2024-25 Project (Nitsch & Filteau & Fatumo)

The association of malnutrition and infections with acute and chronic kidney disease

SUPERVISORY TEAM

Supervisor

Professor Dorothea Nitsch at LSHTM
Email: dorothea.nitsch@lshtm.ac.uk

Co-Supervisor

Professor Suzanne Filteau at LSHTM
Email: suzanne.filteau@lshtm.ac.uk

Co-Supervisor

Associate Professor Segun Fatumo at LSHTM
Email: segun.fatumo@lshtm.ac.uk

PROJECT SUMMARY

Project Summary  

Acute kidney injury (AKI) represents a sudden loss of kidney function as a result of severe health event, most commonly life threatening infections. Recent research in high income settings has shown that people who have suffered AKI are much more likely to have later chronic kidney disease (CKD) and overall higher mortality.   If these findings generalise to low and middle income settings the implications are severe in terms of the kidney health of populations in these settings. This is because the chance of a person being admitted with a serious infection to hospital are far higher (given the overall higher burden of infections). We also know that malnourished children are at high risk of having infections, but data are scarce on whether malnutrition puts person at higher risk of acute kidney injury and potentially worse kidney health.   A complicating factor is that measurement of kidney function using conventional clinical markers may not work well in the context of malnutrition and low muscle mass which will have led to underappreciation of the extent of kidney disease in this context.   This PhD aims to get at these questions.  

Firstly, a systematic review will pool relevant literature on the prevalence of malnutrition amongst people presenting with acute kidney injury. Data on muscle mass will be correlated with the error in kidney function measurement using gold-standard data from the ARK study. The SAMPA study is a multinational cohort study of people who did or did not experience severe acute malnutrition in the past which will allow to quantify the overall effect of severe acute malnutrition on kidney function markers. A genetic analysis can investigate whether people who reached a lower adult height and who have variants of the ApoL1 gene which predisposes to kidney disease in the context of acute environmental triggers (e.g HIV, other viral infections) are more likely to have reduced kidney function and/or albuminuria using the GPC dataset.

Project Key Words

Kidney function, malnutrition, secondary data analysis, non-communicable diseases

MRC LID Themes

  • Global Health = Yes
  • Health Data Science = Yes
  • Infectious Disease = Yes
  • Translational and Implementation Research = Yes

Skills

MRC Core Skills

  • Quantitative skills = Yes
  • Interdisciplinary skills = Yes
  • Whole organism physiology = Yes

Skills we expect a student to develop/acquire whilst pursuing this project

Systematic review skills 
Validation study skills/biomarker assessment 
Analytic skills  
Analysing multi-country datasets 
Genetic analyses

Routes

Which route/s is this project available for?

  • 1+4 = Yes
  • +4 = Yes

Possible Master’s programme options identified by supervisory team for 1+4 applicants:

  • LSHTM – MSc Epidemiology
  • LSHTM – MSc Medical Statistics

Full-time/Part-time Study

Is this project available for full-time study? Yes
Is this project available for part-time study? Yes

Eligibility/Requirements

Particular prior educational requirements for a student undertaking this project

  • LSHTM’s standard institutional eligibility criteria for doctoral study.
  • MSc in epidemiology or statistics or an MSc in a related topic (global health, nutrition) which had a large component of statistics and epidemiology

Other useful information

  • Potential CASE conversion? = No

PROJECT IN MORE DETAIL

Scientific description of this research project

This project will use secondary data analyses to quantify the infection- and malnutrition related burden of acute and chronic kidney disease in low- and middle income settings.  

Project objectives:   
1. To carry out a systematic review of prevalence of malnutrition in people presenting with acute kidney injury in LMIC settings. 
2. To quantify the association of lean muscle mass, body mass index with measurement error of kidney function estimation using biomarkers (serum creatinine, serum cystatin C) compared to gold standard iohexol measurements.(secondary analysis of the ARK study) 
3. To investigate the association of a history of severe acute malnutrition on biomarkers of kidney function (secondary analysis of SAMPA study) 
4. To investigate the association of kidney function markers with pancreatic endocrine and exocrine function (secondary analysis of SAMPA study) 
5. To carry out gene-environment analysis of ApoL1 mutations and adult height on kidney function using data from the MRC Uganda held GPC study.    

Techniques to be used. 
Systematic review skills 
Validation study of using biomarkers 
Analyses of a complex international cohort studies (both ARK and SAMPA pool data from a range of cohorts in several countries)  
Potential visit to overseas institutions where the data were collected in order to gain contextual experience 
Genetic analyses   

Confirmed availability of data.
The first supervisor is a Co-I on both ARK and SAMPA studies. The second supervisor is the main PI of the SAMPA study. The third supervisor is a genetic epidemiologist based at MRC Uganda.  Members of the ARK leadership team (Robert Kalyesubula, June Fabian) will be members of the advisory board.    

Potential risks to the project/mitigation. 
Systematic review: limited data. We can change the topic if required. The data for quantitative analysis is already collected or in the process of being collected and access will be possible so the other parts of the project have no real risks. Analyses of genetic data will use secondary data from Dr Fatumo’s ongoing Wellcome funded work on investigating genetic risk factors for kidney disease in Sub-Saharan Africa.

Further reading

(Relevant preprints and/or open access articles)

Additional information from the supervisory team

  • The supervisory team has provided a recording for prospective applicants who are interested in their project. This recording should be watched before any discussions begin with the supervisory team.
    Nitsch-Filteau-Fatumo Recording

MRC LID LINKS