A Systematic Review of Renal Pathology in Chronic Kidney Disease of Uncertain Etiology

Abstract

Introduction: Despite much research on chronic kidney disease of uncertain etiology (CKDu) in Sri Lanka and the Mesoamerican nephropathy, the etiology and pathogenesis of this disease remains elusive. The pathology has broadly been described as chronic tubulointerstitial nephritis and no specific signature lesions have been identified.Methods: A scoping review was conducted through MEDLINE and Google Scholar databases for peerreviewed publications on biopsy studies related to CKDu -Sri Lanka and Mesoamerican nephropathy to develop a comparative and critical analysis of the renal pathology found in these patients.Results: Thirteen studies met the selection criteria. Interstitial fibrosis was the predominant lesion in all the studies. Tubulointerstitial and glomerular abnormalities showed a more variable distribution. No characteristic histopathological feature was reported other than a proximal tubular lysosomal inclusion body which was claimed to indicate a toxic etiology. Three main pathogenetic mechanisms were postulated: repeated acute insults leading to scarring, low-grade chronic insults leading to non-inflammatory fibrosis, and tubulointerstitial damage in combination with glomerular injury. The main limitations in the interpretation and comparative analysis of these studies were the heterogeneity in case selection and biopsy reporting.Conclusions: Although no characteristic histopathological feature could be found in CKDu-Sri Lanka or Mesoamerican nephropathy, there are noticeable differences between these two groups in the frequency and severity of the glomerular and tubulointerstitial changes which warrant more explorative studies preferably on kidneys in early stages of the disease. Future strategies should ensure that more uniform selection criteria and reporting methods are used.

Metals and Metallothionein Expression in Relation to Progression of Chronic Kidney Disease of Unknown Etiology (CKDu) in Sri Lanka

“…Involvement of the kidneys in metal homeostasis is known for Ni [ 47 ], Fe [ 48 ], Zn [ 49 ], Cu [ 50 ], As, Cd, Pb [ 51 ], Hg [ 52 ], Cs Cr, U [ 53 ], and Al [ 54 ]. It involves adequate filtration and reabsorption from tubular lumen [ 55 ] so that progressive tubulointerstitial damage in CKD/CKDu [ 3 ] should be fundamental to the observed variation. The sizable number of subjects with unaltered metals ( p > 0.05) despite disease progression ( Figure 4 A,B) is intriguing.…”

“…The disease remains enigmatic as medically recognized risk factors of chronic kidney disease [ 1 , 2 ] do not justify its high prevalence in the north-central province of the country. CKDu progresses via tubulointerstitial damage [ 3 ] that culminates in end-stage renal disease (ESRD). In chronic kidney disease (CKD), the damage to tubulointerstitium may be initiated by reactive oxygen species (ROS) generated due to nephrotoxins such as increased metals [ 4 ] and reabsorbed albumin during albuminuria [ 5 ] in tubular cells.…”

Prevalence of CKD of Unknown Etiology and its Potential Risk Factors in a Rural Population in Sri Lanka

“…1 Despite its widespread distribution, the main clinicopathological features of the disease are similar among the different communities. 2 In Sri Lanka, CKDu is prevalent in the north-central region and the most affected communities are involved in paddy farming. The prevalence of the disease in this region range from 6% to 15%.…”

“… 1 Despite its widespread distribution, the main clinicopathological features of the disease are similar among the different communities. 2 …”

Multi-pronged research on endemic chronic kidney disease of unknown etiology in Sri Lanka: a systematic review

“…Comparison of CKDu in Central America (Mesoamerican Nephropathy) and in Sri Lanka suggests morphological and biochemical similarities (Jayasumana et al 2018 ). Pathology can be described as chronic tubulointerstitial nephritis with interstitial fibrosis as the predominant lesion and a variable distribution of tubulointerstitial and glomerular abnormalities (Gunawardena et al 2021 ).…”