Nephrology

While there are treatments available to help with the symptoms of APOL1-mediated kidney disease, there are currently no approved treatments that address the underlying cause. This type of kidney disease also runs in the family. Therefore, clinical research is essential to try to find a potential treatment that addresses the underlying cause and improves the quality of life of people who are living with kidney problems and to potentially benefit future generations.

This clinical research study is assessing the safety of potential treatment and how well it treats APOL1-mediated kidney disease. It will help increase our knowledge of chronic kidney disease and potentially create treatments for future generations.

Can I take part?

If you have chronic kidney disease and are over the age of 18, you may be able to take part in a new study that can potentially create a treatment for people who are impacted by chronic kidney disease.

Click here if you are interested in learning more (add REDCap link)

Nephrotic syndrome is the most commonly acquired kidney disease in childhood and progressive forms result in complete scarring of the kidney leading to end stage renal disease (ESRD). Nephrotic syndrome is a common clinical presentation of a number of disease processes that appear to have both immune and nonimmune factors leading to disease presentation and disease progression. Current care includes steroids and other immunosuppressive medication, however, there are children that have progressive kidney disease despite medical therapy and appear to be resistant to current immunotherapy as result of non-immune mediated disease.

Aim 1: Develop a pediatric disease-based clinical cohort of children ages 1-18 with nephrotic syndrome and prospectively follow them to determine short- and long-term outcomes including frequent relapses, steroid responsiveness, and progressive kidney disease (In Progress) We hypothesize that the incidence of relapses, steroid unresponsiveness and progressive kidney disease will differ: 1. By ethnicity with South Asians having a higher rate compared to those with European ancestry, 2. By age, with younger children having a higher rate compared to adolescents, 3. By gender, with males having a higher rate compared to females.

Aim 2: Determine if factors (demographic, genetic, serologic, or environmental) are associated with higher risk of frequent relapses of nephrotic syndrome, lack of steroid responsiveness, and progressive kidney disease in cross sectional and prospective analyses. We hypothesize that: 1. Family history of kidney disease will be associated with higher risk, 2. Elevated blood pressure will be associated with higher risk, 3. Total cholesterol will be associated with higher risk. 4. Heavy metal exposure will be associated with higher risk.

Aim 3: Determine if the gene, MYH9, and other Mendelian nephrotic syndrome genes are associated with frequent relapses of nephrotic syndrome, steroid responsiveness and progressive kidney disease in children.

Long-term survival in childhood solid organ transplants

Paediatric solid organ transplant is a successful treatment for solid organ failure with prolonged graft and recipient survival over the past decade. Even though over 80 per cent of paediatric transplant recipients enjoy long-term survival into adolescence and adulthood, the risk of comorbid conditions increases over time given the very long-term exposure to transplant medications, primary end-organ disease and likely repeated transplants over their lifetime. We created a longitudinal paediatric Toronto transplant cohort study with up to 25 years of follow-up. We will create a data repository of information during transplant follow-up at The Hospital for Sick Children (SickKids) and link to available administrative databases at the Institute for Clinical Evaluative Sciences for over 1,000 children with a solid organ transplant performed at SickKids.

We aim to study:

1. the absolute risk of diabetes, hypertension, CVD, CKD, malignancy, and mortality;
2. the relative risk of outcomes to an age and sex-matched general population in Ontario; and
3. the direction, magnitude and strength of association for modifiable risk factors and development of morbidities and mortality across organ groups.

The results from this study may be used as the basis of new clinical recommendations for screening children with a solid organ transplant, treatment and lifestyle modifications to minimize the risk of subsequent morbidity and mortality.

Predictors of Arrhythmic and Cardiovascular Risk in End Stage Renal Disease

PACE was a prospective cohort study that enrolled 568 persons with end-stage renal disease (ESRD) initiating hemodialysis. Participants were recruited in Baltimore and the surrounding area (U.S.) from November 2008 to August 2012. In addition to complete baseline evaluations, participants were actively followed for up to four years during which time data from clinic and phone questionnaires, study visits, cardiovascular assessments, and biological specimens were collected. Recently, data from these participants were linked with the United States Renal Data System to obtain long-term outcomes.

The primary objectives of this study were to identify the rate of sudden cardiac death among adults initiating hemodialysis and to determine risk factors associated with arrhythmias and sudden cardiac death.

Data collection was completed in 2016 and linkage with the United States Renal Data System was established in 2018. To date, the study has identified a number of risk factors for sudden cardiac death including spatial QRS-T angle and abdominal obesity.

H3Africa is a consortium that conducts fundamental research into diseases on the African continent. The consortium is also helping to develop infrastructure, resources, training, and ethical guidelines to support a sustainable African research enterprise.

The initiative consists of 48 African projects that include population-based genomic studies of common, non-communicable disorders such as heart and renal disease, as well as communicable diseases such as tuberculosis and trypanosomiasis.

To date, H3Africa has secured funding for the period of 2011-2021 from the U.S. National Institutes of Health, the African Academy of Sciences, and the Wellcome Trust. Numerous training programs have been launched to educate participants on topics ranging from Python programming, to best practices in molecular biology, to bioinformatics. The research conducted by consortium members has provided, inter alia, critical insight into the risk factors for stroke in West Africa, antimicrobial resistance in pneumococci, drug sensitivity in tuberculosis in Ethiopia, and the influence of human breast milk microbiome in South African Women.

Family History of Nephropathy and Diabetes

Family Investigation of Nephropathy and Diabetes (FIND) was a multicentre observational study of multi-ethnic participants recruited from 11 centres across the USA between 1999 and 2004. Data were collected until 2007. A genome-wide association study (GWAS) was conducted to identify genetic determinants of diabetic kidney disease.

The primary aim of the FIND study was to identify genes responsible for diabetic nephropathy and whether these genes exhibit linkage relationships to nephropathy. A secondary aim was to use environmental data as a guide for determining possible risk factor effects on genetic susceptibility to diabetic nephropathy. As part of FIND, a biobank was created to store biological samples collected from participants for use in future studies related to diabetes and kidney diseases.

Data collection for the FIND study was completed in 2007. With these data, several genes associated with diabetic nephropathy, albuminuria, and GFR were identified. Notably, MYH9 was found to be associated with nondiabetic end-stage renal disease in African Americans.