Numerous cases of chronic kidney disease of unknown cause have emerged among agricultural workers and other manual laborers in various regions of the world. This article describes the clinical ...presentation and epidemiology of the disease, as well as proposed causes.
Climate Change and the Kidney Johnson, Richard J.; Sánchez-Lozada, Laura G.; Newman, Lee S. ...
Annals of nutrition and metabolism,
01/2019, Volume:
74, Issue:
Suppl 3
Journal Article
Peer reviewed
Open access
The worldwide increase in temperature has resulted in a marked increase in heat waves (heat extremes) that carries a markedly increased risk for morbidity and mortality. The kidney has a unique role ...not only in protecting the host from heat and dehydration but also is an important site of heatassociated disease. Here we review the potential impact of global warming and heat extremes on kidney diseases. High temperatures can result in increased core temperatures, dehydration, and blood hyperosmolality. Heatstroke (both clinical and subclinical whole-body hyperthermia) may have a major role in causing both acute kidney disease, leading to increased risk of acute kidney injury from rhabdomyolysis, or heat-induced inflammatory injury to the kidney. Recurrent heat and dehydration can result in chronic kidney disease (CKD) in animals and theoretically plays a role in epidemics of CKD developing in hot regions of the world where workers are exposed to extreme heat. Heat stress and dehydration also has a role in kidney stone formation, and poor hydration habits may increase the risk for recurrent urinary tract infections. The resultant social and economic consequences include disability and loss of productivity and employment. Given the rise in world temperatures, there is a major need to better understand how heat stress can induce kidney disease, how best to provide adequate hydration, and ways to reduce the negative effects of chronic heat exposure.
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BFBNIB, NMLJ, NUK, PNG, UL, UM, UPUK
Objective
Agricultural workers worldwide exposed to heat stress could be at the risk of kidney injury, which could lead to chronic kidney disease of an unknown origin (CKDu). Hydration has been ...promoted as a key measure to reduce kidney injury. In the presence of a hydration intervention, the incidence of acute kidney injury (AKI) was calculated in a sugarcane worker population in Guatemala and several risk factors were evaluated.
Methods
We measured kidney function at the beginning and end of the work shift at three time points in 517 sugarcane workers. We defined AKI as an increase in serum creatinine of 26.5 µmol/L or 50% or more from the pre-shift value. Associations between AKI and risk factors were examined, including interactions with hydration status.
Results
The prevalence of dehydration post-shift (> 1.020 specific gravity) was 11% in February, 9% in March, and 6% in April. Cumulative incidence of AKI was 53% in February, 54% in March, and 51% in April. AKI was associated with increasing post-shift specific gravity, a dehydration marker, (OR 1.24, 95% CI 1.02–1.52) and with lower electrolyte solution intake (OR 0.94, 95% CI 0.89–0.99).
Conclusions
Dehydration and insufficient electrolyte consumption are risk factors for AKI. However even well-hydrated sugarcane workers routinely experience AKI. While hydration is important and protective, there is a need to understand other contributors to risk of AKI and identify prevention strategies with these workers.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Climate change has implications for human health and productivity. Models suggest that heat extremes affect worker health, reduce labor capacity, and commodity supply. Chronic health conditions are ...on the rise internationally. However there is a paucity of direct empirical evidence relating increasing temperatures to both agricultural worker health and productivity.
We evaluated the relationship between temperature exposure, kidney function, and two measures of productivity-tons of commodity produced and job attrition, of 4,095 Guatemalan sugarcane cutters over a 6-month harvest. We used distributed lag non-linear models to evaluate associations between wet bulb globe temperature (WBGT) and productivity of workers with normal or impaired kidney function. The cumulative effect of exposure to a max WBGT of 34°C was 1.16 tons (95% CI: -2.87, 0.54) less sugarcane cut over the next five days by workers with impaired kidney function, compared to exposure to 29°C. Impaired kidney function was associated with premature workforce attrition. Workers starting the harvest season with impaired kidney function were more than twice as likely to leave employment (HR: 2.92, 95% CI: 1.88, 4.32).
Heat extremes may be associated with loss of agricultural worker productivity and employment, especially among those with impaired kidney function. Agricultural workers who develop health conditions, such as kidney disease, are particularly vulnerable in the face of climate change and increasing heat extremes. The resultant loss of employment and productivity has significant implications for global commodity supplies.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Bacterial biofilms are complex communities of cells that are attached to a surface by an extracellular matrix. Biofilms are an increasing environmental and healthcare issue, causing problems ranging ...from the biofouling of ocean-going vessels, to dental plaque, infections of the urinary tract, and contamination of medical instruments such as catheters. A complete understanding of biofilm formation therefore requires knowledge of the regulatory pathways underpinning its formation so that effective intervention strategies can be determined. The master regulator that determines whether the Gram-positive model organism Bacillus subtilis switches from a free-living, planktonic lifestyle to form a biofilm is called SinR. The activity of SinR, a transcriptional regulator, is controlled by its antagonists, SinI, SlrA, and SlrR. The interaction of these four proteins forms a switch, which determines whether or not SinR can inhibit biofilm formation by its repression of a number of extracellular matrix-associated operons. To determine the thermodynamic and kinetic parameters governing the protein-protein and protein-DNA interactions at the heart of this epigenetic switch, we have analyzed the protein-protein and protein-DNA interactions by isothermal titration calorimetry and surface plasmon resonance. We also present the crystal structure of SinR in complex with DNA, revealing the molecular basis of base-specific DNA recognition by SinR and suggesting that the most effective means of transcriptional control occurs by the looping of promoter DNA. The structural analysis also enables predictions about how SinR activity is controlled by its interaction with its antagonists.
Background: An epigenetic switch regulates biofilm formation.
Results: Sequence-specific DNA binding by SinR has been visualized, and the macromolecular interactions in the epigenetic switch have been analyzed.
Conclusion: DNA binding by SinR requires precise protein-DNA contacts and SinR-induced DNA deformation.
Significance: The macromolecular interactions at the center of biofilm formation have been analyzed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Acute kidney injury (AKI) occurs at high rates among agricultural workers (12-33%) in tropical environments. Because of the remote locations affected, traditional laboratory services are often ...unavailable. In this study we compare point of care (POC) creatinine values to standardized laboratory values, and examine the effect of POC testing on the interpretation of AKI rates under tropical field conditions.
Blood samples were collected from 104 sugarcane workers from two time points in January 2018 as a derivation cohort, and from 105 workers from February to April 2017 as a validation cohort. Finger stick and venipuncture samples were drawn at the end of a worker's shift to measure creatinine. Laboratory samples were tested in Guatemala City, Guatemala, in duplicate using the Jaffe Generation 2 method. An adjustment factor to improve agreement with serum creatinine was statistically derived and validated, and then used to determine impact on observed rates of acute kidney injury based on across shift changes in creatinine.
POC creatinine and serum creatinine measures showed that POC consistently overestimated the creatinine by an average of 22% (95% CI: 19.8%, 24.7%) and the disagreement appeared greater at higher values of serum creatinine. An adjustment factor of 0.7775 was applied, which led to significantly greater agreement between the two measures. Rates of AKI in the two combined groups fell from 72% before adjustment to 57% afterwards.
POC testing under tropical field conditions routinely overestimates creatinine compared to laboratory testing, which leads to overestimation of rates of acute kidney injury. The application of an adjustment factor significantly improved the accuracy of the POC value.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Aminoglycosides are widely used antibiotics with notable side effects, such as nephrotoxicity, vestibulotoxicity, and sensorineural hearing loss (cochleotoxicity). MT‐RNR1 is a gene that encodes the ...12s rRNA subunit and is the mitochondrial homologue of the prokaryotic 16s rRNA. Some MT‐RNR1 variants (i.e., m.1095T>C; m.1494C>T; m.1555A>G) more closely resemble the bacterial 16s rRNA subunit and result in increased risk of aminoglycoside‐induced hearing loss. Use of aminoglycosides should be avoided in individuals with an MT‐RNR1 variant associated with an increased risk of aminoglycoside‐induced hearing loss unless the high risk of permanent hearing loss is outweighed by the severity of infection and safe or effective alternative therapies are not available. We summarize evidence from the literature supporting this association and provide therapeutic recommendations for the use of aminoglycosides based on MT‐RNR1 genotype (updates at https://cpicpgx.org/guidelines/ and www.pharmgkb.org).
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Chronic kidney disease of unknown origin (CKDu) is an epidemic concentrated in agricultural communities in Central and South America, including young, male sugarcane harvesters. The purpose of this ...analysis is to understand early changes in kidney function among a cohort of first-time sugarcane harvesters and to determine risk factors for kidney function decline.
Joint latent class mixed models were used to model sub-population kidney function trajectory over the course of 4 years (2012-2016). Probability weighted logistic regression was used to determine personal health, community, and individual behavior risk factors associated with sub-population assignment. Data analysis occurred in 2019.
Of 181 new workers median age 19 years old (IQR: 4), 39 (22%) were identified as having non-stable kidney function with an annual age-adjusted decline of estimated glomerular filtration rate (eGFR) of -1.0 ml/min per 1.73 m2 (95% CI: -3.4, 1.3). Kidney function (OR: 0.96; 95% CI: 0.93, 0.98), mild hypertension (OR: 5.21; 95% CI: 2.14, 13.94), and having a local home of residence (OR: 7.12; 95% CI: 2.41, 26.02) prior to employment in sugarcane were associated with non-stable eGFR sub-population assignment.
Mild hypertension may be an early indicator of the development of CKDu. A better understanding of preexisting risk factors is needed to determine why individuals are entering the workforce with reduced kidney function and elevated blood pressure and increased risk of renal function decline.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
An epidemic of chronic kidney disease of unknown etiology (Mesoamerican nephropathy) has emerged in hot regions of Central America. We have demonstrated that dehydration associated with recurrent ...heat exposure causes chronic kidney disease in animal models. However, the independent influence of core body temperature on kidney injury has not been explored. In the present study, we tested the hypothesis that kidney injury could be accelerated by increasing body temperature independent of external temperature. Wild-type mice were exposed to heat (39.5°C, 30 min, 2 times daily) with or without the mitochondrial uncoupling agent 2,4-dinitrophenol (DNP) for 10 days. Core temperature, renal function, proteinuria, and renal histological and biochemical analyses were performed. Isolated mitochondria markers of oxidative stress were evaluated from kidney tissue. DNP increased body core temperature in response to heat by 1°C (42 vs. 41°C), which was transient. The mild increase in temperature correlated with worsening albuminuria (
= 0.715,
< 001), renal tubular injury, and interstitial infiltration of monocytes/macrophages. Tubular injury was marked in the outer medulla. This was associated with a reduction in kidney tissue ATP levels (nonheated control: 16.71 ± 1.33 nmol/mg and DNP + heat: 13.08 ± 1.12 nmol/mg,
< 0.01), reduced mitochondria, and evidence for mitochondrial oxidative stress. The results of the present study suggest that kidney injury in heat stress is markedly worsened by increasing core temperature. This is consistent with the hypothesis that clinical and subclinical heat stroke may play a role in Mesoamerican nephropathy.
Natural evolution produced polypeptides that selectively recognize chemical entities and their polymers, ranging from ions to proteins and nucleic acids. Such selective interactions serve as entry ...points to biological signaling and metabolic pathways. The ability to engineer artificial versions of such entry points is a key goal of synthetic biology, bioengineering and bioelectronics. We set out to map the optimal strategy for developing artificial small molecule:protein complexes that function as chemically induced dimerization (CID) systems. Using several starting points, we evolved CID systems controlled by a therapeutic drug methotrexate. Biophysical and structural analysis of methotrexate-controlled CID system reveals the critical role played by drug-induced conformational change in ligand-controlled protein complex assembly. We demonstrate utility of the developed CID by constructing electrochemical biosensors of methotrexate that enable quantification of methotrexate in human serum. Furthermore, using the methotrexate and functionally related biosensor of rapamycin we developed a multiplexed bioelectronic system that can perform repeated measurements of multiple analytes. The presented results open the door for construction of genetically encoded signaling systems for use in bioelectronics and diagnostics, as well as metabolic and signaling network engineering.
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