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Chronic kidney disease of unknown aetiology mostly claims young male farmers: Uva study

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  • Finds cause of death to be end-stage renal disease 
  • Recommends urgent interventions to prevent disease progression
BY Ruwan Laknath Jayakody  The main cause of death in chronic kidney disease of unknown aetiology (CKDu) patients in a study that assessed a sample population from the Badulla District in the Uva Province, among whom the majority were young male farmers, was found to be end-stage renal disease (ESRD), with the majority of such patients not having received renal replacement therapy (RRT) prior to their death.  Therefore, the researchers who conducted their study in Girandurukotte called for immediate interventions to improve the prognosis of CKDu patients in rural farming communities through the development of strategies to minimise the progression of CKDu to ESRD.  These findings and recommendations were made in a short communication on the “Mortality pattern of CKDu in Girandurukotte”, authored by T.W. Hettiarachchi, M.A.A. Nayanamali, T. Sudeshika, W.B.N.T. Fernando, Z. Badurdeen, S. Nanayakkara, S. Wijetunge, L. Gunaratne, and N. Nanayakkara, and published in the Ceylon Journal of Science’s 50th Volume’s 3rd Issue on 6 September 2021.  CKDu, as per “The incidence, prevalence and trends of CKD and CKDu in the North Central Province: An analysis of 30,566 patients” by A.V. Ranasinghe, G.W.G.P. Kumara, R.H. Karunarathna, A.P. De Silva, K.G.D. Sachintani, J.M.C.N. Gunawardena, S.K.C.R.K. Kumari, M.S.F. Sarjana, J.S. Chandraguptha, and M.V.C. De Silva, is an emerging public health problem in developing countries. In “Endemic nephropathy around the world”, F.J. Gifford, R.M. Gifford, M. Eddleston and N. Dhaun, note that CKDu is found to be prevalent in discrete geographical locations in certain tropical countries. According to E.A.N.V. Edirisinghe, H. Manthrithilake, H.M.T.G.A. Pitawala, H.A. Dharmagunawardhane, and R.L. Wijayawardane’s “Geochemical and isotopic (members of a family of an element that all have the same number of protons but different numbers of neutrons) evidences from groundwater and surface water for the understanding of natural contamination in CKDu endemic zones in Sri Lanka”, this form of tubulointerstitial nephropathy (inflammation of the area of the kidney, specifically the swelling of the spaces between the kidney tubules) was first recognised in the North Central Region.  Among patients with CKD, mortality is substantially high, as B. Bikbov, C.A. Purcell, A.S. Levey, M. Smith, A. Abdoli, M. Abebe, and M.O. Owolabi noted in “Global, regional, and national burden of CKD, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017”. CKDu, as Hettiarachchi et al. explained, invariably progresses into end-stage renal disease, which is when renal replacement therapy is required. However, patients die of end-stage renal disease, not receiving renal replacement therapy, or from other causes; for instance, as C.E.Y. Delgado, S.P. Dávila, M.M. Jaramillo and B.E.O. Orozco noted in “Stage progression and the need for renal replacement therapy in a renal protection programme in Colombia. A cohort study” noted that during end-stage renal disease, patients have major cardiovascular, metabolic and cognitive disorders, thus leading to high mortality. Therefore, Hettiarachchi et al. pointed out that therapeutic strategies to prevent the progression to end stage renal disease and the availability of renal replacement therapy are vital when it comes to enhancing the survival of CKD patients.  In 2017, CKD resulted in 1.2 million deaths. Bikbov et al. mentioned that mortality of CKD is constantly increasing with CKD being the 12th cause for deaths in 2017. In Sri Lanka, according to the Annual Health Statistics for 2016, CKD was the eighth-leading cause of in hospital mortality, and also one of the leading causes of deaths in certain regions (in the North Central Province, during the course of five years, 6% of such deaths were reported in the first year subsequent to diagnosis, followed by 17.5% in the second year after diagnosis, and 21.4% in the third year after diagnosis). Also, Ranasinghe et al. found that there was a high disease prevalence and mortality centred round paddy fields and irrigation tanks, thus causing an economic burden to the country.  Hence, Hettiarachchi et al. conducted a study in Girandurukotte (total population of 40,000) from 2005-2015, as J.M. Jayasekara, D.M. Dissanayake, S.B. Adhikari and P. Bandara found in the “Geographical distribution of CKDu in the North Central Region” that the area has a high prevalence for CKDu, based on a total population screening conducted in 2005.  The diagnosis of CKDu has been established, after excluding known causes of CKD by clinical, laboratory, ultrasound scans, and if indicated, after histological (tissue) evaluation.  All confirmed patients were logged into a clinic registry and each patient was given a unique reference number. Subsequent referrals from regional clinics were entered into the registry. All patients were followed up on and provided with treatment according to the guidelines of the kidney disease outcomes quality initiative (KDOQI).  All patients who failed to attend the follow up clinics for six consecutive months or more were identified, and the cause of absence was investigated with the support of the public health team, administrative officers, and relatives.  Up to 2015, 2,974 CKD/CKDu patients were identified and registered in the renal clinic. Among them, while 2,409 attended regular follow-ups, 565 (19%) did not attend the follow-up clinics for more than six consecutive months, out of whom, 208 (7%) died, and while there were no records (including those where the data were missing and where there were errors) to identify the cause of death in 55 cases, 153 deaths were analysed through death certificates and/or hospital records of final admission.  The male to female ratio was 1.6 (128):1 (25) and the mean (average) age of the deceased was 58 years (standard deviation 13.01 years) and 56 years (standard deviation 12.78 years) for males and 55 (standard deviation 14.75 years) years for females. The majority of the deceased were farmers (123-80.39%), of whom, 115 (93.49%) were males and 8 (6.5%) were females. Among the females, 60% were housewives. The mean number of years from diagnosis to death was 5.27 years (standard deviation 3.40 years), and 4.97 years (standard deviation 3.34 years) for males and 6.8 years (standard deviation 3.53 years) for females.  Only nine of the deceased (5.88%) had received renal replacement therapy, where six (3.92%) were on hemodialysis (procedure where a dialysis machine and a special filter called an artificial kidney or a dialyser, are used to clean the blood), one (0.65%) was on peritoneal dialysis (a way to remove waste products from the blood when the kidneys cannot adequately do the job), and two (1.31%) had undergone a kidney transplant.  The immediate cause of death had been recorded as end stage renal disease in 144 (94.12%), followed by cardiovascular disease (CVD) in the case of four (2.60%), cancer in two, severe bladder outflow obstruction in one, hypokalaemia (metabolic imbalance characterised by extremely low potassium levels in the blood) in one, and cirrhosis (late-stage liver disease in which healthy liver tissue is replaced with scar tissue and the liver is permanently damaged) in one.  Discussing the issue, Hettiarachchi et al. explained that studying and evaluating the mortality pattern of CKDu is challenging due to the unavailability of a systematic reporting system (no proper mechanism to report deaths to the health system in order to update registries in hospitals as once a patient dies, all health records are made unavailable to the health system) or detailed, regularly updated, centralised database concerning it (medical record keeping in rural regions is not comparable to electronic databases, as patients records are handwritten and in the possession of the patient).  Explaining the findings, Hettiarachchi et al. noted that the majority of the deceased were male farmers at their most productive age. This high death count, as per Ranasinghe et al., reflected the higher prevalence of the disease among males. Also, Hettiarachchi et al. observed that the higher proportion of deaths among farmers may be due to farming being the main occupation in the area or may represent a causal relationship of the disease to farming-related activity. It was also found that both men and women with lower levels of kidney function had substantially reduced life expectancy. In this regard, T.C. Turin, M. Tonelli, B.J. Manns, P. Ravani, S.B. Ahmed and B.R. Hemmelgarn noted in “CKD and life expectancy” that in general, for the most part, women had a longer life expectancy than men across all levels of age. However, Hettiarachchi et al., found that women had a lesser mean age expectancy than men. With regard to the significant point that a majority of the deaths were around the age of 55 years, Hettiarachchi et al. mentioned that it is remarkably lower than the average life expectancy for Sri Lankans, which is 76.81 years.  Owing to limitations in resources, Sri Lanka has limited access to and no universal access to renal replacement therapy based treatments which are both costly and complicated, as per R. Rope, N. Nanayakkara, A. Wazil, S. Dickowita, R. Abeysekera, L. Gunerathne, and A. Saxena in “Expanding continuous ambulatory (outpatient medical care) peritoneal dialysis (CAPD) in low resource settings: A distance learning approach”.  Patients in this particular area had to travel for a minimum of 100 kilometres to get to the nearest dialysis unit in order to receive dialysis where there are, according to Rope et al., several programmes on the establishment of continuous ambulatory peritoneal dialysis and to expand hemodialysis. That said, a majority of the deceased in this study population had not received renal replacement therapy. 
  1. Thompson, M. James, N. Wiebe, B. Hemmelgarn, B. Manns, S. Klarenbach, and M. Tonelli have found in the “Cause of death in patients with reduced kidney function” that deaths from cardiovascular disease or infection are higher while H. Alani, A. Tamimi and N. Tamimi’s “Cardiovascular co-morbidity in CKD: Current knowledge and future research needs” found that cardiovascular diseases (including an increase in heart failure and valvular disease) have been reported as the main cause of death in CKD. 
However, the results of the instant study showed that cardiovascular diseases accounted for only 2.61% of the deaths while the major proportion of deaths were due to end stage renal failure, which Hettiarachchi et al., explained, may be due to the lower prevalence of cardiovascular disease among CKDu patients in comparison to CKD patients as unlike in CKD patients, cardiovascular deaths were not prominent in CKDu patients.

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