An Investigation Into the Cardiovascular Risk and Aetiology of CKDu in Sri Lanka

Chronic kidney disease (CKD) is one of the leading causes of hospital admission, clinic attendance and mortality in some provinces of Sri Lanka. In central and southern provinces increased incidence is attributed to type-2 diabetes and hypertension; however, this is not the case in North Central Province (NCP) where CKD of unknown aetiology (CKDu) is the commonest diagnosis. A recent World Health Organisation (WHO) investigation concluded that at least 8,000 people have CKDu2.

First recognized in the early nineties, much work has been done to try to characterise the disease however results are conflicting. Most suggest male paddy farmers working in rural areas of the NCP are worst affected, presenting in their fifth decade with end stage renal failure. However, a recent WHO study revealed higher prevalence in females, although more severe renal impairment was more common in men.

Risk factors include inhabiting NCP > five years, inhabiting the 'dry zone', reduced BMI, lower socio-economic class, and exposure to agrochemicals. There has been suggestion of a genetic link although positive family history is limited to one generation, with no evidence of mendelian progression. Epidemiological studies reveal a clustered geographical distribution with areas such as Medawachchiya, Padaviya and Girandurukotte most affected. High prevalence areas encompass a well-developed irrigation system used for agricultural purposes.

Renal biopsies show tubulointerstitial disease with tubular atrophy, interstitial mononuclear cell infiltration, interstitial fibrosis but no immune-complex deposition on immunofluorescence. This supports a toxin-mediated process.

Many aetiologies have been considered including exposure to heavy metals (cadmium, arsenic) and their chelation by herbicides, fluro-aluminium complexes, agricultural pesticides, mycotoxins, and herbal medicines. Selenium deficiency and genetic susceptibility may be predisposing factors. The true aetiology is likely multifactorial.