Morphological and clinical findings in Sri Lankan patients with chronic kidney disease of unknown cause (CKDu): Similarities and differences with Mesoamerican Nephropathy.

Kjell Hultenby,Anneli Ring,Nalin Priyawardane,Sisira Siribaddana,Annika Wernerson,Julia Wijkström,Rajeewa Dassanayake,Carl-Gustaf Elinder,Nimali Godakanda,Channa Jayasumana,Magnus Söderberg

doi:10.1371/journal.pone.0193056

Abstract

In Sri Lanka, an endemic of chronic kidney disease of unknown origin (CKDu) is affecting rural communities. The endemic has similarities with Mesoamerican Nephropathy (MeN) in Central America, however it has not yet been clarified if the endemics are related diagnostic entities. We designed this study of kidney biopsies from patients with CKDu in Sri Lanka to compare with MeN morphology. Eleven patients with CKDu were recruited at the General Hospital, Polonnaruwa, using similar inclusion and exclusion criteria as our previous MeN studies. Inclusion criteria were 20–65 years of age and plasma creatinine 100–220 μmol/L. Exclusion criteria were diabetes mellitus, uncontrolled hypertension and albuminuria >1g/24h. Kidney biopsies, blood and urine samples were collected, and participants answered a questionnaire. Included participants were between 27–61 years of age and had a mean eGFR of 38±14 ml/min/1.73m2. Main findings in the biopsies were chronic glomerular and tubulointerstitial damage with glomerulosclerosis (8–75%), glomerular hypertrophy and mild to moderate tubulointerstitial changes. The morphology was more heterogeneous and interstitial inflammation and vascular changes were more common compared to our previous studies of MeN. In two patients the biopsies showed morphological signs of acute pyelonephritis but urine cultures were negative. Electrolyte disturbances with low levels of serum sodium, potassium, and/or magnesium were common. In the urine, only four patients displayed albuminuria, but many patients exhibited elevated α-1-microglobulin and magnesium levels. This is the first study reporting detailed biochemical and clinical data together with renal morphology, including electron microscopy, from Sri Lankan patients with CKDu. Our data show that there are many similarities in the biochemical and morphological profile of the CKDu endemics in Central America and Sri Lanka, supporting a common etiology. However, there are differences, such as a more mixed morphology, more interstitial inflammation and vascular changes in Sri Lankan patients.

Highlights

Chronic kidney disease (CKD) is a global health problem
In Central America, the chronic kidney disease of unknown origin (CKDu) endemic is called Mesoamerican Nephropathy (MeN), and men working with heavy physical labor in warm areas near the Pacific Ocean often develop the disease [4, 5]
We found a unique morphology with glomerulosclerosis, signs of glomerular ischemia and podocytic changes in combination with mild to moderate tubulointerstitial damage [6, 7]

Summary

Introduction

Chronic kidney disease (CKD) is a global health problem. The leading causes of CKD are diabetes mellitus, hypertension, and glomerulonephritis [1], but chronic kidney disease of unknown cause (CKDu) is an emerging health problem in some low- and middle income countries, including El Salvador, Nicaragua, Egypt, Sri Lanka and India [2]. These endemics of CKDu share some mutual features; they affect rural populations, men are more often affected than women, and the countries have a hot climate. The cause of MeN is not yet fully understood, but work-related heat stress with losses of water and salts is an established risk factor [8]

Methods

Results

Conclusion