Alert! The Prevalence Of Unexplained CKD Is Increasing Year By Year.
Apr 24, 2023
Chronic kidney disease of unknown cause (CKDu) emerged in Central America and Sri Lanka in the 1990s. Unlike traditional chronic kidney disease (CKD), patients with CKD do not have hypertension, diabetes, glomerulonephritis, or other common causes of kidney failure/injury. Most CKDu patients are the "bread and breadwinners" of their families, that is, men aged 20 to 60. In addition, CKDu patients often gradually develop renal failure within 5 years after diagnosis, which brings a serious burden to individuals, families, and society. In recent years, epidemiological surveys have found that the prevalence of CKDu is increasing worldwide, and the incidence area is no longer limited to Sri Lanka or Central America and has its presence in Asia, Europe, and Africa.
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In February 2023, Curr Opin Nephrol Hypertens published a literature review on CKDu1. This review summarizes CKDu epidemiological information, clinical manifestations, pathological features, potential pathogenic mechanisms, and prevention and treatment options. According to this information, CKDu may have susceptible populations in the Hainan and Guangdong, and Guangxi regions of my country, which should be paid attention to by doctors.
Epidemiological information
As early as 1970, a report found that some men engaged in agricultural work had a higher incidence of CKD, but it was not taken seriously. Until the middle and late 1990s, nephrologists in Sri Lanka and Central America discovered that the etiology of such CKD patients could not be explained, and named it CKDu. Unlike traditional CKD, CKD patients do not have common causes of kidney disease such as diabetes, hypertension, obesity, glomerulonephritis, kidney stones, renal obstruction, or nephritis.
In Central America, 7.4%-14.1% of agricultural workers suffer from CKDu, most of whom are engaged in sugarcane cultivation, and the prevalence rate can reach 15% in coastal provinces. In Asia, Sri Lanka was the first country to discover CKDu. The prevalence of CKD in this country is as high as 84%, and most of them are CKD patients. In Taiwan, the prevalence of CKDu among agricultural workers aged 15-60 was 2.7%. In addition, the prevalence of CKDu among agricultural workers in Indonesia, Pakistan, and India ranged from 10% to 53.6%.
In the Middle East and Egypt, the prevalence of CKDu is higher, up to 37.2%. It is worth noting that the risk of kidney injury in children in endemic areas is higher than that in non-endemic areas, and most of them manifest as renal tubular injury and mild renal impairment. However, whether this is directly related to CKDu requires more research.
Most CKDu patients are males aged 20-60 years, and the common job is farming. But the correlation between farming type and CKDu was not consistent. In Asia, rice cultivation is most relevant to CKDu, while in Central America it is sugarcane.
Clinical manifestations
CKDu has common clinical manifestations worldwide, including early blood pressure <140/90mmHg, proteinuria in the non-nephrotic range, and no hypertension or diabetes, but CKDu may be combined with abnormal blood pressure and diabetes in the late stage. When CKDu is diagnosed, patients usually have CKD stage 3-4, which may be accompanied by symptoms such as acute fever, vomiting, and headache.
Of note, although patients with advanced CKDu had a higher prevalence of hypertension, they had a lower prevalence of cardiovascular complications. In addition, CKDu is often accompanied by hyperuricemia, hypokalemia, hyper/hyponatremia, and hyperphosphatemia and hypomagnesemia may also occur.
However, there are regional differences in the clinical manifestations of CKDu. For example, CKDu patients in Taiwan are often complicated with moderate hypertension; CKDu patients in Nicaragua are complicated with urinary crystals, dysuria, and even hematuria and leukocyturia; in Thailand, there are also cases of CKDu with kidney stones; in Egypt, CKDu patients often Combined heart disease.
Pathological features
Tubulointerstitial injury is a common feature of renal biopsy in patients with CKDu, but other aspects vary slightly from region to region. For example, the degree of tubulointerstitial scarring and inflammation is higher in CKDu patients in Sri Lanka than in other regions; glomerular damage, including glomerular fibrosis, sclerosis, and death, may occur in CKDu patients in Central America; On biopsy, lysosomes can be found in proximal tubules; in patients from Nicaragua and Sri Lanka, acute interstitial nephritis (AIN) can be found.
Potential pathogenic mechanism
Currently, the pathophysiology of CKDu is unknown, and it is not even clear whether it is the same disease occurring in different geographic locations or different diseases with overlapping features. In Asia, the mechanism of CKDu is mostly related to drinking water and environmental pollution, such as pesticides, fluoride, heavy metals, and silica pollution of drinking water and air.
In Central America, CKDu is mostly associated with dehydration and heat stress. Also, different crops seem to have different effects on CKDu. As mentioned earlier, in Asia, rice cultivation is associated with CKDu, while in Central America it is sugarcane cultivation. In addition, CKDu may also be related to drugs, genes, smoking, and diet.
Potential control options for CKDu
Although the pathogenic mechanism and pathological features of CKDu are not yet clear, four prevention strategies and two treatment strategies have been proposed1-3.
01 Prevention Program
①Reduce the use of pesticides;
②Provide personal protective equipment for farmers to avoid direct contact with pesticides;
③Provide clean water and a cool rest place when farming, so that farmers can replenish water and get rest in time to avoid dehydration and heatstroke/overheating;
④Avoid patients from contacting/taking nephrotoxic substances, such as non-steroidal anti-inflammatory drugs.
02 Treatment plan
① CKDu test results show that reducing uric acid can improve progressive renal insufficiency;
② Renal replacement therapy. Timely renal replacement therapy can help CKD patients who have progressed to renal failure and prolong their survival.
As a largely agricultural country, China, especially Hainan, and Guangdong, has a subtropical climate with hot weather, and there are many areas where rice and sugarcane are grown, and there are many related agricultural workers. Therefore, doctors in our country should pay attention to this and prevent problems before they happen. On the one hand, physical examination should be strengthened to detect CKD and CKD patients in time. On the other hand, the public should be reminded to ensure rest and drinking water while farming to avoid dehydration and heat stroke.
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References:
1. Nast CC. Chronic kidney disease with unknown causes across the global spectrum. Curr Opin Nephrol Hypertens. 2023 May 1;32(3):223-231.
2. Chang KT, Lin HY. Chronic Kidney Disease of Unknown Cause in Agricultural Communities. N Engl J Med. 2019 Aug 15;381(7):688.
3. Mahalingasivam V, Caplin B. Chronic kidney disease of undetermined etiology: tens of thousands of premature deaths, yet too much remains unknown. Nephrol Dial Transplant. 2019 Nov 1;34(11):1839-1841.
