Higher sclerostin is associated with pulmonary hypertension in pre-dialysis end-stage kidney disease patients: a cross-sectional prospective observational cohort study.

BACKGROUND: Pulmonary hypertension (PH) is a complication of chronic kidney disease (CKD) that contributes to mortality. Sclerostin, a SOST gene product that reduces osteoblastic bone formation by inhibiting Wnt/ß-catenin signaling, is involved in arterial stiffness and CKD-bone mineral disease, but scanty evidence to PH. This study explored the relationship between sclerostin and PH in CKD 5, pre-dialysis end-stage kidney disease (ESKD) patients. METHODS: This cross-sectional prospective observational cohort study included 44 pre-dialysis ESKD patients between May 2011 and May 2015. Circulating sclerostin levels were measured using an enzyme-linked immunosorbent assay. PH was defined as an estimated pulmonary artery systolic pressure > 35 mmHg on echocardiography. RESULTS: Patients with higher sclerostin levels ≥ 218.18pmol/L had echocardiographic structural cardiac abnormalities, especially PH (P < 0.01). On multivariate logistic analysis, sclerostin over 218.19pmol/L was significantly associated with PH (odds ratio [OR], 41.14; 95% confidence interval [CI], 4.53-373.89, P < 0.01), but multivariate Cox regression analysis showed the systemic vascular calcification score over 1 point (Hazard ratio [HR] 11.49 95% CI 2.48-53.14, P = 0.002) and PH ([HR] 5.47, 95% CI 1.30-23.06, P = 0.02) were risk factors for all-cause mortality in pre-dialysis ESKD patients. CONCLUSIONS: Serum sclerostin and PH have a positive correlation in predialysis ESKD patients. The higher systemic vascular calcification score and PH have an association to increase all-cause mortality in pre-dialysis ESKD patients.

Association between inpatient education program for patients with pre-dialysis chronic kidney disease and new-onset cardiovascular disease after initiating dialysis.

BACKGROUND: The association between inpatient education programs (IEPs) for patients with pre-dialysis chronic kidney disease (CKD) and new-onset cardiovascular disease (CVD) after initiating dialysis is unclear. METHODS: We conducted a retrospective cohort study between January 1, 2011 and December 31, 2018, evaluating CKD patients who were divided into two groups based on whether or not they participated in IEPs. The primary outcome was a new-onset CVD event after initiating dialysis. Cumulative incidence function was used to describe new-onset CVD considering the competing outcome of death. Additionally, Cox proportional hazards models were used to estimate the hazard ratio of new-onset CVD between IEP and non-IEP groups. RESULTS: Of the 493 patients, 131 (26.6%) patients had participated in IEPs. The IEP group had a significantly longer duration of CKD management by nephrologists (median 142 vs. 115 days, P = 0.007), lower rate of emergency hospital admissions (9.9% vs. 27.1%, P < 0.001), better ability to perform activities of daily living (Grade J; 81.6% vs. 69.1%, P = 0.046), higher rate of pre-placement of permanent vascular access or peritoneal dialysis catheters (82.4% vs. 59.4%, P < 0.001), and a higher serum albumin level at the beginning of dialysis (3.5 ± 0.5 vs. 3.3 ± 0.6 g/dL, P < 0.001). The cumulative incidence of new-onset CVD at three years after initiating dialysis in the IEP and non-IEP groups was 16.9% and 22.5%, respectively. The hazard ratio for new-onset CVD after initiating dialysis in the IEP group was 0.63 (95% CI: 0.41-0.97, P = 0.036). CONCLUSION: IEPs were associated with a lower rate of new-onset CVD after initiating dialysis.

Electrocardiographic measurements in children with pre-dialysis chronic kidney disease and undergoing kidney replacement therapy.

Cardiovascular diseases are the main causes of morbidity in children with chronic kidney disease (CKD). Electrocardiography (ECG) can provide important information about cardiac functions and parameters associated with sudden cardiac death. This study aims to evaluate the potentially dangerous changes in CKD and kidney replacement therapies by ECG and to determine the value of ECG in predicting cardiovascular outcome compared with echocardiography. 101 patients with CKD were divided into subgroups according to treatment modalities as pre-dialysis CKD, hemodialysis (HD), peritoneal dialysis (PD) and kidney transplantation (KTx). Differences in anthropometric measurements, laboratory results, blood pressures, ECG monitoring were compared within groups as well as with 40 healthy controls. Available echocardiographic findings were noted. In the patients, HD group had highest frequency of hypertension. ECG revealed prolonged QTc as more frequent (16.8% vs 0%, p = 0.006) and higher QTcD (56.7 ± 6.5 vs 39.9 ± 5.1 ms, p = 0.001) in the patients compared to controls, especially in dialysis patients, whereas lowest values were in KTx subgroup. Left ventricular (LV) hypertrophy (LVH) was more frequent (47.1%) in HD compared to other CKD subgroups in ECG (p = 0.052). Echocardiography also showed LV mass index as highest in HD and lowest in KTx (121.4 ± 55.7 vs 63.7 ± 18.3 g/m2, p = 0.000), with numerically highest LVH in HD (58.3%, p = 0.063).  Conclusion: ECG can be used to detect cardiovascular problems in patients with CKD, especially in HD. As ECG results were in line with echocardiography, patients with ECG abnormalities suggestive of LVH should be referred for echocardiographic assessment. What is Known: • Cardiovascular diseases such as coronary artery disease, congestive heart failure, arrhythmias and sudden cardiac death are major causes of morbidity and mortality in chronic kidney disease. • Electrocardiography has significant advantages in demonstrating cardiac functions in children because it is readily available, non-invasive and often non-experts can interpret the results. What is New: • The heart rate is higher, QTc is longer and QTcD is higher in dialysis patients and the prolonged QTc is more frequent in patients with underlying glomerular diseases. • Left ventricular hypertrophy is more common in HD patients and those with hypertension, hypercalcemia, anemia or glomerular etiology. The cardiovascular risky conditions are less frequent in the patients with kidney transplantation.

Unsupervised clustering identifies sub-phenotypes and reveals novel outcome predictors in patients with dialysis-requiring sepsis-associated acute kidney injury.

INTRODUCTION: Heterogeneity exists in sepsis-associated acute kidney injury (SA-AKI). This study aimed to perform unsupervised consensus clustering in critically ill patients with dialysis-requiring SA-AKI. PATIENTS AND METHODS: This prospective observational cohort study included all septic patients, defined by the Sepsis-3 criteria, with dialysis-requiring SA-AKI in surgical intensive care units in Taiwan between 2009 and 2018. We employed unsupervised consensus clustering based on 23 clinical variables upon initializing renal replacement therapy. Multivariate-adjusted Cox regression models and Fine-Gray sub-distribution hazard models were built to test associations between cluster memberships with mortality and being free of dialysis at 90 days after hospital discharge, respectively. RESULTS: Consensus clustering among 999 enrolled patients identified three sub-phenotypes characterized with distinct clinical manifestations upon renal replacement therapy initiation (n = 352, 396 and 251 in cluster 1, 2 and 3, respectively). They were followed for a median of 48 (interquartile range 9.5-128.5) days. Phenotypic cluster 1, featured by younger age, lower Charlson Comorbidity Index, higher baseline estimated glomerular filtration rate but with higher severity of acute illness was associated with an increased risk of death (adjusted hazard ratio of 3.05 [95% CI, 2.35-3.97]) and less probability to become free of dialysis (adjusted sub-distribution hazard ratio of 0.55 [95% CI, 0.38-0.8]) than cluster 3. By examining distinct features of the sub-phenotypes, we discovered that pre-dialysis hyperlactatemia ≥3.3 mmol/L was an independent outcome predictor. A clinical model developed to determine high-risk sub-phenotype 1 in this cohort (C-static 0.99) can identify a sub-phenotype with high in-hospital mortality risk (adjusted hazard ratio of 1.48 [95% CI, 1.25-1.74]) in another independent multi-centre SA-AKI cohort. CONCLUSIONS: Our data-driven approach suggests sub-phenotypes with clinical relevance in dialysis-requiring SA-AKI and serves an outcome predictor. This strategy represents further development toward precision medicine in the definition of high-risk sub-phenotype in patients with SA-AKI.Key messagesUnsupervised consensus clustering can identify sub-phenotypes of patients with SA-AKI and provide a risk prediction.Examining the features of patient heterogeneity contributes to the discovery of serum lactate levels ≥ 3.3 mmol/L upon initializing RRT as an independent outcome predictor.This data-driven approach can be useful for prognostication and lead to a better understanding of therapeutic strategies in heterogeneous clinical syndromes.

Prediction of intradialytic hypotension using pre-dialysis features-a deep learning-based artificial intelligence model.

BACKGROUND: Intradialytic hypotension (IDH) is a serious complication of hemodialysis (HD) that is associated with increased risks of cardiovascular morbidity and mortality. However, its accurate prediction remains a clinical challenge. The aim of this study was to develop a deep learning-based artificial intelligence (AI) model to predict IDH using pre-dialysis features. METHODS: Data from 2007 patients with 943 220 HD sessions at seven university hospitals were used. The performance of the deep learning model was compared with three machine learning models (logistic regression, random forest and XGBoost). RESULTS: IDH occurred in 5.39% of all studied HD sessions. A lower pre-dialysis blood pressure (BP), and a higher ultrafiltration (UF) target rate and interdialytic weight gain in IDH sessions compared with non-IDH sessions, and the occurrence of IDH in previous sessions was more frequent among IDH sessions compared with non-IDH sessions. Matthews correlation coefficient and macro-averaged F1 score were used to evaluate both positive and negative prediction performances. Both values were similar in logistic regression, random forest, XGBoost and deep learning models, developed with data from a single session. When combining data from the previous three sessions, the prediction performance of the deep learning model improved and became superior to that of other models. The common top-ranked features for IDH prediction were mean systolic BP (SBP) during the previous session, UF target rate, pre-dialysis SBP, and IDH experience during the previous session. CONCLUSIONS: Our AI model predicts IDH accurately, suggesting it as a reliable tool for HD treatment.

Factors associated with poor sleep quality in patients with pre-dialysis chronic kidney disease: A systematic review.

AIMS: To determine factors associated with poor sleep quality among patients with pre-dialysis chronic kidney disease. DESIGN: This is a systematic review study guided by Preferred Reporting Items for Systematic Reviews and Meta-Analyses statements and checklist. DATA SOURCES: Empirical evidence was sought in major electronic databases, including Embase, MEDLINE, CINAHL and Airiti library from March to September 2022. REVIEW METHODS: Studies investigating factors associated with poor sleep quality among adult patients with chronic kidney disease were included. Study participants who received renal replacement therapy and had sleep disorders and serious illnesses such as cancer were excluded. Of the 526 studies that resulted from the search after removing duplicate articles, 20 studies were assessed for quality by using Joanna Briggs Institute and Newcastle-Ottawa Scale by two doctorial prepared nursing scientists. RESULTS: A total of 20 studies were included in this review. The prevalence of poor sleep quality in these studies ranged from 11% to 97.5%. Demographics (older age and female), physiological conditions (higher body mass index, higher hip circumferences, higher systolic blood pressure, poor cardiovascular function, dyspnoea, pain, cramps, itchiness or moderate to extreme pruritus, lower fasting plasma glucose, electrolyte imbalance, higher total cholesterol and gastrointestinal symptoms), depression, smoking, arousal-related and cognitive arousal behaviours were associated with poor sleep quality. CONCLUSION: Poor sleep quality was prevalent and influenced kidney function, increased mortality as well as decreased quality of life in patients with pre-dialysis chronic kidney disease. This review synthesizes factors associated with poor sleep quality. Managing these factors can mitigate and prevent poor sleep quality. IMPACT: Healthcare providers, especially nurses, can assess the risk factors of poor sleep quality and reinforce patients' self-management. Future research should elucidate the assessment and management of risk factors and transfer these into widespread use in the routine care of patients with chronic kidney disease.

Pre-dialysis levels of inflammation and endotoxin in people receiving hemodialysis are not associated with blood pressure variability.

There are multiple risk factors for inflammation in dialysis. One potential cause is the presence of circulating levels of Gram-negative bacteria-derived endotoxin which is a strong inducer of inflammation. Gut-associated endotoxin may enter the circulation via a defective blood-gut barrier during episodes of hypotension or reduced perfusion. MATERIALS AND METHODS: In this study, 165 patients receiving outpatient-based hemodialysis in a facility (FHD) or at home (HHD), were studied. Levels of inflammation were quantified by developing an inflammatory score derived from the measurement of pro-inflammatory cytokines, high-sensitivity C-reactive protein (hsCRP), tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6). Intradialytic blood pressure (BP) variability and hypotension events were recorded. This included the final session of dialysis, at the commencement of which the blood samples were drawn, as well as the five preceding sessions. RESULTS: The median inflammatory score was 2 (range 0 - 3), and 30% of patients had an inflammatory score of three suggesting significant levels of inflammation. Only 8.5% had an inflammatory score of 0. Endotoxin was measured in all participants and was only positive in N = 3. The mean systolic blood pressure (SBP) was 134 ± 20 mmHg and the BP variability was 11.7 ± 3.5. In a multivariable ordinal regression model, a higher inflammatory score was significantly associated with younger age (OR 0.95, 95% CI 0.95 - 0.99, p = 0.03), higher ultrafiltration volume (OR 1.62, CI 1.04 - 2.54, p = 0.03) and lower body mass index (OR 0.9, CI 0.86 - 0.96, p = 0.01). There was no association between inflammatory score and dialysis modality, access type, kidney replacement therapy (KRT), BP variability, or endotoxin. Endotoxin was detected in only 3 of 165 patients and was not associated with inflammation. CONCLUSION: Pre-dialysis levels of inflammation are prevalent in the hemodialysis population after the long break but are not related to intradialytic BP variability or hypotension in the preceding 2 weeks. However, endotoxemia is uncommon and unlikely to be a significant driver of inflammation.

Prevalence and related factors of poor sleep quality in patients with pre-dialysis chronic kidney disease.

BACKGROUND: Sleep disturbances in patients with chronic kidney disease (CKD) are related to decreased quality of life and increased health-related risks. There is insufficient data about actual prevalence and related factors of poor sleepers in this group. In this study, we aimed to investigate prevalence and related risk factors of self-reported poor sleep quality in patients with pre-dialysis CKD. METHODS: In this cross-sectional study, 259 pre-dialysis CKD patients (median age 56 years; range, 19-85) were included. Demographical, clinical and laboratory correlates were recorded. Body mass index (BMI) was calculated. Estimated glomerular filtration rate (eGFR) was calculated by the Modification of Diet in Renal Disease (MDRD) formula. Sleep quality was assessed by Pittsburgh Sleep Quality Index (PSQI), a self-rated questionnaire. Depression was evaluated using the Beck Depression Inventory (BDI). RESULTS: Median eGFR was 27.6 ml/min/1.73 m2 (range, 9-56). Of the 259 patients, 110 (42.5%) were poor sleepers with global PSQI score >5. The univariate correlation analysis revealed that global PSQI score was positively correlated with age, BMI, waist circumferences (WC), hip circumferences (HC), serum phosphorus and triglyceride levels, systolic blood pressure (BP), pulse pressure and BDI score, and negatively correlated with male gender and hemoglobin level. Logistic regression analysis, showed that HC, systolic BP, and BDI scores were independently associated with poor sleep quality (p = 0.001, p = 0.020 and p < 0.001, respectively). CONCLUSION: Prevalence of poor sleep quality in our pre-dialysis CKD patients was 42.5%. Systolic BP, depression and HC, all of these are potentially correctable factors, were associated with poor sleep quality independently.

The impact of chronic pre-dialysis hyponatremia on clinical outcomes in maintenance hemodialysis patients.

OBJECTIVE: Chronic pre-dialysis hyponatremia is not rare in maintenance hemodialysis (MHD) patients. However, the association between chronic pre-dialysis hyponatremia and mortality is uncertain due to multiple potential confounders such as hyperglycemia, fluid overload, and malnutrition. This study aimed to more comprehensively evaluate the association between chronic pre-dialysis hyponatremia and clinical outcomes in MHD patients. METHODS: We analyzed the data of 194 MHD patients with regular real-time measurements of pre-dialysis serum sodium from July 2015 to March 2021. Hyponatremia was defined as SNa ≤ 135 mmol/L and normonatremia as SNa > 135 mmol/L and < 145 mmol/L. We evaluated the association of baseline pre-dialysis serum sodium (SNa) and time-averaged SNa (TASNa) levels with all-cause mortality or new major adverse cardiovascular events (MACE) in MHD patients. Furthermore, the SNa levels were glucose, serum albumin, and fluid overload adjusted. The associations between SNa levels and all-cause mortality or new MACE were analyzed using time-varying Cox regression models. RESULTS: Among the total of 194 patients, 24 patients died and 45 new MACE occurred during a mean 35.2-month follow-up period. The baseline pre-dialysis SNa level was 137.1 ± 2.8 mmol/L (127-144 mmol/L). Kaplan-Meier survival analysis showed that there were no significant differences in all-cause mortality or new MACE between hyponatremia and normonatremia groups according to baseline pre-dialysis SNa or glucose-corrected SNa (gcSNa). The mean values of both TASNa and time-averaged glucose-corrected SNa (TAgcSNa) were 136.9 ± 2.4 mmol/L and 138.3 ± 2.0 mmol/L, respectively. Kaplan-Meier survival analysis showed that patients with pre-dialysis hyponatremia had higher all-cause mortality or new MACE compared with normonatremia patients whether grouped on TASNa or TAgcSNa. Cox models showed an increased risk of all-cause mortality and new MACE in MHD patients with pre-dialysis hyponatremia based on TASNa or TAgcSNa. Even after full adjustment including time-dependent age and dialysis vintage, gender, diabetes, time-averaged weight gain (TAWG), and serum albumin, patients with pre-dialysis hyponatremia based on TASNa (HR 2.89; 95% CI 1.18-7.04; model 3) or TAgcSNa (HR 5.03; 95% CI 1.87-13.57; model 3) had approximately twofold or fourfold greater risk of all-cause mortality, respectively, compared with those with normonatremia. The risk of new MACE was also significantly elevated in patients with pre-dialysis hyponatremia based on TASNa (HR 3.86; 95% CI 2.13-7.01; model 1) or TAgcSNa (HR 2.43; 95% CI 1.14-5.15; model 1). After adjustment for time-dependent age and dialysis vintage, gender, diabetes, TAWG, and serum albumin, patients with pre-dialysis hyponatremia based on TASNa (HR 2.33; 95% CI 1.16-4.68; model 3) had a higher risk of new MACE compared with those with normonatremia. CONCLUSIONS: Pre-dialysis time-averaged hyponatremia is independently associated with increased risks of all-cause mortality or new MACE in MHD patients. The baseline SNa level is not a predictor of clinical outcomes due to its variation over time. Hyperglycemia, fluid overload, and malnutrition do not have a significant impact on the risk association between chronic hyponatremia and all-cause mortality or new MACE in MHD patients.

Evaluation of iron status in anemic pre-dialysis chronic kidney disease patients.

Background: Data on iron status are generally less readily available in pre-dialysis chronic kidney disease (CKD) patients than in the hemodialysis population. In Nigeria, little is known about iron indices in patients with CKD. Aims: The aim of this study was to evaluate the iron status among anemic pre-dialysis patients with CKD. Patients and Methods: Using a cross-sectional study design, we evaluated serum ferritin and transferrin saturation (TSAT) among 63 pre-dialysis CKD patients with anemia attending our outpatient nephrology clinic. CKD was defined as a glomerular filtration rate less than 60 ml/min/1.73 m2 for 3 months or more, while anemia was defined as a hemoglobin concentration (Hb) less than 11 g/dl. Results: The mean age of the study participants was 52.5 ± 12.7 years and 33 (52.4%) of the patients were females. The most common causes of CKD were hypertension (44.4%) and diabetic nephropathy (30.6%). The mean Hb, mean serum ferritin, and mean TSAT were 9.2 ± 1.1 g/dl, 106.6 ± 72.7 ng/ml, and 24.3% ± 7.9%, respectively. There was no significant difference in median ferritin (91[interquartile range: 54-133] ng/ml versus 106 [interquartile range: 45-151; P=0.75) and mean TSAT (24.9 ± 7.2 % versus 23.8 ± 7.7 %; P=0.54) between male and female study participants; Half (50.8%) of the study participants had absolute iron deficiency (serum ferritin <100 ng/ml) and 6.3% had functional iron deficiency (ferritin >100 ng/ml and TSAT <20%). Conclusion: Iron deficiency is common among anemic adult Nigerian pre-dialysis CKD patients. Results of iron studies should guide therapy when correcting anemia in these patients.

Pre-dialysis diastolic blood pressure and intradialytic hypotension in patients undergoing maintenance haemodialysis.

BACKGROUND: Intradialytic hypotension is a clinically relevant complication in haemodialysis patients. Pre-dialysis diastolic blood pressure is routinely measured. However, the association between pre-dialysis diastolic blood pressure and intradialytic hypotension is not well understood. METHODS: Patient-level (N = 545) and haemodialysis session-level (N = 3261) data were collected; the exposure variable was pre-dialysis diastolic blood pressure. The primary outcome of interest was the development of intradialytic hypotension, defined as any nadir < 100 mmHg if the pre-dialysis systolic blood pressure was ≥ 160 mmHg, or any nadir < 90 mmHg if the pre-dialysis systolic blood pressure was < 160 mmHg. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using mixed-effects logistic regression for the association between pre-dialysis diastolic blood pressure and intradialytic hypotension, after adjusting for potential confounders. RESULTS: Intradialytic hypotension occurred in 14.4% of the sessions. All sessions were divided into five categories according to pre-dialysis diastolic blood pressure. The adjusted ORs for intradialytic hypotension were 2.72 (95% CI 1.64-4.51), 1.07 (95% CI 0.68-1.66), 1.68 (95% CI 1.08-2.62), and 1.81 (95% CI 1.05-3.14) in sessions with pre-dialysis diastolic blood pressure of < 60 mmHg, ≥ 60 to < 70 mmHg, ≥ 80 to < 90 mmHg, and ≥ 90 mmHg, respectively, compared with the reference pre-dialysis diastolic blood pressure of ≥ 70 to < 80 mmHg. Cubic spline analyses revealed a reverse J-shaped association between pre-dialysis diastolic blood pressure and intradialytic hypotension. CONCLUSIONS: Low and high pre-dialysis diastolic blood pressure levels were associated with intradialytic hypotension. This may help identify patients at a high risk of developing intradialytic hypotension.

Warfarin Use, Stroke, and Bleeding Risk among Pre-Existing Atrial Fibrillation US Veterans Transitioning to Dialysis.

INTRODUCTION: Anticoagulation is commonly used for stroke prevention among patients with atrial fibrillation (AF); however, end-stage renal disease (ESRD) patients on hemodialysis are at higher risk of bleeding and stroke, even without anticoagulation. It is unclear if patients should be continued on anticoagulation at the time of transition to ESRD. In this study, we validated risk scores for stroke and bleeding in this population and assessed risk of stroke and bleeding among warfarin users compared to nonusers. METHODS: We utilized a cohort of 28,620 pre-dialysis US veterans transitioning to hemodialysis between October 2007 and March 2015. Incident rates for the risks of stroke and bleeding were ascertained based upon CHA2DS2-VASc or HAS-BLED scores, respectively. A propensity score-based competing risk analysis was used to assess risk of stroke and bleeding. FINDINGS: The mean age of our cohort was 77 ± 9 years, and the median CHA2DS2-VASc and HAS-BLED scores were 7 (5, 8) and 3 (3, 4), respectively. Increasing CHA2DS2-VASc and HAS-BLED scores were predictive of increasing stroke and bleeding rates, respectively. However, warfarin use did not appear to affect the risk of stroke and bleeding (p-interaction = 0.84 for stroke and 0.24 for bleeding). Warfarin use was associated with a higher risk of stroke (adjusted SHR 1.44, 95% CI: 1.23-1.69) and a higher risk of bleeding (adjusted SHR 1.38, 95% CI: 1.25-1.52) when accounting for the competing risk of death. DISCUSSION: There was no difference in incidence rates of stroke or bleeding among warfarin users versus nonusers. Warfarin was associated with a higher risk of stroke and bleeding after considering mortality risk.

Effect of vitamin D sterols on bone histology in pre-dialysis patients: A prospective controlled study.

BACKGROUND: Abnormalities related to mineral and bone metabolism are a common finding in chronic kidney disease (CKD). Vitamin D compounds are often prescribed to CKD patients with the purpose to control secondary hyperparathyroidism and reduce the risk of high-turnover bone disease. However, data on the effect of vitamin D sterols on bone histology in non-dialysis CKD is limited. MATERIALS AND METHODS: A prospective controlled study was conducted on a cohort of 56 patients with CKD stages 3 and 4. 19 patients on calcitriol and 12 patients on cholecalciferol were compared to a group of 25 age- and sex-matched controls. Participants underwent a tetracycline double-labelled transiliac bone biopsy before starting therapy and again 12 months later. Changes from baseline in circulating biomarkers and bone histomorphometric parameters were analyzed. RESULTS: Low-turnover bone disease was the most common pattern of renal osteodystrophy on the initial biopsy. There was no difference in biochemical or histomorphometric values between the three study groups at baseline. Serum intact parathormone (iPTH) and bone formation rate decreased significantly in calcitriol-treated patients, with prevalence of low-turnover bone disease doubling from baseline. In contrast, no significant changes were noted in cholecalciferol-treated and control subjects. CONCLUSION: Calcitriol was effective in preventing secondary hyperparathyroidism and high-turnover bone disease. However, it was associated with an increased risk of developing or aggravating low-turnover bone disease. In the absence of a bone biopsy, calcitriol use in pre-dialysis CKD should be reserved for patients with a progressive rise in iPTH levels, in whom high-turnover bone disease is suspected.

Headache changes after kidney transplant.

Headache is considered as a possible complication of dialytic treatment in chronic kidney disease (CKD). The aim of this study was to evaluate possible change in headache characteristics after kidney transplantation in patients with CKD. During a 1-year period, we enrolled 110 subjects submitted to a kidney transplant in the previous 5 years. Headache characteristics before and after the transplant were investigated by a specific questionnaire. Possible effects of pharmacological therapies were also evaluated. 65.5% of patients complained of headache before the transplant (38.2% migraine and 14.5% dialysis headache). After transplant, 53.6% of patients reported changes in headache characteristics. In particular, 27.3% of the patients had a complete resolution, 19.1% presented a headache improvement and 7.2% showed a worsening. In both migraine and dialysis headache subgroups, steroids, beta-blockers and calcium channel blockers were associated with a significant improvement of headache. Kidney transplantation seems to impact significantly headache frequency and severity in patients with CKD. A careful evaluation and use of targeted treatments could improve both patients' compliance to therapies and quality of life.

A randomized trial of albumin infusion to prevent intradialytic hypotension in hospitalized hypoalbuminemic patients.

BACKGROUND: Intradialytic hypotension (IDH) is a frequent complication of intermittent hemodialysis (IHD), occurring from 15 to 50% of ambulatory sessions, and is more frequent among hospitalized patients with hypoalbuminemia. IDH limits adequate fluid removal and increases the risk for vascular access thrombosis, early hemodialysis (HD) termination, and mortality. Albumin infusion before and during therapy has been used for treating IDH with the varying results. We evaluated the efficacy of albumin infusion in preventing IDH during IHD in hypoalbuminemic inpatients. METHODS: A randomized, crossover trial was performed in 65 AKI or ESKD patients with hypoalbuminemia (albumin < 3 g/dl) who required HD during hospitalization. Patients were randomized to receive 100 ml of either 0.9%sodium chloride or 25% albumin intravenously at the initiation of each dialysis. These two solutions were alternated for up to six sessions. Patients' vital signs and ultrafiltration removal rate were recorded every 15 to 30 min during dialysis. IDH was assessed by different definitions reported in the literature. All symptoms associated with a noted hypotensive event as well as interventions during the dialysis were recorded. RESULTS: Sixty-five patients were submitted to 249 sessions; the mean age was 58 ([Formula: see text] 12), and 46 (70%) were male with a mean weight of 76 ([Formula: see text] 18) kg. The presence of IDH was lower during albumin sessions based on all definitions. The hypotension risk was significantly decreased based on the Kidney Disease Outcomes Quality Initiative definition; (15% with NS vs. 7% with albumin, p = 0.002). The lowest intradialytic SBP was significantly worse in patients who received 0.9% sodium chloride than albumin (NS 83 vs. albumin 90 mmHg, p = 0.035). Overall ultrafiltration rate was significantly higher in the albumin therapies [NS - 8.25 ml/kg/h (- 11.18 5.80) vs. 8.27 ml/kg/h (- 12.22 to 5.53) with albumin, p = 0.011]. CONCLUSION: In hypoalbuminemic patients who need HD, albumin administration before the dialysis results in fewer episodes of hypotension and improves fluid removal. Albumin infusion may be of benefit to improve the safety of HD and achievement of fluid balance in these high-risk patients. ClinicalTrials.gov Identifier: NCT04522635.

Risk factors for carbapenem-resistant Gram-negative bacterial infections: a systematic review.

BACKGROUND: Rapid and widespread increases in carbapenem resistance (CR) necessitate identification of risk factors to guide appropriate interventions. OBJECTIVES: We aimed to identify risk factors for CR Gram-negative infection through a systematic literature review. DATA SOURCES: We searched MEDLINE (via OvidSP and PubMed) and Embase (via OvidSP) databases and the Cochrane Central Register of Controlled Trials. STUDY ELIGIBILITY CRITERIA: Prospective or retrospective cohort and case-control studies reporting quantitative data on risk factors associated with infections due to CR Gram-negative pathogens in hospitalized patients were eligible. PARTICIPANTS: Studies included hospitalized patients with CR infection caused by Gram-negative bacterial pathogens (Enterobacterales and non-fermenters). METHODS: Searches were conducted in January 2018/December 2019 to identify studies published since 2007. Risk factor data were extracted and grouped by factor. The primary metric was proportion of studies reporting a significant association with CR infection for each factor. RESULTS: In total, 92 studies were identified. Risk factors most frequently reported as significantly associated with CR infection (>10 studies) were previous antibiotic use (91.1%; 72/79 studies); previous carbapenem use (82.6%; 57/69); previous colonization (72.7%; 8/11); mechanical ventilation (66.7%; 36/54); previous intensive care unit stay (64.4%; 38/59); dialysis (61.1%; 11/18); catheter (58.0%; 40/69); length of stay in hospital (54.5%; 30/55); comorbidities (52.7%; 39/74); APACHE II (51.7%; 15/29); and intubation (51.4%; 18/35). Risk factors were mostly consistent across different species and sites of infection. CONCLUSIONS: Several variables, particularly previous antibiotic use, are strong risk factors for CR infection. Interventions to mitigate against CR infection should target these factors.

Trends in Cardiovascular Mortality Among a Cohort of Children and Young Adults Starting Dialysis in 1995 to 2015.

Importance: Survival of patients receiving dialysis has improved during the last 2 decades. However, few studies have examined temporal trends in the attributed causes of death (especially cardiovascular-related) in young populations. Objective: To determine temporal trends and risk of cause-specific mortality (ie, cardiovascular and infectious) for children and young adults receiving dialysis. Design, Setting, and Participants: This retrospective cohort study examined the records of children and young adults (aged <30 years) starting dialysis between 1995 and 2015 according to the United States Renal Data System database. Analyses were performed between June 2019 and June 2020. Fine-Gray models were used to examine trends in risk of different cardiovascular-related deaths. Models were adjusted for age, sex, race, neighborhood income, cause of end-stage kidney disease, insurance type, and comorbidities. Analyses were performed separately for children (ie, age <18 years) and young adults (between ages 18 and 30 years). Follow-up was censored at death or administratively, and transplantation was treated as a competing event. Exposures: Calendar year. Main Outcomes and Measures: Cardiovascular cause-specific mortality. Results: A total of 80 189 individuals (median [interquartile range] age, 24 [19-28] years; 36 259 [45.2%] female, 29 508 [36.8%] Black, and 15 516 [19.3%] Hispanic white) started dialysis and 16 179 experienced death during a median (interquartile range) of 14.3 (14.0-14.7) years of follow-up. Overall, 40.2% of deaths were from cardiovascular-related causes (6505 of 16 179 patients). In adjusted analysis, risk of cardiovascular-related death was stable initially but became statistically significantly lower after 2006 (vs 1995) in those starting dialysis as either children (subhazard ratio [SHR], 0.74; 95% CI, 0.55-1.00) or adults (SHR, 0.90; 95% CI, 0.83-0.98). Risk of sudden cardiac death improved steadily for all age groups, but to a greater degree in children (SHR, 0.31; 95% CI, 0.20-0.47) vs young adults (SHR, 0.64; 95% CI, 0.56-0.73) comparing 2015 vs 1995. Risk of stroke became statistically significantly lower around 2010 (vs 1995) for children (SHR, 0.40; 95% CI, 0.18-0.88) and young adults (SHR, 0.76; 95% CI, 0.59-0.99). Conclusions and Relevance: In this study, the risk of cardiovascular-related death declined for children and young adults starting dialysis during the last 2 decades, but trends differed depending on age at dialysis initiation and the specific cause of death. Additional studies are needed to improve risk of cardiovascular disease in young populations.

Transmission of SARS-CoV-2 Involving Residents Receiving Dialysis in a Nursing Home - Maryland, April 2020.

SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), can spread rapidly in nursing homes once it is introduced (1,2). To prevent outbreaks, more data are needed to identify sources of introduction and means of transmission within nursing homes. Nursing home residents who receive hemodialysis (dialysis) might be at higher risk for SARS-CoV-2 infections because of their frequent exposures outside the nursing home to both community dialysis patients and staff members at dialysis centers (3). Investigation of a COVID-19 outbreak in a Maryland nursing home (facility A) identified a higher prevalence of infection among residents undergoing dialysis (47%; 15 of 32) than among those not receiving dialysis (16%; 22 of 138) (p<0.001). Among residents with COVID-19, the 30-day hospitalization rate among those receiving dialysis (53%) was higher than that among residents not receiving dialysis (18%) (p = 0.03); the proportion of dialysis patients who died was 40% compared with those who did not receive dialysis (27%) (p = 0.42).Careful consideration of infection control practices throughout the dialysis process (e.g., transportation, time spent in waiting areas, spacing of machines, and cohorting), clear communication between nursing homes and dialysis centers, and coordination of testing practices between these sites are critical to preventing COVID-19 outbreaks in this medically vulnerable population.