The KDIGO (Kidney Disease: Improving Global Outcomes) clinical practice guideline for management of glomerulonephritis was recently released. The Canadian Society of Nephrology convened a working ...group to review the recommendations and comment on their relevancy and applicability to the Canadian context. A subgroup of adult nephrologists reviewed the guideline statements for management of glomerular disease in adults and agreed with most of the guideline statements developed by KDIGO. This commentary highlights areas for which there is lack of evidence and areas in need of translation of evidence into clinical practice. Areas of controversy or uncertainty, including the choice of second-line agents, are discussed in more detail. Existing practice variation also is addressed. The relevance of treatment recommendations to the Canadian practitioner is discussed.
Abstract Purpose Acute kidney injury is common in intensive care units and is associated with increased morbidity and mortality. We evaluated the ability of whole-blood neutrophil ...gelatinase-associated lipocalin (wbNGAL) to predict mortality and need for renal replacement therapy (RRT) in critically ill patients with kidney dysfunction. Methods We prospectively enrolled adult patients in 5 Canadian intensive care units. We measured wbNGAL at the time of enrollment to determine whether NGAL concentration could predict the primary composite outcome of death or need for RRT by day 30 in addition to other secondary outcomes. Results We recruited 234 patients; 227 were included in the analysis. In a multivariable model, wbNGAL did not predict 30-day mortality or need for RRT (odds ratio, 1.05; 95% confidence interval, 0.99-1.12). Neutrophil gelatinase-associated lipocalin was similar in patients who died (654 303-1180 ng/mL) vs those who survived (541.5 255.5-1080 ng/mL, P = .26) by 90 days. Whole-blood NGAL poorly predicted the primary outcome (area under receiver operator curve, 0.65; 95% confidence interval, 0.58-0.73). Conclusions In a cohort of critically ill patients with abnormal kidney function, wbNGAL was not effective in the prediction of death or RRT within 30 days. These data do not support the use of this biomarker for the detection of clinical outcomes in this population.
To analyze the clinical features and to identify factors associated with the development of Raynaud's phenomenon (RP) in patients receiving chemotherapy for human immunodeficiency virus (HIV) related ...Kaposi's sarcoma.
A retrospective cohort study of all patients with Kaposi's sarcoma treated with chemotherapy at Toronto-Sunnybrook Regional Cancer Centre from 1987 to 1995. Patients who developed RP were compared with those who did not with respect to age, CD4 cell count, Acquired Immune Deficiency Syndrome Clinical Trials Group (ACTG) stage, smoking history, type and dose of chemotherapy, and previous treatment with interferon and radiation therapy.
Eighty-seven patients with Kaposi's sarcoma were treated with chemotherapy between 1987 and 1995. Five developed RP, which progressed to digital gangrene. Median age, proportion of smokers, proportion defined as ACTG poor risk, median CD4 count, and history of opportunistic infections were equal in the 2 groups. All patients with RP received vinblastine followed by bleomycin. No cases of RP occurred in 27 patients treated with vinblastine alone or in 24 patients treated with bleomycin without previous vinblastine. Patients developing RP tended to have received higher cumulative doses of chemotherapy including bleomycin (p = 0.067) and previous treatment with either local radiation or interferon (p < 0.009, p < 0.001, respectively).
Sequential chemotherapy with vinblastine followed by bleomycin was associated with the development of RP in patients with HIV related Kaposi's sarcoma. Bleomycin alone was not associated with RP.
Acute renal failure remains a common, devastating complication of the postoperative period and in the critically ill patient. The most common cause is the progression of prerenal insufficiency to ...ATN. Despite improved understanding of the pathogenic mechanisms, including impaired hemodynamic autoregulation, medullary hypoxia, and proximal tubular obstruction and transtubular backleak, the treatment, to date, remains largely supportive. Avoidance by ensuring hemodynamic stability, with provision of adequate renal perfusion, provides the best means for minimizing the complications of this organ dysfunction.
Focal segmental glomerulosclerosis (FSGS) is an important cause of nondiabetic chronic kidney disease (CKD). Sodium-glucose cotransporter 2 inhibition (SGLT2i) therapy attenuates the progression of ...diabetic nephropathy, but it remains unclear whether SGLT2i provides renoprotection in nondiabetic CKD such as FSGS. The primary aim of this pilot study was to determine the effect of 8 wk of dapagliflozin on glomerular filtration rate (GFR) in humans and in experimental FSGS. Secondary end points were related to changes in renal hemodynamic function, proteinuria, and blood pressure (BP). GFR (inulin) and renal plasma flow (para-aminohippurate), proteinuria, and BP were measured in patients with FSGS ( n = 10), and similar parameters were measured in subtotally nephrectomized (SNx) rats. In response to dapagliflozin, changes in GFR, renal plasma flow, and 24-h urine protein excretion were not statistically significant in humans or rats. Systolic BP (SBP) decreased in SNx rats (196 ± 26 vs. 165 ± 33 mmHg; P < 0.001), whereas changes were not statistically significant in humans (SBP 112.7 ± 8.5 to 112.8 ± 11.2 mmHg, diastolic BP 71.8 ± 6.5 to 69.6 ± 8.4 mmHg; P = not significant), although hematocrit increased (0.40 ± 0.05 to 0.42 ± 0.05%; P = 0.03). In archival kidney tissue from a separate patient cohort, renal parenchymal SGLT2 mRNA expression was decreased in individuals with FSGS compared with controls. Short-term treatment with the SGLT2i dapagliflozin did not modify renal hemodynamic function or attenuate proteinuria in humans or in experimental FSGS. This may be related to downregulation of renal SGLT2 expression. Studies examining the impact of SGLT2i on markers of kidney disease in patients with other causes of nondiabetic CKD are needed.
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.
Acute kidney injury (AKI) is a rare complication of pregnancy, but may be associated with significant morbidity and mortality in young and often otherwise healthy women. We conducted a retrospective ...population-based cohort study of all consecutive pregnancies over a 15-year period (1997-2011) in Ontario, Canada, and describe the incidence and outcomes of AKI treated with dialysis during pregnancy or within 12 weeks of delivery. Of 1,918,789 pregnancies, 188 were complicated by AKI treated with dialysis (incidence: 1 per 10,000 95% confidence interval, 0.8 to 1.1). Only 21 of 188 (11.2%) women had record of a preexisting medical condition; however, 130 (69.2%) women experienced a major pregnancy-related complication, including preeclampsia, thrombotic microangiopathy, heart failure, sepsis, or postpartum hemorrhage. Eight women died (4.3% versus 0.01% in the general population), and seven (3.9%) women remained dialysis dependent 4 months after delivery. Low birth weight (<2500 g), small for gestational age, or preterm birth (<37 weeks' gestation) were more common in pregnancies in which dialysis was initiated (35.6% versus 14.0%; relative risk, 3.40; 95% confidence interval, 2.52 to 4.58). There were no stillbirths and fewer than five neonatal deaths (<2.7%) in affected pregnancies compared with 0.1% and 0.8%, respectively, in the general population. In conclusion, AKI treated with dialysis during pregnancy is rare and typically occurs in healthy women who acquire a major pregnancy-related medical condition such as preeclampsia. Many affected women and their babies have good short-term outcomes.
BACKGROUNDHemodialysis patients exhibit variable immunogenicity following administration of the SARS-CoV-2 mRNA vaccine. The aim of the current study was to evaluate the use of two commercial assays ...in the assessment of SARS-CoV-2 antibody response in hemodialysis patients and to compare their utility to commonly used SARS-CoV-2 serological assays developed in Canada.METHODSWe evaluated serologic antibody response in 85 hemodialysis patients up to 6 months after receiving both doses of the Pfizer-BioNTech BNT162b2 COVID-19 mRNA vaccine. In addition, antibody response was assessed in 46 chronic kidney disease patients and 40 COVID-19 naïve health care workers (HCW) up to 3 months and 9 months, respectively. Anti-spike (S) and anti-nucleocapsid (N) levels were measured using Elecsys anti-SARS-CoV-2 immunoassays on the Roche analyzer and compared to ELISA-based detection of anti-S, anti-receptor binding domain (RBD), and anti-N.RESULTSThe Elecsys anti-N immunoassay showed 93 % concordance with the anti-N ELISA. The Elecsys anti-S immunoassay showed 97 % concordance with the anti-S ELISA and 89 % concordance with the anti-RBD ELISA. HCWs exhibited significantly higher anti-S levels relative to hemodialysis patients. Anti-S levels decreased significantly over a 6-month period (p < 0.001) in patients receiving maintenance hemodialysis. In addition, anti-S levels decreased significantly over a 9-month (p < 0.001) and 3-month period (p < 0.001) in HCWs and CKD patients, respectively.CONCLUSIONSThere is high concordance between commercial SARS-CoV-2 serological assays and SARS-CoV-2 serological assays developed in Canada. Hemodialysis patients exhibited varying immunogenicity following two doses of the COVID-19 mRNA vaccine with anti-S levels decreasing over time.
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