Poor neutralization and rapid decay of antibodies to SARS-CoV-2 variants in vaccinated dialysis patients.

Patients on dialysis are at risk of severe course of SARS-CoV-2 infection. Understanding the neutralizing activity and coverage of SARS-CoV-2 variants of vaccine-elicited antibodies is required to guide prophylactic and therapeutic COVID-19 interventions in this frail population. By analyzing plasma samples from 130 hemodialysis and 13 peritoneal dialysis patients after two doses of BNT162b2 or mRNA-1273 vaccines, we found that 35% of the patients had low-level or undetectable IgG antibodies to SARS-CoV-2 Spike (S). Neutralizing antibodies against the vaccine-matched SARS-CoV-2 and Delta variant were low or undetectable in 49% and 77% of patients, respectively, and were further reduced against other emerging variants. The fraction of non-responding patients was higher in SARS-CoV-2-naïve hemodialysis patients immunized with BNT162b2 (66%) than those immunized with mRNA-1273 (23%). The reduced neutralizing activity correlated with low antibody avidity. Patients followed up to 7 months after vaccination showed a rapid decay of the antibody response with an average 21- and 10-fold reduction of neutralizing antibodies to vaccine-matched SARS-CoV-2 and Delta variant, which increased the fraction of non-responders to 84% and 90%, respectively. These data indicate that dialysis patients should be prioritized for additional vaccination boosts. Nevertheless, their antibody response to SARS-CoV-2 must be continuously monitored to adopt the best prophylactic and therapeutic strategy.

Morbidity and mortality on chronic haemodialysis: a 10-year Swiss single centre analysis.

BACKGROUND: Patient survival on chronic haemodialysis varies considerably among different countries and healthcare systems. To date, the survival of Swiss dialysis patients has not been analysed separately. METHODS: We consecutively enrolled 266 patients entering the chronic haemodialysis program of the University Hospital Basel between 01.01.1995 and 30.06.2006 into a cohort study. Patient survival on chronic haemodialysis was the primary endpoint. Pre-specified sub-group analyses were performed for female and diabetic patients. RESULTS: Patient age ranged from 15 to 90 years. Seventy-two percent suffered either from coronary artery, peripheral artery or cerebrovascular disease and 34% from diabetes. Sixty-nine (26%) patients underwent kidney transplantation. Transplanted patients were significantly younger (p <0.01) and less likely to suffer from diabetes (p <0.01) and atherosclerotic diseases (coronary, peripheral, cerebrovascular p for all ≤0.01). Median survival was 4.25 years (95%CI 3.66-5.50), with one, three and five year survival rates reaching 88%, 68% and 46%. Survival rates were equal in men and women (p = 0.34), among diabetic and non-diabetic patients (p = 0.41) and among men and women stratified for the presence of diabetes (p = 0.13). Overall, 34% (91/266) patients died during the observational period. Thirty three percent of all deaths were caused by cardiac events, followed by malignant diseases (8%) and infections (7%). In 9% (23/266) dialysis was withdrawn and withdrawal of dialysis contributed to death in 25% (23/91). CONCLUSION: Survival on chronic haemodialysis treatment in Switzerland compares favourably to international reference values. Dialysis withdrawal and the frequency of kidney transplantation impact long term patient outcome and should be adjusted for when comparing mortality analysis.

[Medication non adherence - predictive factors and diagnostics]. / Medikamentöse Nicht-Adhärenz - Prädiktive Faktoren und Diagnostik.

There are many complex reasons for medication non adherence and a gold standard to assess medication non adherence does not exist. We present factors associated with medication non adherence using the five adherence dimensions suggested by the World Health Organization as well as the subjective appraisal regarding medication intake of the patient as suggested by the National Institute of Health and Clinical Excellence in the UK. Based on current research based knowledge, we suggest a two step adherence assessment for the clinical setting: 1) a routine assessment (screening) using patient self-report complemented by non adherence evidence from other methods; 2) in-depth adherence assessment for patients with positive non adherence evidence via interview. The adherence assessment turns then into adherence support. Adherence is the result of a skilled collaborative partnership between patients and health professionals. In complex cases adherence has to be regarded as an aim to be achieved in several stages.

Incidence and prediction of early antibody-mediated rejection due to non-human leukocyte antigen-antibodies.

BACKGROUND: Antibody-mediated rejection (AMR) is responsible for a large proportion of early allograft losses. While preformed donor-specific human leukocyte antigen (HLA)-antibodies (HLA-DSA) are accountable for the majority of these episodes, non-HLA-DSA are also involved. However, data on the incidence of early AMR due to non-HLA-DSA are currently lacking. METHODS: This study evaluated (i) the incidence of early AMR due to non-HLA-DSA -- defined by exclusion of circulating HLA-DSA detected by flow beads -- and (ii) the association with donor-specific major histocompatibility complex class I chain-related gene (MICA)-antibodies (MICA-DSA) and angiotensin-receptor antibodies. A retrospective cohort (n=279) risk stratified by complement-dependent cytotoxicity crossmatches (CDC-XM era) and a prospective cohort (n=154) risk stratified by virtual crossmatching using flow beads (virtual-XM era) were investigated. RESULTS: In the CDC-XM era 25/279 patients (9%) developed early AMR, but only 3/154 patients (2%) in the virtual-XM era (P=0.004). The incidence of early AMR due to HLA-DSA was significantly higher in the CDC-XM era than in virtual-XM era (18/279 patients [6.5%] vs. 0/154 patients [0%]; P=0.0005). However, the incidence of early AMR presumably due to non-HLA-DSA remained unchanged in these two cohorts (7/279 patients [2.5%] vs. 3/154 patients [2%]; P=1.0) consistent with a persisting gap in the ability to identify preformed DSA. Overall, 10/433 patients (2.3%) experienced early AMR presumably due to non-HLA-DSA. None of these 10 patients had angiotensin-receptor antibodies, at most 3/10 patients had MICA-DSA, while the antibodies remained unexplained in 7/10 cases. CONCLUSION: Early AMR due to non-HLA-DSA is a rare event, which is still difficult to predict by currently available assays.

Contribution of early failure to outcome on peritoneal dialysis.

BACKGROUND: The technique failure rate on peritoneal dialysis (PD) remains high despite technical progress. There are no data concerning the contribution of early failure to outcome on PD. AIM: To analyze the importance of early treatment failure in PD and to compare early with late failures with respect to reasons and predictors of risk for failure. METHODS: We performed a retrospective study of all patients admitted for PD from October 1983 to June 2005. The end point was PD failure-free survival. Differences between reasons for failure with respect to early (within 6 months) and late failure were analyzed. Multivariate associations of baseline covariates with early and late failure were investigated. RESULTS: We included 279 patients. 153 (55%) patients experienced PD failure: 97 (63%) of them had technique failure; 56 (37%) patients died due to non-PD-related causes. 29% (n = 44) of all PD failures and 40% (n = 39) of all technique failures occurred within 6 months. Catheter and psychosocial problems contributed more often to early than to late failure, whereas infections, leakages, and hernias contributed equally to early and late failure. Death was the predominant reason for late failure. Female sex was a risk factor for early failure and older age a risk factor for late failure. Higher cholesterol levels were associated with a decreased risk for both early and late failure. CONCLUSION: The contribution of early failure to outcome on PD is important, as one third of all PD failures and 40% of all technique failures may occur within the first 6 months, as shown in our study. Due to the retrospective nature and the single-center character, the results cannot be generalized. However, it is important to enhance recognition of patients at high risk for early PD failure prior to initiation of PD, in order to avoid unnecessary surgical interventions and medical complications, and for rational resource allocation.

Pseudotumor of gout in the patella of a kidney transplant recipient.

BACKGROUND: A 33-year-old renal transplant recipient presented with painless swelling of the right knee. Physical examination revealed an impressive knee joint effusion with no signs of inflammation. The patient did not remember a recent trauma, but he mentioned a strain 3 years earlier; radiographic findings had been normal at that time. The patient had suffered from end-stage renal disease due to chronic glomerulonephritis and had previously undergone two transplantations. At presentation, his kidney function was stable under treatment with ciclosporin, azathioprine and steroids. INVESTIGATIONS: Conventional radiography revealed a tumor at the superolateral pole of the right patella. Extensive soft tissue invasion and bone destruction was seen on MRI. A knee arthroscopy with biopsy, performed to aid diagnosis, showed extensive chondrocalcinosis macroscopically; histologically, gouty tophi were found. DIAGNOSIS: Pseudotumor of gout in the patella. MANAGEMENT: Uric-acid-lowering therapy with benzbromarone was started immediately after diagnosis. A local arthroscopic debridement of the right knee joint was performed 4 months later, and the patient remained asymptomatic for the next 3 years.

Prevalence and consequences of nonadherence to hemodialysis regimens.

Adherence to fluid restrictions and dietary and medication guidelines as well as attendance at prescribed hemodialysis sessions of a hemodialysis regimen are essential for adequate management of end-stage renal disease. A literature review was conducted to determine the prevalence and consequences of nonadherence to the different aspects of a hemodialysis regimen and the methodological obstacles in research on nonadherence. Nonadherence to the prescribed regimen is a common problem in hemodialysis and is associated with increased morbidity and mortality. Research on nonadherence is associated with 2 major obstacles: inconsistencies in definitions and invalid measurement methods. Further research is needed to validate measurement methods and to establish clinically relevant operational definitions of nonadherence.

Measurement of PTH fragments for assessment of renal bone disease in hemodialysis patients.

BACKGROUND: Renal bone pathology involves a spectrum from 'high-turnover' to 'low-turnover bone disease' (adynamic bone disease, classical osteomalacia). The diagnosis of the latter usually requires bone biopsy. Inhibitory parathyroid hormone (PTH) fragments may be useful for its noninvasive diagnosis. METHODS: A cross-sectional study was performed in 54 patients on chronic hemodialysis which involved measurements of intact PTH (iPTH; Nichols assay), total PTH (tPTH; Scantibodies assay), and the cyclase-activating PTH fragment (CAP). The level of cyclase-inactive PTH fragment (CIP) was calculated. At the same time, serum calcium, phosphorus, and alkaline phosphatase levels as well as the current therapy for secondary hyperparathyroidism were recorded. In selected patients, bone radiographs were evaluated for osteitis fibrosa. RESULTS: A high correlation (r = 0.94) was found between iPTH and tPTH, with the tPTH levels being lower by 30-40%. A similar association was also found for CAP (r = 0.988) and for CIP (r = 0.93). 3 out of the 54 patients had a CAP/CIP ratio of < or =1 which has been associated with adynamic bone disease. A higher CIP ratio was significantly associated with the use of aluminum-hydroxide- and calcium-containing phosphate binders. CONCLUSIONS: iPTH and tPTH assays are highly correlated. In a general hemodialysis patient population, low-turnover bone disease appears to be rare, when the CAP/CIP ratio is used as a marker. A high CIP value was associated with therapy using aluminum hydroxide, a drug known to carry a risk of adynamic bone disease.

Interpretation of erythropoietin levels in patients with various degrees of renal insufficiency and anemia.

BACKGROUND: Chronic renal failure leads to hyporegenerative anemia due to erythropoietin deficiency. The creatinine clearance and hemoglobin levels, at which anemia treatment with recombinant erythropoietin should be started, are unclear. Interpretation of serum erythropoietin levels in the context of renal insufficiency remains controversial and was addressed in this study. METHODS: Three hundred and ninety-five patients were randomly chosen out of over 5000 consecutive patients investigated by coronary angiography at a single center between 1997 and 2001. Laboratory values and clinical information were prospectively collected in a central registry. Serum samples were frozen before angiography and now used to measure serum erythropoietin levels and evaluate the relationship between erythropoietin and hemoglobin levels in the context of various degrees of renal insufficiency. RESULTS: The patients with the lowest renal function (creatinine clearance <20 mL/min) had significantly lower hemoglobin levels than the group with normal renal function. However, erythropoietin levels were identical indicating a lower set point for erythropoietin regulation. Above a creatinine clearance of 40 mL/min a significant inverse correlation between erythropoietin and hemoglobin levels was observed and described with the formula erythropoietin [U/L]= 2.5 x (140 - hemoglobin [g/L]) or alternatively Deltaerythropoietin (U/L) =-2.5 xDeltahemoglobin (g/L). Below 40 mL/min no significant correlation was found. CONCLUSION: A cut-off level for an altered set point of erythropoietin regulation was determined at 40 mL/min creatinine clearance. Above this cut-off hemoglobin negatively regulates erythropoietin. Below the cut-off erythropoietin levels remain stable. Pathophysiologic concepts for this finding and clinical implications in patients with moderate renal failure are discussed.

Characteristics of hypotension-prone haemodialysis patients: is there a critical relative blood volume?

BACKGROUND: Intradialytic morbid events (IME, mostly hypotension) mainly due to ultrafiltration-induced hypovolaemia still are the most frequent complication during haemodialysis (HD). This study was performed to test the hypothesis that there is an individual critical relative blood volume (RBV(crit)) in IME-prone HD patients. METHODS: In this prospective international multicentre study, 60 IME-prone patients from nine dialysis centres were observed during up to 21 standard HD sessions without trial-specific intervention. The RBV was monitored continuously by an ultrasonic method (BVM; blood volume monitor). Also, the ultrafiltration rate was registered continuously. Blood pressure was measured at regular intervals, and more frequently during IME. All IME and specific therapeutic interventions were noted. RESULTS: In total, 537 IME, some with more than one symptom, were documented during 585 HD sessions. The occurrence of IME increased up to 10-fold from the start to the end of the HD session. RBV(crit) showed a wide inter-individual range, varying from 71 to 98%. However, the intra-individual RBV limit was relatively stable, with an SD of <5% in three-quarters of the patients. In patients with congestive heart failure, cardiac arrhythmia, advanced age, low ultrafiltration volume and low diastolic blood pressure, higher values of RBV(crit) were observed. While all correlations between RBV(crit) and patient characteristics alone were found to be of weak or medium strength, the combination of diastolic blood pressure, ultrafiltration volume and age resulted in a strong correlation with RBV(crit): the linear equation with these parameters allows an estimation of RBV(crit) in patients not yet monitored with a BVM. CONCLUSIONS: An individual RBV limit exists for nearly all patients. In most IME-prone patients, these RBV values were stable with only narrow variability, thus making it a useful indicator to mark the individual window of haemodynamic instabilities.