The risk of venous thromboembolic events is thought to be highest in patients with membranous nephropathy. This association has been recently questioned, and it is not known whether this simply reflects the severity of proteinuria. To better understand the relationship between histologic diagnosis and the risk of venous thromboembolic events we evaluated patients in the Toronto Glomerulonephritis Registry. Of 1313 patients with idiopathic glomerulonephritis, 395 were diagnosed with membranous nephropathy, 370 with focal segmental glomerulosclerosis (FSGS), and 548 with immunoglobulin-A nephropathy (IgAN). Risk factors were evaluated by Cox proportional hazards for 53 image-confirmed venous thromboembolic events in 44 patients during a median follow-up of 63 months. The risk was highest in patients with membranous nephropathy and FSGS (hazard ratios of 22 and 7.8, respectively) referenced to patients with IgAN. Following adjustment for gender, cancer history, proteinuria, and serum albumin by multivariable analysis, the histologic subtype remained an independent risk for venous thromboembolic events. This risk was still highest in patients with membranous nephropathy followed by FSGS with adjusted hazard ratios of 10.8 and 5.9, respectively. Thus, in this large cohort, histologic diagnosis was an independent risk factor for venous thromboembolic events. Further studies are needed to discover mechanisms responsible for this high risk in patients with membranous nephropathy.
1] Division of Nephrology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada  British Columbia Provincial Renal Agency, Vancouver, British Columbia, Canada  Toronto Glomerulonephritis Registry, University Health Network, Toronto, Ontario, Canada.
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 59.6 ml/min/1.73 m(2), and median proteinuria was 1.8 g/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 1.62 ml/min/1.73 m(2)/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.
Department of Medicine, Division of Nephrology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada; Department of Medicine, Division of Nephrology, University Health Network, University of Toronto, Toronto, Ontario, Canada; email@example.com.
Pregnancy is rare in women with ESRD and when it occurs, it is often accompanied by significant maternal and fetal morbidity and even mortality. Preliminary data from the Toronto Nocturnal Hemodialysis Program suggested that increased clearance of uremic toxins by intensified hemodialysis improves pregnancy outcomes, but small numbers and the absence of a comparator group limited widespread applicability of these findings. We compared pregnancy outcomes from 22 pregnancies in the Toronto Pregnancy and Kidney Disease Clinic and Registry (2000-2013) with outcomes from 70 pregnancies in the American Registry for Pregnancy in Dialysis Patients (1990-2011). The primary outcome was the live birth rate and secondary outcomes included gestational age and birth weight. The live birth rate in the Canadian cohort (86.4%) was significantly higher than the rate in the American cohort (61.4%; P=0.03). Among patients with established ESRD, the median duration of pregnancy in the more intensively dialyzed Toronto cohort was 36 weeks (interquartile range, 32-37) compared with 27 weeks (interquartile range, 21-35) in the American cohort (P=0.002). Furthermore, a dose response between dialysis intensity and pregnancy outcomes emerged, with live birth rates of 48% in women dialyzed =20 hours per week and 85% in women dialyzed >36 hours per week (P=0.02), with a longer gestational age and greater infant birth weight for women dialyzed more intensively. Pregnancy complications were few and manageable. We conclude that pregnancy may be safe and feasible in women with ESRD receiving intensive hemodialysis.
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.
Advances in immunotherapy have improved survival of patients with systemic lupus erythematosus who now face an increasing burden of chronic diseases including that of the kidney. As systemic inflammation is also thought to contribute directly to the progression of chronic kidney disease (CKD), we assessed this risk in patients with lupus, with and without a diagnosis of nephritis, and also identified modifiable risk factors. Accordingly, we enrolled 631 patients (predominantly Caucasian), of whom 504 were diagnosed with lupus within the first year and followed them an average of 11 years. Despite the presence of a chronic inflammatory disease, the rate of decline in renal function of 238 patients without nephritis was similar to that described for non-lupus patient cohorts. Progressive loss of kidney function developed exclusively in patients with lupus nephritis who had persistent proteinuria and dyslipidemia, although only six required dialysis or transplantation. The mortality rate was 16% with half of the deaths attributable to sepsis or cancer. Thus, despite the presence of a systemic inflammatory disease, the risk of progressive CKD in this lupus cohort was relatively low in the absence of nephritis. Hence, as in idiopathic glomerular disease, persistent proteinuria and dyslipidemia (modifiable risks) are the major factors for CKD progression in lupus patients with renal involvement.
Acute kidney injury frequently arises within an acute care hospitalization. Outcomes among acute kidney injury survivors following hospital discharge are poorly documented.
We conducted a population-based cohort study between 1996 and 2006 of all adult patients in Ontario with acute kidney injury who did not require in-hospital dialysis, and who survived free of dialysis =30 days after discharge. Those with acute kidney injury (n=41,327) were matched 1:1 to patients without acute kidney injury during their index hospitalization. Matching was by age (±1 year), sex, history of chronic kidney disease, receipt of mechanical ventilation during the index hospitalization, and a propensity score for developing acute kidney injury. The primary outcome was subsequent need for chronic dialysis. The secondary outcomes were all-cause mortality and rehospitalization.
Mean age was 70 years, and median follow-up was 2 years (maximum 10 years). The incidence of chronic dialysis was 1.78 per 100 person-years among those with acute kidney injury and 0.74 per 100 person-years among unaffected controls (adjusted hazard ratio [HR]; 2.70, 95% confidence interval [CI], 2.42-3.00). Rates also were higher for all-cause mortality (15.34 vs 14.51 per-100 person-years; adjusted HR 1.10; 95% CI, 1.07-1.13) and rehospitalization (44.93 vs 37.18 per 100 person-years; adjusted HR 1.21; 95% CI, 1.18-1.24).
Even when acute dialysis is not required, survivors of acute kidney injury remain at higher risk of receipt of chronic dialysis thereafter. The absolute risk of death was more than 8 times the rate of chronic dialysis.
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 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.
Cites: J Am Coll Cardiol. 2002 Jun 19;39(12):1909-1612084587
Cites: Crit Care Med. 2005 Dec;33(12):2786-9316352961
The Oxford classification of IgA nephropathy (IgAN) identified four pathological elements that were of prognostic value and additive to known clinical and laboratory variables in predicting patient outcome. These features are segmental glomerulosclerosis/adhesion, mesangial hypercellularity, endocapillary proliferation, and tubular atrophy/interstitial fibrosis. Here, we tested the Oxford results using an independent cohort of 187 adults and children with IgAN from 4 centers in North America by comparing the performance of the logistic regression model and the predictive value of each of the four lesions in both data sets. The cohorts had similar clinical and histological findings, presentations, and clinicopathological correlations. During follow-up, however, the North American cohort received more immunosuppressive and antihypertensive therapies. Identifying patients with a rapid decline in the rate of renal function using the logistic model from the original study in the validation data set was good (c-statistic 0.75), although less precise than in the original study (0.82). Individually, each pathological variable offered the same predictive value in both cohorts except mesangial hypercellularity, which was a weaker predictor. Thus, this North American cohort validated the Oxford IgAN classification and supports its utilization. Further studies are needed to determine the relationship to the impact of treatment and to define the value of the mesangial hypercellularity score.