Nephrotic syndrome is a common glomerular disease in children with significant variability in both incidence and steroid responsiveness among various ethnic groups. The average incidence of nephrotic ...syndrome is 2-16.9 per 100,000 children worldwide. Understanding the variability by ethnicity may point to potential factors leading to nephrotic syndrome, which remains elusive, and may highlight factors accounting for differences in medication response. The emerging role of genetic factors associated with steroid responsive and steroid-resistant forms of nephrotic syndrome within an ethnic group can provide insight into potential biological mechanisms leading to disease. For example, among African-Americans, the risk variants in APOL1 are associated with a more than 10-fold increase in risk of focal segmental glomerulosclerosis and high-risk carriers have a twofold greater risk of progression to end-stage renal disease. Ongoing collaborative studies should consider capturing data on self-reported ethnicity to understand differences in incidence and outcomes. In the future, the availability of whole-genome data will provide an excellent opportunity for new clinical and translational research in childhood nephrotic syndrome and lead to a better understanding of the disease.
Numerous substances accumulate in the body in uremia but those contributing to cardiovascular morbidity and mortality in dialysis patients are still undefined. We examined the association of baseline ...free levels of four organic solutes that are secreted in the native kidney - p-cresol sulfate, indoxyl sulfate, hippurate and phenylacetylglutamine - with outcomes in hemodialysis patients.
We measured these solutes in stored specimens from 394 participants of a US national prospective cohort study of incident dialysis patients. We examined the relation of each solute and a combined solute index to cardiovascular mortality and morbidity (first cardiovascular event) using Cox proportional hazards regression adjusted for demographics, comorbidities, clinical factors and laboratory tests including Kt/VUREA.
Mean age of the patients was 57 years, 65% were white and 55% were male. In fully adjusted models, a higher p-cresol sulfate level was associated with a greater risk (HR per SD increase; 95% CI) of cardiovascular mortality (1.62; 1.17-2.25; p=0.004) and first cardiovascular event (1.60; 1.23-2.08; p<0.001). A higher phenylacetylglutamine level was associated with a greater risk of first cardiovascular event (1.37; 1.18-1.58; p<0.001). Patients in the highest quintile of the combined solute index had a 96% greater risk of cardiovascular mortality (1.96; 1.05-3.68; p=0.04) and 62% greater risk of first cardiovascular event (1.62; 1.12-2.35; p=0.01) compared with patients in the lowest quintile. Results were robust in sensitivity analyses.
Free levels of uremic solutes that are secreted by the native kidney are associated with a higher risk of cardiovascular morbidity and mortality in incident hemodialysis patients.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Nephrotic syndrome is defined by nephrotic-range proteinuria (≥40 mg/m
2
/hour or urine protein/creatinine ratio ≥200 mg/mL or 3+ protein on urine dipstick), hypoalbuminaemia (<25 g/L) and oedema. ...This review focuses on the classification, epidemiology, pathophysiology, management strategies and prognosis of idiopathic nephrotic syndrome of childhood, and includes a brief overview of the congenital forms.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Women of African ancestry are highly predisposed to preeclampsia which continues to be a major cause of maternal death in Africa. Common variants in the APOL1 gene are potent risk factor for a ...spectrum of kidney disease. Recent studies have shown that APOL1 risk variants contribute to the risk of preeclampsia. The aim of the study is to understand the contribution of APOL1 risk variants to the development of preeclampsia in pregnant women in Ghana.
The study is a case-control design which started recruitment in 2019 at the Korle Bu Teaching Hospital in Ghana. The study will recruit pregnant women with a target recruitment of 700 cases of preeclampsia and 700 normotensives. Clinical and demographic data of mother- baby dyad, with biospecimens including cord blood and placenta will be collected to assess clinical, biochemical and genetic markers of preeclampsia. The study protocol was approved by Korle Bu Teaching Hospital Institutional Review Board (Reference number: KBTH-IRB/000108/2018) on October 11, 2018.
As of December 2021, a total of 773 mother-baby pairs had been recruited and majority of them had complete entry of data for analysis. The participants are made up of 384 preeclampsia cases and 389 normotensive mother-baby dyad. The mean age of participants is 30.69 ± 0.32 years for cases and 29.95 ± 0.32 for controls. Majority (85%) of the participants are between 20-30years. At booking, majority of cases had normal blood pressure compared to the time of diagnosis where 85% had a systolic BP greater than 140mmHg and a corresponding 82% had diastolic pressure greater than 90mmHg.
Our study will ultimately provide clinical, biochemical and genotypic data for risk stratification of preeclampsia and careful monitoring during pregnancy to improve clinical management and outcomes.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
For many years, the universally used equation for estimating risk of kidney disease, included an adjustment for Black race that led to an upward correction in estimated glomerular filtration rate ...(eGFR). In 2021, new equations that omit race but include other factors were developed and found to be more accurate in estimating eGFR, and the US National Kidney Foundation, American Society of Nephrology Task Force on Reassessing the Inclusion of Race in Diagnosing Kidney Diseases and the UK National Institute for Health and Care Excellence recommended the removal of race from the calculation of eGFR. Here, Parekh et al discuss why the inclusion of race in kidney function estimates is biased and harmful, and why swift adoption of calculations that omit race is important in clinical care in Canada.
Patients of all ages undergoing hemodialysis (HD) have a high prevalence of cognitive impairment and worse cognitive function than healthy controls, and those with dementia are at high risk of death. ...Frailty has been associated with poor cognitive function in older adults without kidney disease. We hypothesized that frailty might also be associated with poor cognitive function in adults of all ages undergoing HD.
At HD initiation, 324 adults enrolled (November 2008 to July 2012) in a longitudinal cohort study (Predictors of Arrhythmic and Cardiovascular Risk in ESRD) were classified into three groups (frail, intermediately frail, and nonfrail) based on the Fried frailty phenotype. Global cognitive function (3MS) and speed/attention (Trail Making Tests A and B TMTA and TMTB, respectively) were assessed at cohort entry and 1-year follow-up. Associations between frailty and cognitive function (at cohort entry and 1-year follow-up) were evaluated in adjusted (for sex, age, race, body mass index, education, depression and comorbidity at baseline) linear (3MS, TMTA) and Tobit (TMTB) regression models.
At cohort entry, the mean age was 54.8 years (SD 13.3), 56.5% were men, and 72.8% were black. The prevalence of frailty and intermediate frailty were 34.0% and 37.7%, respectively. The mean 3MS was 89.8 (SD 7.6), TMTA was 55.4 (SD 29), and TMTB was 161 (SD 83). Frailty was independently associated with lower cognitive function at cohort entry for all three measures (3MS: -2.4 points; 95% confidence interval 95% CI, -4.2 to -0.5; P=0.01; TMTA: 12.1 seconds; 95% CI, 4.7 to 19.4; P<0.001; and TMTB: 33.2 seconds; 95% CI, 9.9 to 56.4; P=0.01; all tests for trend, P<0.001) and with worse 3MS at 1-year follow-up (-2.8 points; 95% CI, -5.4 to -0.2; P=0.03).
In adult incident HD patients, frailty is associated with worse cognitive function, particularly global cognitive function (3MS).
Steroid sensitive nephrotic syndrome is a common condition in pediatric nephrology, and most children have excellent outcomes. Yet, 50% of children will require steroid-sparing agents due to ...frequently relapsing disease and may suffer consequences from steroid dependence or use of steroid-sparing agents. Several steroid-sparing therapeutic agents are available with few high quality randomized controlled trials to compare efficacy leading to reliance on observational data for clinical guidance. Reported trials focus on short-term outcomes such as time to first relapse, relapse rates up to 1–2 years of follow-up, and few have studied long-term remission. Trial designs often do not consider inter-individual variability, and differing response to treatments may occur due to heterogeneity in pathogenic mechanisms, and genetic and environmental influences. Strategies are proposed to improve the quantity and quality of trials in steroid sensitive nephrotic syndrome with integration of biomarkers, novel trial designs, and standardized outcomes, especially for long-term remission. Collaborative efforts among international trial networks will help move us toward a shared goal of finding a cure for children with nephrotic syndrome.
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