians, 5 specialist doctors, and 5 hemodialysis patients. Results: The majority of the participants stated that the application was easy to use, interesting, visually well designed, contains sufficient reliable information, and that they can recommend it to other patients. Participants who examined the application also offered suggestions about the application. Conclusion: The application was updated according to the evaluations and suggestions of the participants. The final application was formed to be ready for the use of the patients.

The Association of Toxoplasma gondii IgG Antibody and Chronic Kidney Disease Biomarkers

Background: Toxoplasma gondii (T. gondii) is a parasite that infects more than 40 million Americans and causes toxoplasmosis. Most cases of toxoplasmosis are asymptomatic; however, T. gondii is capable of invading organs like the kidney, causing chronic infections and cell destruction. Methods: This study focused on evaluating the association between T. gondii exposure and chronic kidney disease (CKD) using data from the 2009–2010 National Health and Nutrition Examination Survey (NHANES). T. gondii exposure was assessed using Toxoplasma gondii IgG antibody status, and the status of CKD was assessed using the CKD biomarkers. The evaluation of risk rate and population prevalence was performed. In addition, multivariable regression models were used to further investigate this association after adjusting for sociodemographic, anthropometric, behavioral, and clinical covariates commonly associated with kidney dysfunction. Results: The positive T. gondii IgG antibody participants had significantly higher levels of CKD biomarkers, including second albumin-to-creatinine ratio (p = 0.0376), second albuminuria (p = 0.0005), and persistent albuminuria (p < 0.0001) compared to the negative participants. Furthermore, there were statistical associations between T. gondii exposure and the status of CKD (negative vs. positive) (p = 0.0001), and between T. gondii exposure and the CKD stage (negative, stage 1, …, stage 5) (p = 0.0004). Without adjusting for age, the positive T. gondii participants had a significantly higher risk (27% higher) of having CKD than the negative participants (RRcrude = 1.27, 95% CI: 1.09–1.49). The age-adjusted prevalence of CKD was higher among Toxoplasma-positive participants compared to the Toxoplasma-negative participants (10.45 vs. 8.99). T. gondii infection was significantly associated with CKD (OR = 1.40, 95% CI = 1.06–1.84, p = 0.00447) after adjusting for age, gender, race/ethnicity, and BMI. Age was positively associated with CKD (OR = 8.89, 95% CI = 6.31–12.51, p < 0.0001) with the participants 45+ years old being 8.89 times more likely to have CKD than those who are <45 years old, after adjusting for T. gondii infection, gender, race/ethnicity, and BMI. Moreover, positive T. gondii increased the odds of CKD progression (OR = 1.41, 95% CI = 1.07–1.86, p = 0.0424). Conclusions: Positive T. gondii IgG antibody is associated with CKD and the progression of CKD stages. This association is more apparent among older people. Further investigations are needed to examine these findings in different geographical locations and among differentially exposed populations.

[68 Ga]Ga-FAPI uptake correlates with the state of chronic kidney disease

Purpose Kidney fibrosis leads to a progressive reduction in kidney function ultimately resulting in kidney failure. Diagnostic tools to detect kidney fibrosis are all invasive in nature requiring kidney biopsies with subsequent histological validation. In this retrospective study, the diagnostic value of three different radiotracers for the noninvasive prediction of kidney fibrosis was analyzed, taking into account the glomerular filtration rate (GFR) and the intra-renal parenchymal radiotracer uptake. Methods In 81 patients receiving either one of the following molecular imaging probes, [68 Ga]Ga-FAPI, [68 Ga]Ga-PSMA, or [68 Ga]Ga-DOTATOC, kidney function parameters were correlated with SUVmax and SUVmean of the renal parenchyma and background activity measured in lung parenchyma, myocardium, gluteal muscle, and the abdominal aorta. Patients were clustered according to their grade of chronic kidney disease (CKD), and a regression analysis and one-way ANOVA were conducted in this retrospective analysis. Results We found a negative correlation between GFR and [68 Ga]Ga-FAPI uptake for both SUVmax and SUVmean values, whereas background activity showed no correlation with GFR. [68 Ga]Ga-DOTATOC and [68 Ga]Ga-PSMA did not correlate between CKD stage and intra-renal parenchymal radiotracer uptake. Only [68 Ga]Ga-PSMA background activity exhibited a positive correlation with GFR suggesting an unspecific binding/retention potentially due to longer circulation times. Conclusion There is a significant negative correlation between renal parenchymal [68 Ga]Ga-FAPI uptake and GFR, which was not the case for [68 Ga]Ga-DOTATOC and [68 Ga]Ga-PSMA. This correlation suggests a specific binding of FAPI rather than a potential unspecific retention in the renal parenchyma, underlining the potential value of [68 Ga]Ga-FAPI for the noninvasive quantitative evaluation of kidney fibrosis.

Cardiovascular disease protein biomarkers are associated with kidney function: the Framingham Heart Study

Background. Biomarkers common to chronic kidney disease (CKD) and cardiovascular disease (CVD) may reflect early impairments underlying both diseases. Methods. We evaluated associations of 71 CVD-related plasma proteins measured in 2,873 Framingham Heart Study (FHS) Offspring cohort participants with cross-sectional continuous eGFR and with longitudinal change in eGFR from baseline to follow-up (ΔeGFR). We also evaluated the associations of the 71 CVD proteins with the following dichotomous secondary outcomes: prevalent CKD stage ≥3(cross-sectional), new-onset CKD stage ≥3 (longitudinal), and rapid decline in eGFR (longitudinal). Proteins significantly associated with eGFR and ΔeGFR were subsequently validated in 3,951 FHS Third Generation cohort participants and were tested using Mendelian randomization (MR) analysis to infer putatively causal relations between plasma protein biomarkers and kidney function. Results. In cross-sectional analysis, 37 protein biomarkers were significantly associated with eGFR at FDR<0.05 in the FHS Offspring cohort and 20 of these validated in the FHS Third Generation cohort at p<0.05/37. In longitudinal analysis, 27 protein biomarkers were significantly associated with ΔeGFR at FDR<0.05 and 12 of these were validated in the FHS Third Generation cohort at p<0.05/27. Additionally, 35 protein biomarkers were significantly associated with prevalent CKD, five were significantly associated with new-onset CKD, and 17 were significantly associated with rapid decline in eGFR. MR suggested putatively causal relations of melanoma cell adhesion molecule (MCAM; -0.011±0.003 mL/min/1.73m2, p=5.11E-5) and epidermal growth factor-containing fibulin-like extracellular matrix protein 1 (EFEMP1; -0.006±0.002 mL/min/1.73m2, p=0.0001) concentration with eGFR. Discussion/Conclusions: Eight protein biomarkers were consistently associated with eGFR in cross-sectional and longitudinal analysis in both cohorts and may capture early kidney impairment; others were implicated in association and causal inference analyses. A subset of CVD protein biomarkers may contribute causally to the pathogenesis of kidney impairment and should be studied as targets for CKD treatment and early prevention.

Menstrual Abnormalities and Associated Hormone Profile In Chronic Kidney Disease Stage 5 Patients

Background: Although menstrual abnormalities and associated hormonal dysregulations are very common in the reproductive age group of Chronic Kidney Disease (CKD) patients, this remains a neglected area. This field had been poorly explored in last ten years worldwide and a few research regarding this area in Bangladesh as well. Aim: To evaluate menstrual abnormalities occurring in CKD stage 5 (CKD5)patients undergoing twice-weekly and thriceweekly maintenance hemodialysis (HD) also in non-dialytic CKD5 patients and to provide more detail information on hormone profile (FSH, LH, Prolactin, Estradiol) of these patients. Materials and method: This obsevational study was conducted in the Department of Nephrology, DMCH, the sample population was also collected from BSMMU and NIKDU from April 2017 to March 2018. A total of 51 CKD stage 5 patients were enrolled in this study. Among them, 34 patients were dialytic (17 of them were taking twice weekly HD and 17 of them were taking thrice weekly HD) and 17 non-dialytic patients at reproductive age were evaluated. Detailed menstrual histories, thorough clinical examinations as well as investigations were done in all the patients. Serum FSH, LH, Estradiol, and Prolactin were evaluated using chemiluminescence immunoassay in the Department of Microbiology of BSMMU. Statistical analysis of the study was done by SPSS-24. The confidence interval was considered at 95% level. P-value <0.05 was considered statistically significant. Results: 100% of non-dialytic CKD5 women had menstrual disorders (72% of patients had secondary amenorrhea, 18% had oligomenorrhoea and 10% had menometrorrhagia). And 73.52% of patients in the HD group had menstrual disorders (29% patients had regular menstruation, 28.5% had secondary amenorrhea, 23.5% had oligomenorrhoea and 19% had menometrorrhagia). With continuation of HD amenorrhea disappeared in 43% of patients in the thrice-weekly HD group, also 22.22% patients in the twice-weekly HD group regained menstruation. Serum LH and prolactin levels were significantly higher in the non-HD group compared to the HD group (p<0.05). Estradiol levels were also higher in HD patients than the non-HD patients. LH and Prolactin levels were also higher in the twice-weekly HD group compared to the thrice-weekly HD group. In the secondary amenorrheic group, serum FSH, LH, Prolactin levels were significantly higher than the other groups having menstrual disorder (p<0.05). Conclusion: Menstrual abnormalities and associated hormonal dysregulations were significantly lower in thriceweekly HD patients compared to the twice-weekly HD patients and significantly lower in twice-weekly HD patients compared to the non-dialytic CKD5 patients. Besides, it is suggested that long-duration dialysis might improve menstrual disorders in such patients as prolactin, LH levels gradually decreased with longer duration of dialysis. J Bangladesh Coll Phys Surg 2022; 40: 45-51

Association Between Sensorineural Hearing Loss and Various Stages of Chronic Kidney Disease

Objectives To compare the proportion of sensorineural hearing impairment (SHI) among patients of chronic kidney disease (CKD) stages 3&4 with CKD stage 5. Materials and Methods This is a cross-sectional study of 30 patients with CKD stages 3 and 4 and 30 patients in stage 5. All patients had an audiological evaluation with pure tone audiometry. Results Our study had 49 males (82%) and 11 females (18%), with the age ranging from 20 to 60 years (mean: 45.13 years). The mean SHI values in stage 3&4 were 28.44 dB and in CKD stage 5 was 31.22 dB. In the right ear, the mean hearing loss in stage 3, stage 4, and stage 5 was 28.17 dB, 28.67 dB, and 31.84 dB, respectively. In the left ear, the mean SHI values in stage 3, stage 4, and stage 5 were 27.05 dB, 31.89 dB, and 30.61 dB, respectively.The mean SHI in stage 3&4 for age group 20 to 30 years was 13.66 dB, for 31 to 40 years was 26.33 dB, for 41 to 50 years was 35.18 dB, for 51 to 60 years was 37.12 dB. The mean SHI in stage 5 for the age group of 20 to 30 years was 16.48 dB, for 31 to 40 years was 28.29 dB, for 41 to 50 years was 31.82 dB, for 51 to 60 years was 34.35 dB. There was a significant correlation between hearing loss and CKD with respect to age (p < 0.001). The duration of renal illness and associated comorbidities was not a significant contributor to hearing loss in our study (p > 0.05). Conclusion As per our study, with progression in the stage of chronic kidney disease, the hearing loss also increased indicating a possible link between the two. We also noted that the hearing loss increased with the increasing age.