IgA nephropathy (IgAN) accounts for a far higher proportion of end-stage renal disease (ESRD) in Asia compared with North America. It is not known whether this is entirely because of differences in ...disease prevalence or a higher risk of disease progression. The lack of a racially diverse population cohort followed longitudinally has previously precluded the ability to address this question. To determine whether Asians in North America with IgAN are at higher risk for ESRD, we analyzed a cohort of 202 patients of self-reported Pacific Asian origin and 467 of other origin from the Toronto GN Registry followed up for a median of 46.4 months. The primary outcome of ESRD (dialysis, transplantation, or eGFR below 15) was analyzed using Cox regression analysis. Baseline eGFR was 59.6ml/min/1.73m2, and median proteinuria was 1.8g/day. ESRD occurred in 213 patients. By univariable analysis, the risk of ESRD was similar between the two groups (hazard ratio 0.98, 95% CI 0.73, 1.31); however, after adjusting for age, gender, eGFR, medication use, blood pressure, and proteinuria, the risk of ESRD was significantly higher in Pacific Asian individuals (hazard ratio 1.56, 95% CI 1.10, 2.22). This was supported by a significant 1.62ml/min/1.73m2/year faster rate of eGFR decline (95% CI –3.19, –0.5) and an increased risk of a reduction in eGFR by half (hazard ratio 1.81, 95% CI 1.25, 2.62). Thus, in a large multiracial cohort of patients with IgAN, individuals of Pacific Asian origin have a higher risk of progression to ESRD.
Abstract
Neutralization of Omicron subvariants by different bivalent vaccines has not been well evaluated. This study characterizes neutralization against Omicron subvariants in 98 individuals on ...dialysis or with a kidney transplant receiving the BNT162b2 (BA.4/BA.5) or mRNA-1273 (BA.1) bivalent COVID-19 vaccine. Neutralization against Omicron BA.1, BA.5, BQ.1.1, and XBB.1.5 increased by 8-fold one month following bivalent vaccination. In comparison to wild-type (D614G), neutralizing antibodies against Omicron-specific variants were 7.3-fold lower against BA.1, 8.3-fold lower against BA.5, 45.8-fold lower against BQ.1.1, and 48.2-fold lower against XBB.1.5. Viral neutralization was not significantly different by bivalent vaccine type for wild-type (D614G) (P = 0.48), BA.1 (P = 0.21), BA.5 (P = 0.07), BQ.1.1 (P = 0.10), nor XBB.1.5 (P = 0.10). Hybrid immunity conferred higher neutralizing antibodies against all Omicron subvariants. This study provides evidence that BNT162b2 (BA.4/BA.5) and mRNA-1273 (BA.1) induce similar neutralization against Omicron subvariants, even when antigenically divergent from the circulating variant.
Pregnancy Outcomes after Clinical Recovery from AKI Tangren, Jessica Sheehan; Powe, Camille E; Ankers, Elizabeth ...
Journal of the American Society of Nephrology,
05/2017, Letnik:
28, Številka:
5
Journal Article
Recenzirano
Odprti dostop
The effect of clinically recovered AKI (r-AKI) on future pregnancy outcomes is unknown. We retrospectively studied all women who delivered infants between 1998 and 2007 at Massachusetts General ...Hospital to assess whether a previous episode of r-AKI associated with subsequent adverse maternal and fetal outcomes, including preeclampsia. AKI was defined as rise in serum creatinine concentration to 1.5-fold above baseline. We compared pregnancy outcomes in women with r-AKI without history of CKD (eGFR>90 ml/min per 1.73 m
before conception;
=105) with outcomes in women without kidney disease (controls;
=24,640). The r-AKI and control groups had similar prepregnancy serum creatinine measurements (0.70±0.20 versus 0.69±0.10 mg/dl;
=0.36). However, women with r-AKI had increased rates of preeclampsia compared with controls (23% versus 4%;
<0.001). Infants of women with r-AKI were born earlier than infants of controls (37.6±3.6 versus 39.2±2.2 weeks;
<0.001), with increased rates of small for gestational age births (15% versus 8%;
=0.03). After multivariate adjustment, r-AKI associated with increased risk for preeclampsia (adjusted odds ratio aOR, 5.9; 95% confidence interval 95% CI, 3.6 to 9.7) and adverse fetal outcomes (aOR, 2.4; 95% CI, 1.6 to 3.7). When women with r-AKI and controls were matched 1:2 by age, race, body mass index, diastolic BP, parity, and diabetes status, r-AKI remained associated with preeclampsia (OR, 4.7; 95% CI, 2.1 to 10.1) and adverse fetal outcomes (OR, 2.1; 95% CI, 1.2 to 3.7). Thus, a past episode of AKI, despite return to normal renal function before pregnancy, associated with adverse outcomes in pregnancy.
Previous studies have suggested that a patient's sex may influence the provision and outcomes of critical care. Our objective was to determine whether sex and age are associated with differences in ...admission practices, processes of care and clinical outcomes for critically ill patients.
We used a retrospective cohort of 466,792 patients, including 24,778 critically ill patients, admitted consecutively to adult hospitals in Ontario between Jan. 1, 2001, and Dec. 31, 2002. We measured associations between sex and age and admission to the intensive care unit (ICU); use of mechanical ventilation, dialysis or pulmonary artery catheterization; length of stay in the ICU and hospital; and death in the ICU, hospital and 1 year after admission.
Of the 466,792 patients admitted to hospital, more were women than men (57.0% v. 43.0% for all admissions, p < 0.001; 50.1% v. 49.9% for nonobstetric admissions, p < 0.001). However, fewer women than men were admitted to ICUs (39.9% v. 60.1%, p < 0.001); this difference was most pronounced among older patients (age > or = 50 years). After adjustment for admission diagnoses and comorbidities, older women were less likely than older men to receive care in an ICU setting (odds ratio OR 0.68, 95% confidence interval CI 0.66-0.71). After adjustment for illness severity, older women were also less likely than older men to receive mechanical ventilation (OR 0.91, 95% CI 0.81-0.97) or pulmonary artery catheterization (OR 0.80, 95% CI 0.73-0.88). Despite older men and women having similar severity of illness on ICU admission, women received ICU care for a slightly shorter duration yet had a longer length of stay in hospital (mean 18.3 v. 16.9 days; p = 0.006). After adjustment for differences in comorbidities, source of admission, ICU admission diagnosis and illness severity, older women had a slightly greater risk of death in the ICU (hazard ratio 1.20, 95% CI 1.10-1.31) and in hospital (hazard ratio 1.08, 95% CI 1.00-1.16) than did older men.
Among patients 50 years or older, women appear less likely than men to be admitted to an ICU and to receive selected life-supporting treatments and more likely than men to die after critical illness. Differences in presentation of critical illness, decision-making or unmeasured confounding factors may contribute to these findings.
Pregnancies in women with CKD carry greater risk than pregnancies in the general population. The small number of women in prior studies has limited estimates of this risk, especially among those with ...advanced CKD. We report the results of a population-based cohort study in Ontario, Canada, that assessed more than 500,000 pregnancies, including 600 with a baseline eGFR < 60 ml/min per 1.73 m 2 . The investigation demonstrates increases in risk of different adverse maternal and fetal outcomes with lower eGFR and further risk elevation with baseline proteinuria.
CKD is a risk factor for pregnancy complications, but estimates for adverse outcomes come largely from single-center studies with few women with moderate or advanced stage CKD.
To investigate the association between maternal baseline eGFR and risk of adverse pregnancy outcomes, we conducted a retrospective, population-based cohort study of women (not on dialysis or having had a kidney transplant) in Ontario, Canada, who delivered between 2007 and 2019. The study included 565,907 pregnancies among 462,053 women. Administrative health databases captured hospital births, outpatient laboratory testing, and pregnancy complications. We analyzed pregnancies with serum creatinine measured within 2 years of conception up to 30 days after conception and assessed the impact of urine protein where available.
The risk of major maternal morbidity, preterm delivery, and low birthweight increased monotonically across declining eGFR categories, with risk increase most notable as eGFR dropped below 60 ml/min per 1.73 m 2 . A total of 56 (40%) of the 133 pregnancies with an eGFR <45 ml/min per 1.73 m 2 resulted in delivery under 37 weeks, compared with 10% of pregnancies when eGFR exceeded 90 ml/min per 1.73 m 2 . Greater proteinuria significantly increased risk within each eGFR category. Maternal and neonatal deaths were rare regardless of baseline eGFR (<0.3% of all pregnancies). Only 7% of women with an eGFR <45 ml/min per 1.73 m 2 received dialysis during or immediately after pregnancy.
We observed higher rates of adverse pregnancy outcomes in women with low eGFR with concurrent proteinuria. These results can help inform health care policy, preconception counseling, and pregnancy follow-up in women with CKD.
Objectives
Antibody testing against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has been instrumental in detecting previous exposures and analyzing vaccine‐elicited immune responses. ...Here, we describe a scalable solution to detect and quantify SARS‐CoV‐2 antibodies, discriminate between natural infection‐ and vaccination‐induced responses, and assess antibody‐mediated inhibition of the spike‐angiotensin converting enzyme 2 (ACE2) interaction.
Methods
We developed methods and reagents to detect SARS‐CoV‐2 antibodies by enzyme‐linked immunosorbent assay (ELISA). The main assays focus on the parallel detection of immunoglobulin (Ig)Gs against the spike trimer, its receptor binding domain (RBD) and nucleocapsid (N). We automated a surrogate neutralisation (sn)ELISA that measures inhibition of ACE2‐spike or ‐RBD interactions by antibodies. The assays were calibrated to a World Health Organization reference standard.
Results
Our single‐point IgG‐based ELISAs accurately distinguished non‐infected and infected individuals. For seroprevalence assessment (in a non‐vaccinated cohort), classifying a sample as positive if antibodies were detected for ≥ 2 of the 3 antigens provided the highest specificity. In vaccinated cohorts, increases in anti‐spike and ‐RBD (but not ‐N) antibodies are observed. We present detailed protocols for serum/plasma or dried blood spots analysis performed manually and on automated platforms. The snELISA can be performed automatically at single points, increasing its scalability.
Conclusions
Measuring antibodies to three viral antigens and identify neutralising antibodies capable of disrupting spike‐ACE2 interactions in high‐throughput enables large‐scale analyses of humoral immune responses to SARS‐CoV‐2 infection and vaccination. The reagents are available to enable scaling up of standardised serological assays, permitting inter‐laboratory data comparison and aggregation.
We developed scalable serology assays to detect and quantify SARS‐CoV‐2 antibodies, discriminate between natural infection‐ and vaccination‐induced responses, and assess antibody‐mediated inhibition of the spike‐angiotensin converting enzyme 2 (ACE2) interaction. This serology solution enables large‐scale analyses of humoral immune responses to SARS‐CoV‐2 infection and vaccination permitting inter‐laboratory data comparison and aggregation.
H.P. Acthar(®) Gel is currently the only Food and Drug Administration therapy approved for the treatment of nephrotic syndrome. Active drug ingredients include structurally related melanocortin ...peptides that bind to cell surface G-protein-coupled receptors known as melanocortin receptors, which are expressed in glomerular podocytes. In animal models of membranous nephropathy, stimulation has been demonstrated to reduce podocyte injury and loss. We hypothesized that H.P. Acthar(®) Gel would improve symptoms of the nephrotic syndrome in patients with idiopathic membranous nephropathy.
Twenty patients received a subcutaneous dose of 40 or 80 IU twice weekly. Changes in proteinuria, albumin, cholesterol profile, estimated glomerular filtration rate and serum anti-PLA2R antibodies were assessed at baseline and in response to treatment along with tolerance and safety.
Baseline characteristics included mean proteinuria (9.1 ± 3.4 g/day), albumin (2.7 ± 0.8 g/dL), estimated glomerular filtration rate (77 ± 30 mL/min) along with elevated total and low-density lipoprotein (LDL) cholesterol. By 12 months of follow-up, there was a significant improvement in proteinuria in the entire cohort, decreasing to 3.87 ± 4.24 g/day (P < 0.001) with significant improvements in serum albumin, total and LDL cholesterol. A >50% decrease in proteinuria was noted in 65% of the patients with a trend toward better outcomes among patients who received greater cumulative doses. No significant adverse effects were documented. Clearing of serum anti-PLA2R antibodies prior to or in parallel with proteinuria improvement was noted in some, but not all patients.
H.P. Acthar(®) Gel is a potential therapy for nephrotic syndrome secondary to idiopathic membranous nephropathy that deserves further study.
Although early studies suggest that patients with idiopathic membranous nephropathy (MGN) and subnephrotic range proteinuria overall do well, these studies were small and follow-up was short or ...difficult to discern.
Three hundred ninety-five cases of idiopathic MGN with at least 12 mo of follow-up from the Toronto Glomerulonephritis Registry were reviewed to determine the outcome of the subgroup of patients that presented with subnephrotic range proteinuria. Onset and follow-up data included mean arterial pressure (MAP) and creatinine clearance (CrCl) as determined by the Cockcroft-Gault equation. Outcome variables included the rate of progression (slope of CrCl), 50% reduction in initial CrCl, and end-stage renal disease (ESRD).
One hundred eight (27% of the total) patients presented with subnephrotic proteinuria and almost 40% (42 of 108) of this subgroup remained subnephrotic. Their long-term slope was -0.93 ml/min/yr. In contrast, those who subsequently developed nephrotic range proteinuria had a progression rate almost four times faster (-3.52 ml/min/yr). The majority who developed nephrotic syndrome did so within the first year of follow-up. The only distinguishing baseline feature between the two groups was a higher level of urine protein in the group that subsequently developed nephrotic syndrome (1.98 0.3 to 3.4 versus 2.43 0.5 to 3.4 g/d).
Patients with MGN and sustained subnephrotic range proteinuria have an excellent prognosis. Conservative management with close monitoring is recommended given the difficulty predicting which patients will develop nephrotic range proteinuria and then progress more rapidly.
People with advanced CKD are at high risk of mortality and morbidity from coronavirus disease 2019 (COVID-19). We measured rates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ...infection and severe outcomes in a large population attending advanced CKD clinics during the first 21 months of the pandemic. We examined risk factors for infection and case fatality, and we assessed vaccine effectiveness in this population.
In this retrospective cohort study, we analyzed data on demographics, diagnosed SARS-CoV-2 infection rates, outcomes, and associated risk factors, including vaccine effectiveness, for people attending a province-wide network of advanced CKD clinics during the first four waves of the pandemic in Ontario, Canada.
In a population of 20,235 patients with advanced CKD, 607 were diagnosed with SARS-CoV-2 infection over 21 months. The case fatality rate at 30 days was 19% overall but declined from 29% in the first wave to 14% in the fourth. Hospitalization and intensive care unit (ICU) admission rates were 41% and 12%, respectively, and 4% started long-term dialysis within 90 days. Significant risk factors for diagnosed infection on multivariable analysis included lower eGFR, higher Charlson Comorbidity Index, attending advanced CKD clinics for more than 2 years, non-White ethnicity, lower income, living in the Greater Toronto Area, and long-term care home residency. Being doubly vaccinated was associated with lower 30-day case fatality rate (odds ratio OR, 0.11; 95% confidence interval CI, 0.03 to 0.52). Older age (OR, 1.06 per year; 95% CI, 1.04 to 1.08) and higher Charlson Comorbidity Index (OR, 1.11 per unit; 95% CI, 1.01 to 1.23) were associated with higher 30-day case fatality rate.
People attending advanced CKD clinics and diagnosed with SARS-CoV-2 infection in the first 21 months of the pandemic had high case fatality and hospitalization rates. Fatality rates were significantly lower in those who were doubly vaccinated.
This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_04_10_CJN10560922.mp3.
Pregnancy planning in patients with chronic kidney disease can result in ethical conflicts due to the potential for adverse outcomes. Traditionally, many nephrologists have advised their patients to ...avoid pregnancy altogether; however, this approach is paternalistic and not patient-centered. An ethical framework could guide joint decision-making between physicians and their patients, but this does not currently exist.
We performed a literature search to identify the ethical considerations associated with this patient population. We searched for articles published between 1975 and 2019 using the terms “ethics” and “high risk pregnancy,” along with 29 chronic disease-specific MeSH terms. Subsequently, we performed a critical evaluation using established ethical theories and adapted anonymized clinical cases from the Pregnancy in Kidney Disease Clinic (PreKid Clinic) at our institution to guide the discussion.
We identified 968 articles and excluded 947 based on their title or abstract. Twelve full-text articles were included, representing discussions, case reports, and literature reviews on the ethics of pregnancy in 8 chronic diseases. The extracted data were applied to 5 clinical cases to guide the discussion.
This clinical review focuses on 3 main ethical themes: duty to patient, duty to the fetus, and duty to society, to help physicians explore common scenarios that may arise when counseling patients around pregnancy. Primarily, physicians have a duty to facilitate autonomous decision-making and informed consent. Secondarily, they have a duty to protect the fetus and use resources judiciously as long as it does not impact the care of their patients.
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