Chronic kidney disease of unknown etiology in Central America and Sri Lanka : renal morphology and clinical characteristics
Author: Wijkström, Julia
Date: 2017-09-28
Location: Föreläsningssal M41, Karolinska Universitetssjukhuset, Flemingsberg
Time: 09.30
Department: Inst för klinisk vetenskap, intervention och teknik / Dept of Clinical Science, Intervention and Technology
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Thesis (5.115Mb)
Abstract
Background: Chronic kidney disease (CKD) is a global health problem. The most common etiologies
of CKD are diabetes mellitus, hypertension, and glomerulonephritis, but over the last several decades
a high prevalence of CKD of unknown etiology (CKDu) has been reported from rural communities in
some tropical countries, including Central America, and Sri Lanka. The CKDu endemics share some
mutual characteristics, they usually affect rural communities and men are more often affected than
women. In Central America, the disease often affects male sugarcane workers. In Sri Lanka, male rice
farmers in certain areas are at risk of developing CKDu. The cause or causes behind the CKDu
endemics have not been elucidated. Furthermore, it has not been determined whether the two
endemics are similar diagnostic entities. Kidney biopsy is an important tool to evaluate CKD, but in
Central America, biopsy studies from patients with CKDu were lacking at the beginning of our
studies.
Aim: The aims were to describe the renal morphology and biochemical characteristics in patients with CKDu in Central America and Sri Lanka in order to find pathogenetic mechanisms, to study the natural history of the disease, and to compare the endemics to determine if they are related diagnostic entities.
Material and Methods: Patients with CKDu were evaluated with kidney biopsy, biochemical tests and a questionnaire. Light- and electron microscopy as well as immunofluorescence evaluation were performed on the biopsies. Follow-up blood and urine samples were collected from subjects in Studies I and II after 1-2.5 years.
Study I: Eight male agricultural workers in El Salvador with an estimated glomerular filtration rate (eGFR) between 27-79 ml/min/1.73m² were included. The kidney biopsies showed a unique renal morphology with extensive glomerulosclerosis, signs of glomerular ischemia, mild to moderate tubular atrophy, and interstitial fibrosis. Vascular structures were generally only mildly changed. In serum, low potassium levels were a common finding.
Study II: Nineteen males from Nicaragua with a history of sugarcane work were included. eGFR was between 33-96 ml/min/1.73m² and low serum sodium, potassium, and magnesium were frequent findings. Sixteen biopsies were representative and the morphology displayed chronic glomerular changes with glomerulosclerosis, glomerular hypertrophy, and signs of glomerular ischemia. Mild to moderate tubulointerstitial changes and mostly mild vascular changes were found. Follow-up samples from 7 participants from Study I and 18 participants from Study II showed a mean eGFR change of -4.4 ± 8.4 ml/min/1.73m² per year.
Study III: Eleven male rice farmers from Sri Lanka with an eGFR between 21-70 ml/min/1.73m² were included. Again, low sodium, potassium, and magnesium were common. The main biopsy findings were chronic glomerular changes (glomerulosclerosis, glomerular hypertrophy) and mild to moderate tubulointerstitial changes. Vascular changes were in most cases mild but in a few cases moderate. The biopsies showed a more mixed morphology compared to Studies I and II. Interstitial inflammation and vascular pathology were more frequent.
Conclusions: Studies I and II show that CKDu in Central America is a unique diagnostic entity with a renal morphology characterized by chronic damage in both glomerular and tubulointerstitial compartments. Although Study III in Sri Lanka revealed a more mixed kidney biopsy morphology, the majority of the subjects had a morphology quite similar to the findings in Central America. Low levels of serum electrolytes were a typical finding in all studies. In summary, CKDu in Sri Lanka and Central America have more similarities than differences in both the morphological and the biochemical characteristics, which supports the theory that the endemics have a common etiology.
Aim: The aims were to describe the renal morphology and biochemical characteristics in patients with CKDu in Central America and Sri Lanka in order to find pathogenetic mechanisms, to study the natural history of the disease, and to compare the endemics to determine if they are related diagnostic entities.
Material and Methods: Patients with CKDu were evaluated with kidney biopsy, biochemical tests and a questionnaire. Light- and electron microscopy as well as immunofluorescence evaluation were performed on the biopsies. Follow-up blood and urine samples were collected from subjects in Studies I and II after 1-2.5 years.
Study I: Eight male agricultural workers in El Salvador with an estimated glomerular filtration rate (eGFR) between 27-79 ml/min/1.73m² were included. The kidney biopsies showed a unique renal morphology with extensive glomerulosclerosis, signs of glomerular ischemia, mild to moderate tubular atrophy, and interstitial fibrosis. Vascular structures were generally only mildly changed. In serum, low potassium levels were a common finding.
Study II: Nineteen males from Nicaragua with a history of sugarcane work were included. eGFR was between 33-96 ml/min/1.73m² and low serum sodium, potassium, and magnesium were frequent findings. Sixteen biopsies were representative and the morphology displayed chronic glomerular changes with glomerulosclerosis, glomerular hypertrophy, and signs of glomerular ischemia. Mild to moderate tubulointerstitial changes and mostly mild vascular changes were found. Follow-up samples from 7 participants from Study I and 18 participants from Study II showed a mean eGFR change of -4.4 ± 8.4 ml/min/1.73m² per year.
Study III: Eleven male rice farmers from Sri Lanka with an eGFR between 21-70 ml/min/1.73m² were included. Again, low sodium, potassium, and magnesium were common. The main biopsy findings were chronic glomerular changes (glomerulosclerosis, glomerular hypertrophy) and mild to moderate tubulointerstitial changes. Vascular changes were in most cases mild but in a few cases moderate. The biopsies showed a more mixed morphology compared to Studies I and II. Interstitial inflammation and vascular pathology were more frequent.
Conclusions: Studies I and II show that CKDu in Central America is a unique diagnostic entity with a renal morphology characterized by chronic damage in both glomerular and tubulointerstitial compartments. Although Study III in Sri Lanka revealed a more mixed kidney biopsy morphology, the majority of the subjects had a morphology quite similar to the findings in Central America. Low levels of serum electrolytes were a typical finding in all studies. In summary, CKDu in Sri Lanka and Central America have more similarities than differences in both the morphological and the biochemical characteristics, which supports the theory that the endemics have a common etiology.
List of papers:
I. Wijkström J, Leiva R, Elinder CG, Leiva S, Trujillo Z, Trujillo L, Söderberg M, Hultenby K, Wernerson A. Clinical and Pathological Characterization of Mesoamerican Nephropathy: A New Kidney Disease in Central America. American Journal of Kidney Diseases. 2013; 62(5): 908-918.
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II. Wijkström J, González-Quiroz M, Hernandez M, Trujillo Z, Hultenby K, Ring A, Söderberg M, Aragon A, Elinder CG, Wernerson A. Renal Morphology, Clinical Findings, and Progression Rate in Mesoamerican Nephropathy. American Journal of Kidney Diseases. 2017; 69(5): 626-636.
Fulltext (DOI)
Pubmed
View record in Web of Science®
III. Wijkström J, Jayasumana C, Dassanayake R, Priyawardane N, Godakanda N, Siribaddana S, Ring A, Hultenby K, Söderberg M, Elinder CG, Wernerson A. Morphological and Clinical Findings in Sri Lankan Patients with Chronic Kidney Disease of Unknown Cause (CKDu): Similarities and Differences with Mesoamerican Nephropathy. [Submitted]
I. Wijkström J, Leiva R, Elinder CG, Leiva S, Trujillo Z, Trujillo L, Söderberg M, Hultenby K, Wernerson A. Clinical and Pathological Characterization of Mesoamerican Nephropathy: A New Kidney Disease in Central America. American Journal of Kidney Diseases. 2013; 62(5): 908-918.
Fulltext (DOI)
Pubmed
View record in Web of Science®
II. Wijkström J, González-Quiroz M, Hernandez M, Trujillo Z, Hultenby K, Ring A, Söderberg M, Aragon A, Elinder CG, Wernerson A. Renal Morphology, Clinical Findings, and Progression Rate in Mesoamerican Nephropathy. American Journal of Kidney Diseases. 2017; 69(5): 626-636.
Fulltext (DOI)
Pubmed
View record in Web of Science®
III. Wijkström J, Jayasumana C, Dassanayake R, Priyawardane N, Godakanda N, Siribaddana S, Ring A, Hultenby K, Söderberg M, Elinder CG, Wernerson A. Morphological and Clinical Findings in Sri Lankan Patients with Chronic Kidney Disease of Unknown Cause (CKDu): Similarities and Differences with Mesoamerican Nephropathy. [Submitted]
Institution: Karolinska Institutet
Supervisor: Wernerson, Annika
Co-supervisor: Elinder, Carl-Gustaf; Hultenby, Kjell; Bruchfeld, Annette
Issue date: 2017-09-07
Rights:
Publication year: 2017
ISBN: 978-91-7676-785-6
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