Evidence of tubular damage in the very early stage of chronic kidney disease of uncertain etiology in the North Central Province of Sri Lanka: a cross-sectional study

Abstract

Background In the North Central Province of Sri Lanka, chronic kidney disease of uncertain etiology (CKDue) has increased markedly over the past 15-20 years. Methods From around 4,700 patients who were followed up, 106 affected patients who visited two local clinics in the endemic area for CKDue on August 10, 2009 and 10 pedigrees of 10 of these cases with familial clustering of CKDue participated in this study. Urine samples, collected from affected patients (n = 106), unaffected relative controls (n = 81), and Japanese controls (n = 50), were analyzed for two tubular markers: a1-microglobulin and N-acetyl-b-D-glucosaminidase. Urine samples from patients with CKDue stages 1-4 (n = 101) and all the samples from unaffected relatives and Japanese controls were analyzed for urinary cadmium concentration. Results Urinary excretion of a1-microglobulin was elevated even in the earliest stage of CKDue compared with its levels in unaffected relative controls. Urinary excretion of N-acetyl-b-D-glucosaminidase was elevated only in stage 5. In contrast, urinary cadmium excretion was similar in CKDue patients and in the unaffected relative controls, and levels in both these groups were significantly lower than the level in the Japanese controls. All levels were below the threshold level for renal toxicity, indicating the absence of any evidence of cadmium toxicity. Conclusions The present study indicates that renal tubular damage occurs in the very early stage of CKDue and demonstrates the existence of familial clustering,

Escalating chronic kidney diseases of multi-factorial origin in Sri Lanka: causes, solutions, and recommendations

“…The prevalence of CKD due to these two common causes in the NCP is not different from the rest of the country (Wimalawansa, unpublished). Moreover, there is no evidence to suggest that the CKD-mfo is related to any of the commonly identifiable causes, has an immunogenic origin, or has a genetic background [3,5,17]. Nevertheless, in patients with CKD-mfo, especially those who are older than 50 years, hypertension and diabetes are likely to co-exist and may further aggravates the renal failure [5].…”

“…Renal failure can develop secondary to a variety of toxins, including snakebites [23], herbal toxins and chemicals [23], and immunological disorders, such as glomerulonephritis [6,17,23]. Irrespective of the causative factor(s) of CKD-mfo, the renal tubular damage occurs in patients at an early stage of the disease [17]; with time; it causes irreversible renal fibrosis leading to renal failure and premature death [6,17,24].…”

“…Irrespective of the causative factor(s) of CKD-mfo, the renal tubular damage occurs in patients at an early stage of the disease [17]; with time; it causes irreversible renal fibrosis leading to renal failure and premature death [6,17,24]. Once kidneys are fibrosed, the damage is irreversible, so prevention is the only way forward.…”

“…Research indicates that the renal tubular damage occurring in the early stages of CKD is similar to kidney tubular damage caused by many other known nephrotoxins [17]. Whether there is a particular susceptibility or a genetic trait in those who develop this disease is unknown [17], but this appears unlikely.…”

“…Whether there is a particular susceptibility or a genetic trait in those who develop this disease is unknown [17], but this appears unlikely. There are other pitfalls in some of the assumptions made in published reports.…”