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Insufficient hydration is prevalent among free living adults. This study investigated whether hypohydration alters 1) renal functional reserve, 2) the renal hemodynamic response to the exercise pressor reflex, and 3) urine-concentrating ability during oral protein loading. In a block-randomized crossover design, 22 healthy young adults (11 females and 11 males) underwent 24-h fluid deprivation (Hypohydrated) or 24-h normal fluid consumption (Euhydrated). Renal functional reserve was assessed by oral protein loading. Renal hemodynamics during the exercise pressor reflex were assessed via Doppler ultrasound. Urine-concentrating ability was assessed via free water clearance. Creatinine clearance did not differ at 150 min postprotein consumption between conditions [Hypohydrated: 246 mL/min, 95% confidence interval (CI): 212-280; Euhydrated: 231 mL/min, 95% CI: 196-265, P = 0.2691] despite an elevated baseline in Hypohydrated (261 mL/min, 95% CI: 218-303 vs. 143 mL/min, 95% CI: 118-168, P < 0.0001). Renal artery vascular resistance was not different at baseline (P = 0.9290), but increases were attenuated in Hypohydrated versus Euhydrated at the end of handgrip (0.5 mmHg/cm/s, 95% CI: 0.4-0.7 vs. 0.8 mmHg/cm/s 95% CI: 0.6-1.1, P = 0.0203) and end occlusion (0.2 mmHg/cm/s, 95% CI: 0.1-0.3 vs. 0.4 mmHg/cm/s 95% CI: 0.3-0.6, P = 0.0127). There were no differences between conditions in free water clearance at 150 min postprotein (P = 0.3489). These data indicate that hypohydration 1) engages renal functional reserve and attenuates the ability to further increase creatinine clearance, 2) attenuates increases in renal artery vascular resistance to the exercise pressor reflex, and 3) does not further enhance nor impair urine-concentrating ability during oral protein loading. [ABSTRACT FROM AUTHOR]

Both linkage and association studies have been successfully applied to identify disease susceptibility genes with genetic markers such as microsatellites and Single Nucleotide Polymorphisms (SNPs). As one of the traditional family-based studies, the Transmission/Disequilibrium Test (TDT) measures the over-transmission of an allele in a trio from its heterozygous parents to the affected offspring and can be potentially useful to identify genetic determinants for complex disorders. However, there is reduced information when complete trio information is unavailable. In this study, we developed a novel approach to "infer" the transmission of SNPs by combining both the linkage and association data, which uses microsatellite markers from families informative for linkage together with SNP markers from the offspring who are genotyped for both linkage and a Genome-Wide Association Study (GWAS). We generalized the traditional TDT to process these inferred dosage probabilities, which we name as the dosage-TDT (dTDT). For evaluation purpose, we developed a simulation procedure to assess its operating characteristics. We applied the dTDT to the simulated data and documented the power of the dTDT under a number of different realistic scenarios. Finally, we applied our methods to a family study of alcohol dependence (COGA) and performed individual genotyping on complete families for the top signals. One SNP (rs4903712 on chromosome 14) remained significant after correcting for multiple testing Methods developed in this study can be adapted to other platforms and will have widespread applicability in genomic research when case-control GWAS data are collected in families with existing linkage data.

The high prevalence of inadequate hydration (e.g., hypohydration and underhydration) is concerning given that extreme heat increases excess hospitalizations for fluid/electrolyte disorders and acute kidney injury (AKI). Inadequate hydration may also be related to renal and cardiometabolic disease development. This study tested the hypothesis that prolonged mild hypohydration increases the urinary AKI biomarker product of insulin-like growth factor-binding protein 7 and tissue inhibitor of metalloproteinase-2 ([IGFBP7·TIMP-2]) compared with euhydration. In addition, we determined the diagnostic accuracy and optimal cutoffs of hydration assessments for discriminating positive AKI risk ([IGFBP·TIMP-2] >0.3 (ng/mL)2/1,000). In a block-randomized crossover design, 22 healthy young adults (11 females and 11 males) completed 24 h of fluid deprivation (hypohydrated group) or 24 h of normal fluid consumption (euhydrated group) separated by ≥72 h. Urinary [IGFBP7·TIMP-2] and other AKI biomarkers were measured following the 24-h protocols. Diagnostic accuracy was assessed via receiver operating characteristic curve analysis. Urinary [IGFBP7·TIMP-2] [1.9 (95% confidence interval: 1.0–2.8) vs. 0.2 (95% confidence interval: 0.1–0.3) (ng/mL)2/1,000, P = 0.0011] was markedly increased in hypohydrated versus euhydrated groups. Urine osmolality (area under the curve: 0.91, P < 0.0001) and urine specific gravity (area under the curve: 0.89, P < 0.0001) had the highest overall performance for discriminating positive AKI risk. Optimal cutoffs with a positive likelihood ratio of 11.8 for both urine osmolality and specific gravity were 952 mosmol/kgH2O and 1.025 arbitrary units. In conclusion, prolonged mild hypohydration increased urinary [IGFBP7·TIMP-2] in males and females. Urinary [IGFBP7·TIMP-2] corrected to urine concentration was elevated in males only. Urine osmolality and urine specific gravity may have clinical utility for discriminating positive AKI risk following prolonged mild hypohydration. NEW & NOTEWORTHY This study found that prolonged mild hypohydration in healthy young adults increased the Food and Drug Administration approved acute kidney injury (AKI) biomarker urinary insulin-like growth factor-binding protein 7 and tissue inhibitor of metalloproteinase-2 [IGFBP7·TIMP-2]. Urine osmolality and specific gravity demonstrated an excellent ability to discriminate positive AKI risk. These findings emphasize the importance of hydration in protecting renal health and lend early support for hydration assessment as an accessible tool to assess AKI risk. [ABSTRACT FROM AUTHOR]