Comparing the genetic and environmental architecture of blood count, blood biochemistry and urine biochemistry biological ages with machine learning

While a large number of biological age predictors have been built from blood samples, a blood count-based biological age predictor is lacking, and the genetic and environmental factors associated with blood-measured accelerated aging remain elusive. In the following, we leveraged 31 blood count biomarkers measured from 489,079 blood samples, 28 blood biochemistry biomarkers measured from 245,147 blood samples, and four urine biochemistry biomarkers measured from 158,381 samples to build three distinct biological age predictors by training machine learning models to predict age. Blood biochemistry significantly outperformed blood count and urine biochemistry in terms of age prediction (RMSE: 5.92+-0.02 vs. 7.60+-0.02 years and 7.72+-0.04 years). We performed genome wide association studies [GWASs], and found accelerated blood biochemistry, blood count and urine biochemistry aging to be respectively 26.2+-0.3%, 18.1+-0.2% and 10.5+-0.5% GWAS-heritable. We identified 1,081 single nucleotide polymorphisms [SNPs] associated with accelerated blood biochemistry aging, 2,636 SNPs associated with accelerated blood cells aging and 24 SNPs associated with accelerated urine biochemistry aging. Similarly, we identified biomarkers, clinical phenotypes, diseases, environmental and socioeconomic factors associated with accelerated blood biochemistry, blood cells and urine biochemistry aging.

In Vivo Comparison of the Phenotypic Aspects and Molecular Mechanisms of Two Nephrotoxic Agents, Sodium Fluoride and Uranyl Nitrate

Because of their nephrotoxicity and presence in the environment, uranium (U) and fluoride (F) represent risks to the global population. There is a general lack of knowledge regarding the mechanisms of U and F nephrotoxicity and the underlying molecular pathways. The present study aims to compare the threshold of the appearance of renal impairment and to study apoptosis and inflammation as mechanisms of nephrotoxicity. C57BL/6J male mice were intraperitoneally treated with a single dose of U (0, 2, 4 and 5 mg/kg) or F (0, 2, 5, 7.5 and 10 mg/kg) and euthanized 72 h after. Renal phenotypic characteristics and biological mechanisms were evaluated by urine biochemistry, gene/protein expression, enzyme activity, and (immuno)histological analyses. U and F exposures induced nephrotoxicity in a dose-dependent manner, and the highest concentrations induced severe histopathological alterations as well as increased gene expression and urinary excretion of nephrotoxicity biomarkers. KIM-1 gene expression was induced starting at 2 mg/kg U and 7.5 mg/kg F, and this increase in expression was confirmed through in situ detection of this biomarker of nephrotoxicity. Both treatments induced inflammation as evidenced by cell adhesion molecule expression and in situ levels, whereas caspase 3/7-dependent apoptosis was increased only after U treatment. Overall, a single dose of F or U induced histopathologic evidence of nephrotoxicity renal impairment and inflammation in mice with thresholds under 7.5 mg/kg and 4 mg/kg, respectively.

Toluene Toxicity: A Case Report of Transdermal Exposure Causing Hypokalemic Paralysis

Rationale: Hypokalemia is a common finding. Typically asymptomatic presentations of neuromuscular weakness emerge at levels below 2.5 mmol/L. Causes include gastrointestinal losses, renal losses, or intracellular shift, with gastrointestinal losses and diuretics accounting for the majority. Although the cause is often apparent on clinical assessment, a systematic approach incorporating urine biochemistry can aid in narrowing the differential in obscure cases. Presentation: We describe a case of a previously healthy 27-year-old man who presented with acute ascending paralysis, with an associated severe hypokalemia and metabolic acidosis. There were no apparent causes on clinical assessment. Diagnosis: Based on analysis of urine biochemistry, we concluded that a pathologic kaluresis was present, and given his acidemia and transient pathology, we diagnosed the patient with hypokalemic paralysis secondary to toluene toxicity. Interventions: We provided supportive care and electrolyte repletion for our patient; no specific therapies for toluene were required. Our patient was counseled regarding appropriate protective measures when handling toluene. Outcomes: Complete neurologic recovery and biochemical normalization occurred within 48 hours of presentation with supportive care. He continued to use proper precautions when handling toluene, and experienced no symptom relapse, or further abnormalities on both blood and urine chemistry. Lessons learned: Using this case, we review an algorithmic approach incorporating urine biochemistries to aid in the workup of hypokalemia. We review toluene as a toxicologic entity and highlight its role as a cause of hypokalemia.

Kidney stones

The composition of kidney stones is variable and the predisposing factors multifactorial. Consequently, a detailed evaluation of the patient’s lifestyle, diet, fluid intake, medical history, drug history, urinary tract anatomy, blood, and urine biochemistry and stone composition is required determine predisposing factors for stone formation in an individual patient. Combinatorial subtle variants in biochemistry may act synergistically to increase risk of stone formation/recurrence. Many medications may alter blood and/or urine biochemistry and predispose to stone formation. Corticosteroids increase absorption of calcium from the gut and cause hypercalciuria. Topirimate (for seizures or migraines), sulphasalazine (for rheumatoid arthritis), diuretics containing triamterene, acetazolamide (for myotonia), antacids containing trisilicate, calcium supplements, vitamin D supplements, vitamin C in high doses, indinavir (for HIV), and some herbal medicines (containing ephedrine) all increase stone risk.

Prevention of idiopathic calcium stones

The main principles of idiopathic calcium oxalate stone prevention are to maintain dilute urine through increasing fluid intake and to reduce calcium and oxalate excretion. The influence of various urinary factors on the risk of stone formation has been quantified mathematically. Urine volume and urinary oxalate concentration are most influential on the risk of stone formation, while magnesium concentration contributes a small amount to risk. It is estimated that around 50% of stone formers will form another stone within five years. Some stone formers have frequent recurrences. Most stone formers ask how they can prevent future episodes. Advice can be generic or personalized, and treatment may include changes to diet, fluid intake, and addition of drugs to alter urine biochemistry.

Increased total antioxidant capacity in renal tissue of female BWF1 mice infected with Plasmodium chabaudi

We have investigated the effect of malaria infection on the urine biochemistry and the renal and hepatic levels of total antioxidant capacity (TAC) in female BWF1 lupus mice. A total of 30 female BWF1 lupus mice were divided into three groups as follows: group (I) control group; group (II) lupus mice infected with live Plasmodium. chabaudi; group (III) lupus mice infected with irradiated P. chabaudi. Mice were killed at day 14 post-infection and plasma samples were collected. live P. chabaudi infection was associated with decreased level of glucose in urine (glucosuria), increased urinary level of both ketones (ketonuria) and blood (hematuria). Additionally, live P. chabaudi infection was associated with increased level of TAC in the renal tissue with decreased level of TAC in the hepatic tissue of infected mice. In conclusion, P. chabaudi infection has a direct effect on the urine biochemistry and the renal and hepatic levels of TAC in BWF1 mice.