Search

Objective: The purpose of this study was to describe the clinical features of AAV and identify possible risk factors for end-stage renal disease (ESRD) and mortality in AAV based on the experience of a single center in China. Methods: A prospective cohort study of AAV was conducted based on data acquired by the Chinese Rheumatism Data Center (CRDC). The cohort involved 140 patients diagnosed with AAV in the Second Affiliated Hospital of Nanchang University from January 2013 to April 2022. Clinical characteristics and prognostic data were prospectively collected. The patients were divided into an ESRD group and a non-ESRD group, a death group and a survival group, Then, univariate and multivariate COX regression models were used to determine the risk factors associated with ESRD and mortality by AAV. Results: Multivariate Cox regression results showed that high initial serum creatinine (hazard ratio (HR) = 1.001, 95% confidence interval (CI): 1.000–1.002, P = 0.024), high initial Birmingham vasculitis activity score (BVAS) (HR = 1.081, 95% CI: 1.027–1.138, P = 0.003), and the need for dialysis treatment (HR = 4.918, 95% CI: 1.727–14.000, P = 0.003) were independent risk factors for the progression of ESRD in AAV patients. Multivariate Cox regression results showed that alveolar hemorrhage (HR = 3.846, 95% CI: 1.235–11.973, P = 0.020), interstitial lung disease (HR = 4.818, 95% CI: 1.788–12.982, P = 0.002), and low initial estimated glomerular filtration rate (EGFR) (HR = 0.981, 95% CI: 0.968–0.995, P = 0.009) were independent risk factors for the prediction of death in AAV patients. Conclusion: These findings suggest that high initial serum creatinine, a high initial BVAS score, and the need for dialysis were independent risk factors for the progression of ESRD in AAV patients. Alveolar hemorrhage, interstitial lung disease, and low initial EGFR were independent risk factors for death. Key Points • The risk factors for ESRD in AAV determined in this study are high initial serum creatinine, a high initial BVAS score, and the need for dialysis. • The risk factors for mortality in AAV are alveolar hemorrhage, interstitial lung disease, and low initial EGFR. [ABSTRACT FROM AUTHOR]

We investigated if elevated cardiac troponin I (cTnI) serum levels before non-cardiac surgery were predictors of postoperative cardiac events in patients with end stage renal disease (ESRD) undergoing dialysis. In total, 703 consecutive patients with ESRD undergoing dialysis who underwent non-cardiac surgery were enrolled. Preoperative cTnI serum levels were measured at least once in all patients. The primary endpoint was defined as a composite of cardiac death, myocardial infarction (MI), and pulmonary edema during hospitalization or within 30 days after surgery in patients with a hospitalization longer than 30 days after surgery. Postoperative cardiac events occurred in 48 (6.8%) out of 703 patients (cardiac death 1, MI 18, and pulmonary edema 33). Diabetes mellitus (DM), previous ischemic heart disease, and congestive heart failure were more common in patients with postoperative cardiac events. Peak cTnI serum levels were higher in patients with postoperative cardiac event (180 ± 420 ng/L vs. 80 ± 190 ng/L, p = 0.008), and also elevated peak cTnI levels > 45 ng/L were more common in patients with postoperative cardiac events (66.8% vs. 30.5%, p < 0.001). Multivariate logistic regression analysis showed that DM (odds ratio [OR] 2.509, 95% confidence interval [CI] 1.178–5.345, p = 0.017) and serum peak cTnI levels ≥ 45 ng/L (OR 3.167, 95% CI 1.557–6.444, p = 0.001) were independent predictors for the primary outcome of cardiac death/MI/pulmonary edema. Moreover, cTnI levels ≥ 45 ng/L had an incremental prognostic value to the revised cardiac risk index (RCRI) (Chi-square = 23, p < 0.001), and to the combined RCRI and left ventricular ejection fraction (Chi-square = 12, p = 0.001). Elevated preoperative cTnI levels are predictors of postoperative cardiac events including cardiac death, MI, and pulmonary edema in patients with ESRD undergoing non-cardiac surgery. [ABSTRACT FROM AUTHOR]

Background: Pretherapeutic screening for dihydropyrimidine dehydrogenase (DPD) deficiency is recommended prior to the administration of fluoropyrimidine-based chemotherapy. However, the best strategy to identify DPD deficiency in End Stage Renal Disease (ESRD) patients is unknown.Methods: We assessed the characteristics of both DPD phenotypes and DPYD genotypes in 20 dialyzed patients before and after dialysis session. The extent to which the concentrations of uracil [U] and dihydrouracil [UH2] were affected by dialysis was evaluated.Results: Mean [U] was 14 ± 3.3 ng/ml before the dialysis session, and 7.9 ± 2.7 ng/ml after. Notably, mean [U] in 119 non-ESRD patients during the same timeline was 8.7 ± 3.9 ng/ml, which is similar to [U] values after dialysis session (p = 0.38). [U] values > 16 ng/ml were measured in 4 ESRD patients (20%), whereas the rate was 3.3% in the non-ESRD cohort. Whole gene sequencing did not reveal DPYD deleterious allelic variants in the 4 ESRD patients with [U] values > 16 ng/ml. The profile of [UH2] values during dialysis was similar to that of [U]: 385 ± 86 ng/ml before, and 185 ± 62 ng/ml after (mean reduction rate 42.5%). Thus, [UH2]:[U] ratio remained unaffected by dialysis, and was similar to the values in non-ESRD patients (22.4 ± 7.1).Conclusion: Phenotyping based on measuring plasma [U] before a dialysis sessions in ESRD patients is associated with an unacceptable high rate of false positives. The optimal strategy for the identification of patients with DPD deficiency in this population would be the monitor the [UH2]:[U] ratio, which remains unaffected. [ABSTRACT FROM AUTHOR]

Background: Patients with kidney failure have multifaced clinical needs. Continuous quality improvement (CQI) programs initiated by large healthcare provider networks bear the promise of improving guideline adherence and improving patient-centered outcome, including health-related quality of life (HRQOL). We aimed at evaluating the association between key performance indicators (KPI) adopted for our CQI and HRQOL in a large network of dialysis providers. Methods: We conducted a survey study in 39 centers belonging to the Portuguese Fresenius Medical Care (FME) network, in September 2017. For each participant, we retrospectively extracted clinical information during the 6-month period preceding survey administration. We used this information to calculate KPI as defined by the FME-CQI policy. Those KPI were selected in the FME-CQI policy as modifiable intermediate endpoints for which previous evidence suggested a causal relationship with patients' morbidity and mortality. HRQOL was assessed by the Kidney Disease Quality of Life Short Form 36 (KDQOL-36) questionnaire. Results: Among 4691 eligible patients who were invited to participate in the survey, 2263 (48.2%) answered the self-administered survey. Based on KPI standards, patients had 1.5 (± 1.2) off-target clinical parameters on average. KDQOL-36 score were generally higher than those observed in European reference population. We found a significant linear association between KPI parameters and HRQOL. This pattern was robust to adjustment for satisfaction scores. Conclusions: Our data demonstrated a graded, monotonic, dose–response relationship between the number of off-target KPIs and HRQOL. Such relationship was not mediated by patients' satisfaction and may be attributed to amelioration of disease-specific symptoms and functional capacity. [ABSTRACT FROM AUTHOR]

Acquired cystic kidney disease (ACKD) is a condition that occurs predominantly in patients with end-stage renal disease (ESRD). In contrast to hereditary cystic kidney disease, ACKD is characterized by the presence of multiple small cysts in bilaterally small kidneys. Limited pediatric data suggest a high incidence (21.6-45.8%) of ACKD in children on dialysis, comparable to that in adults, with an increased frequency associated with a longer duration of dialysis. Recent research has shed light on the pathogenesis of ACKD, such as activation of proto-oncogenes. Although most patients with ACKD are asymptomatic, the condition can be complicated by renal cell carcinoma. Routine surveillance should therefore be considered in at-risk populations. [ABSTRACT FROM AUTHOR]

Polycystic kidney disease (PKD) is a systemic disorder which adds majority of renal patients to end stage renal disease. Autosomal dominant polycystic kidney disease (ADPKD) is more prevalent and leading cause of dialysis and kidney transplant. Linkage analysis revealed some closely linked loci, two of which are identified as PKD1, PKD2 and an unidentified locus to ADPKD. This study was performed using PCR and automated DNA sequencing in 84 cases and 80 controls to test potential candidature of PKD2 as underlying cause of PKD by in silico and statistical analyses. Two associated symptoms, hypertension (19%) and liver cyst (31%) havemajor contribution to PKD. Gender-based analysis revealed that familial female patients (27%) and familialmale patients (33%) are more hypertensive. Liver cyst, the second major contributing symptom presented by large percentage of sporadic males (46%). Genetic screening of all 15 exons of PKD2 revealed eight pathogenic (c.854_854delG, c.915C>A, c.973C>T, c.1050_1050delC, c.1604_1604delT, c.1790T>C, c.2182_2183delAG, c.2224C>T) and eight likely pathogenic (g.11732A>G, c.646T>C, c.1354A>G, g.39212G>C, c.1789C>A, c.1849C>A, c.2164G>T, c.2494A>G)DNA sequence variants. In our study, 27.38% (23/84) cases shown pathogenic / likely pathogenic variants in PKD2 gene. Some regions of PKD2 prone for genetic variation suggested to be linked with disease pathogenesis. This noticeable hot spot regions hold higher frequency (50%) of pathogenic / likely pathogenic genetic variants constituting single nucleotide variants than large deletion and insertion that actually represents only 41.08% of coding sequence of PKD2. Statistically significant association for IVS3-22AA genotype was observed with PKD, while association of IVS4+62C>Twas found insignificant. [ABSTRACT FROM AUTHOR]

Background and Aims: The patients with end stage renal disease (ESRD) are at greater risk of acquiring chronic hepatitis B or C and subsequently development of liver disease. The aim of the study was to assess liver fibrosis by transient elastography (TE) and look for factors associated with change in liver stiffness measurement (LSM) with one session of hemodialysis (HD).Methods: Consecutive ESRD patients on maintenance hemodialysis (MHD) with suspected liver disease were enrolled. They underwent LSM by TE before and after one session of HD. Bioelectric impedance analysis was done to evaluate the volume status at the time of TE.Results: Sixty-eight patients with mean age of 40 ± 14 years were included. There was a significant reduction in LSM after HD (18.5 [95% CI 14.8-23.1] vs. 11.2 [95% CI 8.8-13.7] kPa, p < 0.001), with a mean LSM reduction of 7.2 [95% CI 5.25-9.19] kPa. On stratification in two groups by net ultrafiltration during HD (> or < 2.5 liters [L]), change in LSM was substantially higher in patients when total fluid removed was > 2.5 L (8.6 [95% CI 5.7-11.5] vs. 5.1 [95% CI 2.9-7.5], p = 0.05). In 18 patients who underwent liver biopsy, LSM after HD performed better at detecting significant fibrosis, with area under receiver operating characteristics curve 0.71 [95% CI 0.46-0.97], versus 0.64 [95% CI 0.38-0.90], respectively. An LSM value of 12.2 kPa after HD was 71% sensitive and 74% specific for detection of significant fibrosis (≥ F2), while values less than 9 kPa ruled out significant fibrosis with a sensitivity and specificity of 37 and 100%, respectively.Conclusion: LSM by TE decreases significantly after HD in patients with ESRD on long-term MHD. Hence, TE should be done after HD for accurate assessment of liver fibrosis. [ABSTRACT FROM AUTHOR]

Purpose: The pharmacokinetics (PK) of carfilzomib have been previously studied in multiple myeloma patients with varying degrees of renal impairment (normal, mild, moderate, severe, and end-stage renal disease [ESRD]) at doses of 15 and 20 mg/m2. This study evaluated carfilzomib PK at higher doses of 27 and 56 mg/m2 in normal renal function and ESRD patients.Methods: Patients received carfilzomib on two consecutive days/week for 3 weeks every 28-day cycle: 20 mg/m2 (cycle 1 day 1-2), escalated to 27 mg/m2 on cycle 1 day 8; if tolerated, 56 mg/m2 starting cycle 2 day 1. The primary objective was PK assessment with safety/tolerability and response rate as secondary and exploratory objectives, respectively.Results: 26 patients were enrolled (15 normal, 11 ESRD). There was a trend toward higher area under the concentration time curve (AUC) and maximum concentration in ESRD versus normal renal function patients; however, high interpatient PK variability was discerned. Relative to patients with normal renal function, ESRD patients showed 33% higher AUC. Overall response rate was 43% for the normal renal function and 60% for the ESRD groups. Safety findings were generally similar between the two groups and consistent with the known safety profile of carfilzomib in multiple myeloma patients.Conclusion: There were no meaningful differences in PK between patients with normal renal function and ESRD in light of carfilzomib exposure-response relationships. These results continue to support dosing recommendation that no starting dose adjustment of carfilzomib appears warranted in patients with baseline renal impairment. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the effect of a 12-week intradialytic progressive resistance training (PRT) regimen on circulating pro- and anti-inflammatory cytokines. Forty-nine patients (62.6 ± 14.2 years) were recruited from the outpatient hemodialysis unit of the St. George Public Hospital, Sydney, Australia. Patients were randomized to: PRT + usual care (n = 24) or usual care control (n = 25). The PRT group performed two sets of 10 exercises at high intensity using free-weights, 3 times per week for 12 weeks during dialysis, while the control group did not exercise. Tumor necrosis factor-alpha, interleukin-1b, interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10, and interleukin-12 were measured in serum before and after the intervention period. Muscle cross-sectional area (CSA), intramuscular lipid, intermuscular adipose tissue, and subcutaneous and total thigh fat, evaluated via computed tomography of the non-dominant mid-thigh, were also collected at both time points. All cytokines were significantly elevated in the total cohort at baseline compared with normative data. There were no cytokine changes over time or between groups (p > 0.05). In secondary analyses pooling the groups, changes in logIL-6 and IL-8 were inversely related to changes subcutaneous thigh fat (p < 0.05) while changes in logIL-6 were also inversely related to changes in thigh muscle CSA, and total thigh fat (p < 0.03). These data suggest that 12 weeks of intradialytic progressive resistance training does not improve circulating pro- and anti-inflammatory markers. Further research is required to elucidate the implications and mechanisms of the relationships between IL-6 and IL-8 and body composition in ESRD. [ABSTRACT FROM AUTHOR]

During recent years, the importance of intensified dialysis regimens has gathered increasing interest, especially after the Hemodialysis (HEMO) Study Group reported that a higher dose of thrice-weekly hemodialysis failed to improve clinical outcomes. Long nocturnal hemodialysis (three to six times per week) or short daily hemodialysis are the currently used forms of intensified dialysis. There is substantial evidence for cardiovascular and quality-of-life improvements as well as financial benefits with intensified hemodialysis. Preliminary experience with daily hemodialysis and hemodiafiltration in children has been reported. Given the continuing shortage of donor organs for kidney transplantation, the increasing incidence of end-stage renal disease (ESRD) and recognition of the deleterious effects of long-lasting ESRD, growth retardation, and poor social rehabilitation, more intensified dialysis regimens are a much-needed therapeutical option in both adults and children. [ABSTRACT FROM AUTHOR]

End stage renal disease (ESRD) can cause malfunction of multiple organs, including auditory and vestibular systems. During recent years, a significant amount of research has demonstrated the direct involvement of the otolith organs in stabilizing body and gaze which led to the development of specific functional tests. Stable gaze and body are more important in patients with ESRD, as they have an increased risk of bone fracture. The aim of this study was to investigate saccule and related neural pathways in haemodialysed patients with chronic renal failure. Twenty patients (40 ears) with ESRD were tested for vestibular evoked myogenic potentials (VEMP). Results were compared with those of 16 healthy controls (32 ears). VEMP response was significantly different between subjects and patients with ESRD. There was a significant difference between the presence and absence of VEMP waves in ESRD patient when compared with creatinine levels. [ABSTRACT FROM AUTHOR]

Purpose: Recently, several studies have shown that renal failure decreases the metabolic clearance of drugs and the transportation capability of some drug transporters. However, whether organic anion transporting polypeptide (OATP)1B activities decrease in renal failure remains unknown. In this study, we measured plasma concentrations of coproporphyrin-I (CP-I), a specific endogenous OATP1B probe, in patients with end stage renal disease before and after living kidney transplantation and evaluated the effect of renal function on OATP1B activity. Methods: This prospective study recruited 13 patients with end-stage renal disease. Plasma CP-I concentrations were measured before and 7, 14, 30 and 90 days after living kidney transplantation. Results: Plasma CP-I concentrations decreased over time after living kidney transplantation and showed significant difference on day 90 compared with before living kidney transplantation [1.12 ± 0.59 vs 0.65 ± 0.27 ng/mL, p < 0.05 (95% CI of difference − 0.927, −0.013)]. A significant negative correlation was observed between estimated glomerular filtration rate and plasma CP-I concentration (r = −0.30, p < 0.05), suggesting recovery of OATP1B activity with improvement in renal function. Conclusions: OATP1B activity may decrease in renal failure and dose adjustment of OATP1B substrates may be needed in patients with renal failure. [ABSTRACT FROM AUTHOR]

A quiz concerning the case study of a 15-year-old Saudi Arabian boy presented with painless hard subcutaneous swellings in his fingers with intact overlying skin is presented.