Vitamin D: A Bridge between Kidney and Heart.

Chronic kidney disease (CKD) and cardiovascular disease (CVD) are highly prevalent conditions, each significantly contributing to the global burden of morbidity and mortality. CVD and CKD share a great number of common risk factors, such as hypertension, diabetes, obesity, and smoking, among others. Their relationship extends beyond these factors, encompassing intricate interplay between the two systems. Within this complex network of pathophysiological processes, vitamin D has emerged as a potential linchpin, exerting influence over diverse physiological pathways implicated in both CKD and CVD. In recent years, scientific exploration has unveiled a close connection between these two prevalent conditions and vitamin D, a crucial hormone traditionally recognized for its role in bone health. This article aims to provide an extensive review of vitamin D's multifaceted and expanding actions concerning its involvement in CKD and CVD.

Chronic Kidney Disease with Mineral Bone Disorder and Vascular Calcification: An Overview.

Chronic kidney disease (CKD) is a global health issue with a rising prevalence, affecting 697.5 million people worldwide. It imposes a substantial burden, contributing to 35.8 million disability-adjusted life years (DALYs) and 1.2 million deaths in 2017. The mortality rate for CKD has increased by 41.5% between 1990 and 2017, positioning it as a significant cause of global mortality. CKD is associated with diverse health complications, impacting cardiovascular, neurological, nutritional, and endocrine aspects. One prominent complication is CKD-mineral and bone disorder (MBD), a complex condition involving dysregulation of bone turnover, mineralization, and strength, accompanied by soft tissue and vascular calcification. Alterations in mineral metabolism, including calcium, phosphate, parathyroid hormone (PTH), vitamin D, fibroblast growth factor-23 (FGF-23), and Klotho, play pivotal roles in CKD-MBD. These disturbances, observed early in CKD, contribute to the progression of bone disorders and renal osteodystrophy (ROD). Vascular calcification (VC) is a key component of CKD-MBD, accelerated by CKD. The pathophysiology involves complex processes in vascular smooth muscle cells and the formation of calciprotein particles (CPP). VC is closely linked to cardiovascular events and mortality, emphasizing its prognostic significance. Various serum markers and imaging techniques, including lateral plain X-ray, Kauppila Score, Adragao Score, and pulse wave velocity, aid in VC detection. Additionally, pQCT provides valuable information on arterial calcifications, offering an advantage over traditional scoring systems. CKD poses a substantial global health burden, and its complications, including CKD-MBD and VC, significantly contribute to morbidity and mortality. Understanding the intricate relationships between mineral metabolism, bone disorders, and vascular calcification is crucial for effective diagnosis and therapeutic interventions.

Combination of Intranasal Dexmedetomidine and Midazolam for Sedation in Pediatric Magnetic Resonance Imaging: A Retrospective Observational Study.

BACKGROUND: Intranasal dexmedetomidine associated with midazolam has been used for pediatric magnetic resonance imaging studies because immobility is a fundamental requirement for correct execution. Many studies have shown dexmedetomidine to be a good option for non-operating room sedation. However, identifying the optimal dose remains a key challenge, especially for pediatric patients. METHODS: All medical records of 139 pediatric patients who underwent sedation for magnetic resonance imaging studies between September 2021 and November 2022 at the University Hospital of Salerno, Italy, were retrospectively reviewed about success rate and adverse events. Our protocol required dosing 30 minutes before the procedure. Patients weighing up to 40 kg received intranasal dexmedetomidine (3 µg/kg) with intranasal midazolam (0.2 mg/kg). Those weighing more than 40 kg received intranasal dexmedetomidine (2 µg/kg) with midazolam orally (0.3 mg/kg; maximum dose, 15 mg). RESULTS: A total of 139 pediatric patients, with age range between 2 months and 16 years, median (95% confidence interval) of 3 (3-5) years, and weight range between 4 and 70 kg, median (95% confidence interval) of 19 (15-24) kg, were reviewed.The procedure was satisfactorily completed in 93.5% (130 patients) (P < 0.01). Only 9 (6.5%) patients completed the procedure with general anesthesia; there are hot adverse events. CONCLUSIONS: Our experience with association of intranasal dexmedetomidine and midazolam has a high success rate, with high effectiveness and safety.

Diet and Other Modifiable Factors in Long-Term Decline of Kidney Function: Observational and Population-Based Cohort Study.

BACKGROUND: Lower physical activity, lower alcohol intake, higher protein intake, higher sodium intake, and lower potassium intake related to greater kidney function decline over time, according to previous studies. The present study aimed to analyze the cumulative effects of these factors. METHODS: This prospective, observational, population-based cohort study included 3039 adult examinees of the Gubbio study who participated in the baseline exam and 15-year follow-up exam. Kidney function was evaluated as estimated glomerular filtration rate (eGFR). Habitual physical activity in leisure time and habitual alcohol intake were assessed by questionnaires; dietary intakes of protein, sodium, and potassium were assessed by urinary markers. Based on previous reports, each one of the five modifiable factors was scored 0 for the tertile associated with smaller eGFR decline (low risk), 2 for the tertile associated with greater eGFR decline (high risk), and 1 for the intermediate tertile (intermediate risk). A cumulative score was calculated as the sum of the factor-specific scores and used as the main independent variable. RESULTS: The cumulative score ranged from 0 to 10, that is, from low risk for all factors to high risk for all factors (skewness = 0.032, mean ± SD = 5 ± 2). To avoid the bias of low-n analyses, score 0 was re-coded as 1 and score 10 was recoded as 9; after re-coding, the cumulative score ranged from 1 to 9 (skewness = 0.016, mean ± SD = 5 ± 2). The cumulative score related to annualized eGFR change in multi-variable linear regression (slope = -0.027, 95%CI = -0.039/-0.014, p < 0.001); findings were consistent in apparently healthy examinees and other subgroups. De novo incidence of eGFR < 60 mL/min × 1.73 m2 was higher along the cumulative score (p < 0.001). Compared to score 1 (n examinees = 35, adjusted incidence = 2.0%), incidence of low kidney function was 4.5 times higher in score 5 (n examinees = 624, adjusted incidence = 8.9%) and 6.5 times higher in score 9 (n examinees = 86, adjusted incidence = 12.9%). The cumulative score related to incidence of low kidney function in multi-variable logistic regression (odds ratio = 1.19, 95%CI = 1.08/1.32, p < 0.001). CONCLUSIONS: The combination of five modifiable factors predicted large differences in long-term incidence of low kidney function.

Correlates of Calcidiol Deficiency in Adults-Cross-Sectional, Observational, Population-Based Study.

The prevalence, determinants, and clinical significance of vitamin D deficiency in the population are debated. The population-based study investigated the cross-sectional associations of several variables with serum 25-hydroxyvitamin D (calcidiol) measured using standardized calibrators. The study cohort consisted of 979 persons of the Moli-sani study, both sexes, ages ≥35 years. The correlates in the analyses were sex, age, education, local solar irradiance in the month preceding the visit, physical activity, anthropometry, diabetes, kidney function, albuminuria, blood pressure, serum cholesterol, smoking, alcohol intake, calorie intake, dietary vitamin D intake, and vitamin D supplement. The serum calcidiol was log transformed for linear regression because it was positively skewed (skewness = 1.16). The prevalence of calcidiol deficiency defined as serum calcidiol ≤12 ng/mL was 24.5%. In multi-variable regression, older age, lower solar irradiance, lower leisure physical activity, higher waist/hip ratio, higher systolic pressure, higher serum cholesterol, smoking, lower alcohol intake, and no vitamin D supplement were independent correlates of lower serum calcidiol (95% confidence interval of standardized regression coefficient ≠ 0) and of calcidiol deficiency (95% confidence interval of odds ratio > 1). The data indicate that low serum calcidiol in the population could reflect not only sun exposure, age, and vitamin D supplementation but also leisure physical activity, abdominal obesity, systolic hypertension, hypercholesterolemia, smoking, and alcohol intake.

Relation of Alcohol Intake to Kidney Function and Mortality Observational, Population-Based, Cohort Study.

Data are conflicting about the effects of alcohol intake on kidney function. This population-based study investigated associations of alcohol intake with kidney function and mortality. The study cohort included adult participants in Exam-1, Exam-2 (6-year follow-up), and Exam-3 (20-year follow-up) of the Gubbio study. Kidney function was evaluated as estimated glomerular filtration rate (eGFR, CKD-Epi equation, mL/min × 1.73 m2). Daily habitual alcohol intake was assessed by questionnaires. Wine intake accounted for >94% of total alcohol intake at all exams. Alcohol intake significantly tracked over time (R > 0.66, p < 0.001). Alcohol intake distribution was skewed at all exams (skewness > 2) and was divided into four strata for analyses (g/day = 0, 1−24, 25−48, and >48). Strata of alcohol intake differed substantially for lab markers of alcohol intake (p < 0.001). In multivariable regression, strata of alcohol intake related cross-sectionally to eGFR at all exams (Exam-1: B = 1.70, p < 0.001; Exam-2: B = 1.03, p < 0.001; Exam-3: B = 0.55, p = 0.010) and related longitudinally to less negative eGFR change from Exam-1 to Exam-2 (B = 0.133, p = 0.002) and from Exam-2 to Exam-3 (B = 0.065, p = 0.004). In multivariable Cox models, compared to no intake, intakes > 24 g/day were not associated with different mortality while an intake of 1−24 g/day was associated with lower mortality in the whole cohort (HR = 0.77, p = 0.003) and in the subgroup with eGFR < 60 mL/min × 1.73 m2 (HR = 0.69, p = 0.033). These data indicate a positive independent association of alcohol intake with kidney function not due to a mortality-related selection.

Serum uric acid levels threshold for mortality in diabetic individuals: The URic acid Right for heArt Health (URRAH) project.

BACKGROUND AND AIM: The URRAH (URic acid Right for heArt Health) Study has identified cut-off values of serum uric acid (SUA) predictive of total mortality at 4.7 mg/dl, and cardiovascular (CV) mortality at 5.6 mg/dl. Our aim was to validate these SUA thresholds in people with diabetes. METHODS AND RESULTS: The URRAH subpopulation of people with diabetes was studied. All-cause and CV deaths were evaluated at the end of follow-up. A total of 2570 diabetic subjects were studied. During a median follow-up of 107 months, 744 deaths occurred. In the multivariate Cox regression analyses adjusted for several confounders, subjects with SUA ≥5.6 mg/dl had higher risk of total (HR: 1.23, 95%CI: 1.04-1.47) and CV mortality (HR:1.31, 95%CI:1.03-1.66), than those with SUA <5.6 mg/dl. Increased all-cause mortality risk was shown in participants with SUA ≥4.7 mg/dl vs SUA below 4.7 mg/dl, but not statistically significant after adjustment for all confounders. CONCLUSIONS: SUA thresholds previously proposed by the URRAH study group are predictive of total and CV mortality also in people with diabetes. The threshold of 5.6 mg/dl can predict both total and CV mortality, and so is candidate to be a clinical cut-off for the definition of hyperuricemia in patients with diabetes.

Urinary Potassium and Kidney Function Decline in the Population-Observational Study.

Background-Some data suggest favorable effects of a high potassium intake on kidney function. The present population-based study investigated cross-sectional and longitudinal relations of urinary potassium with kidney function. Methods-Study cohort included 2027 Gubbio Study examinees (56.9% women) with age ≥ 18 years at exam-1 and with complete data on selected variables at exam-1 (1983-1985), exam-2 (1989-1992), and exam-3 (2001-2007). Urinary potassium as urinary potassium/creatinine ratio was measured in daytime spot samples at exam-1 and in overnight timed collections at exam-2. Estimated glomerular filtration rate (eGFR) was measured at all exams. Covariates in analyses included demographics, anthropometry, blood pressure, drug treatments, diabetes, smoking, alcohol intake, and urinary markers of dietary sodium and protein. Results-In multivariable regression, urinary potassium/creatinine ratio cross-sectionally related to eGFR neither at exam-1 (standardized coefficient and 95%CI = 0.020 and -0.059/0.019) nor at exam-2 (0.024 and -0.013/0.056). Exam-1 urinary potassium/creatinine ratio related to eGFR change from exam-1 to exam-2 (0.051 and 0.018/0.084). Exam-2 urinary potassium/creatinine ratio related to eGFR change from exam-2 to exam-3 (0.048 and 0.005/0.091). Mean of urinary potassium/creatinine ratio at exam-1 and exam-2 related to eGFR change from exam-1 to exam-3 (0.056 and 0.027/0.087) and to incidence of eGFR < 60 mL/min per 1.73 m2 from exam-1 to exam-3 (odds ratio and 95%CI = 0.78 and 0.61/0.98). Conclusion-In the population, urinary potassium did not relate cross-sectionally to eGFR but related to eGFR decline over time. Data support the existence of favorable effects of potassium intake on ageing-associated decline in kidney function.

Sodium intake and kidney function in the general population: an observational, population-based study.

BACKGROUND: The relationships of sodium intake to kidney function within the population have been poorly investigated and are the objective of the study. METHODS: This observational, population-based, cross-sectional and longitudinal study targeted 4595 adult participants of the Gubbio study with complete data at baseline exam. Of these participants, 3016 participated in the 15-year follow-up (mortality-corrected response rate 78.4%). Baseline measures included sodium:creatinine ratio in timed overnight urine collection, used as an index of sodium intake, together with serum creatinine, sex, age and other variables. Follow-up measures included serum creatinine and other variables. Estimated glomerular filtration rate (eGFR, mL/min/1.73 m2) was calculated using serum creatinine, sex and age and was taken as an index of kidney function. RESULTS: The study cohort was stratified in sex- and age-controlled quintiles of baseline urine sodium:creatinine ratio. A higher quintile associated with higher baseline eGFR (P < 0.001). In multivariable analysis, the odds ratio (OR) of Stage1 kidney function (eGFR ≥90 mL/min/1.73 m2) was 1.98 times higher in Quintile 5 compared with Quintile 1 [95% confidence interval (CI) 1.50-2.59, P < 0.001]. The time from baseline to follow-up was 14.1 ± 2.5 years. Baseline to follow-up, the eGFR change was more negative along quintiles (P < 0.001). In multivariable analysis, the OR in Quintile 5 compared with Quintile 1 was 2.21 for eGFR decline ≥30% (1.18-4.13, P = 0.001) and 1.38 for worsened stage of kidney function (1.05-1.82, P = 0.006). Findings were consistent within subgroups. CONCLUSIONS: Within the general population, an index of higher sodium intake associated cross-sectionally with higher kidney function but longitudinally with greater kidney function decline.

Reduced Kidney Function and Relative Hypocalciuria-Observational, Cross-Sectional, Population-Based Data.

This observational, cross-sectional, epidemiological analysis investigated relationships of kidney function to urine calcium and other variables. The analyses targeted two population-based samples of adults (Gubbio study and Moli-sani study: n = 3508 and 955, respectively). Kidney function was assessed as estimated glomerular filtration rate (eGFR). Calcium/creatinine ratio (Ca/Cr) was used as index of urinary calcium in timed overnight urine under fed condition (Gubbio study), morning urine after overnight fast (Gubbio study), and first-void morning urine (Moli-sani study). Moli-sani study included also data for glomerular filtered calcium load, tubular calcium handling, and serum phosphorus, parathyroid hormone, 1,25-dihydroxyvitamin D, calcium, and 25-hydroxyvitamin D. eGFR positively and independently related to Ca/Cr (p < 0.001). In multivariate analyses, eGFR lower by 10 mL/min × 1.73 m2 related to overnight urine Ca/Cr lower by 14.0 mg/g in men and 17.8 mg/g in women, to morning urine Ca/Cr lower by 9.3 mg/g in men and 11.2 mg/g in women, and to first-void urine Ca/Cr lower by 7.7 mg/g in men and 9.6 mg/g in women (p < 0.001). eGFR independently related to glomerular filtered calcium load (p < 0.001) and did not relate to tubular calcium handling (p ≥ 0.35). In reduced eGFR only (<90 mL/min × 1.73 m2), low urine Ca/Cr independently related to low serum 1,25-dihydroxyvitamin D (p = 0.002) and did not relate to hyperphosphatemia, high serum parathyroid hormone, or hypocalcemia (p ≥ 0.14). Population-based data indicated consistent associations of lower kidney function with lower urine calcium due to reduction in glomerular filtered calcium. In reduced kidney function, relative hypocalciuria associated with higher prevalence of low serum 1,25-dihydroxyvitamin D.

The Psychosocial Burden of HCV Infection and the Impact of Antiviral Therapy on the Quality of Life in Liver and Kidney Transplant Recipients: A Pilot Study.

BACKGROUND: Therapy with direct-acting antivirals (DAA) for HCV is safe and effective in the liver (LT) and kidney transplant (KT) recipients; however, data on the quality of life (QoL) of patients are scanty. This pilot study is aimed at prospectively evaluating the QoL in LT and KT recipients before and after DAA treatment. METHODS: We prospectively enrolled 17 LT and 11 KT recipients with HCV infection starting a sofosbuvir-based antiviral therapy for 12 weeks. All participants before (T0), 12 (T12), and 24 (T24) weeks after the end of the therapy completed the Short Form Health Survey (SF-36) questionnaire, the Zung Self-rating Depression Scale, and State-Trait Anxiety Inventory (STAI-Y1-Y2). RESULTS: At T0, LT and KT patients were similar for gender, age, BMI, smoking habits, marital status, mean liver stiffness values at Fibroscan, and HCV genotype distribution (p > 0.05). There were no significant differences between the 2 groups in STAI-Y1, STAI-Y2, Zung, and SF-36 scores (p > 0.05). At T12, all the participants showed a sustained virological response (SVR). All items of the SF-36 questionnaire improved from the pretreatment to posttreatment period within the LT group, and the 4 domains role-physical, bodily pain, social function, role-emotional, and mental health reached statistical significance (p < 0.05 in all cases). On the contrary, in KT patients, there was no significant improvement in SF-36 mean scores compared to at baseline at T12 and T24. CONCLUSIONS: This pilot study suggested that DAA therapy is associated with a significant improvement of the QoL only in LT recipients. Probably, KT recipients did not consider HCV a "central player" in the course of their disease, and HCV eradication did not significantly impact on their QoL.

Skin Architecture, Kidney Transplantation, and Their Relationship to Basal and Squamous Cell Carcinomas.

BACKGROUND/AIM: Squamous cell carcinoma (SCC) is highly prevalent in kidney transplant patients (KT). It is characterized by the presence of an inflammatory infiltrate. In this study, we examined the presence of similar infiltrates in intact skin, which could be regarded as a precancerous step. PATIENTS AND METHODS: We retrospectively analyzed skin biopsies of 19 non-transplanted patients with a diagnosis of SCC or basal cell carcinoma (BCC) and 17 KT with either SCC or BCC. RESULTS: KT showed increased inflammatory infiltrate in the subepithelial region, compared to non-transplanted patients. The density of basal cell nuclei was also different among the four groups with an interaction effect between tumor type and transplantation. The extent of inflammatory infiltrates did not correlate with the eGFR and proteinuria. CONCLUSION: KT with a non-melanoma skin cancer show increased intact skin inflammatory infiltrate and alterations in the density of the basal cell layer compared to non-transplanted patients.

Kidney Transplant Modifies the Architecture and Microenvironment of Basal Cell Carcinomas.

BACKGROUND/AIMS: Basal cell carcinoma (BCC) is a frequent type of nonmelanoma skin cancer, which shows a greater prevalence in kidney-transplanted (KT) patients than in the general population. The study of this tumor in KT patients may allow us to understand the influence of the tumor inflammatory microenvironment on cancer behavior, and to design new image analysis methods to determine prognosis and apply personalized medicine. The major hypothesis of the present work is that antirejection drugs, by modifying the B-cell/T-cell balance, induce measurable differences in tumoral cell microarchitecture and in the inflammatory microenvironment in KT patients compared to nontransplanted controls. METHODS: In this retrospective study in an Italian cohort including 15 KT patients and 15 control subjects from the general population who developed BCC, we analyzed tissue microarchitecture and inflammatory infiltrates of BCC using state-of-the-art nonlinear image analysis techniques such as fractal dimension and sample entropy of internuclear distances. RESULTS: KT patients showed a nonsignificant trend to a greater number of nuclei in the basal cell layer compared to non-KT controls and subtle changes in the intact skin compared to controls. Similarly, the number of mitoses per unit length was almost doubled in the patients with KT compared to controls. However, when the number of mitotic cells was normalized by the total number of cells in the basal layer (mitotic index), these differences were not significant, although a clear trend was still present. Finally, KT patients showed a nonsignificant trend to an increased -density of inflammatory cells close to the tumoral cell layer. When considering the intact skin, this difference was significant, with a 70% increase in the density of inflammatory cells. CONCLUSION: Data comparing the microarchitecture of BCC in normal subjects and KT patients are scanty, and the present study is the first to use nonlinear image analysis techniques to this aim. The observed differences underscore the relevance of T-cell suppression in cancer behavior. These data suggest that BCC develops in treated patients with specific biological characteristics which should be further analyzed in terms of therapeutic response.

25-Hydroxyvitamin D, 1,25-Dihydroxyvitamin D, and Peripheral Bone Densitometry in Adults with Celiac Disease.

Background: Adults with celiac disease (CeD) show low bone mineral density (BMD) and high fracture risk. CeD guidelines suggest measurements of serum minerals and vitamin D. However, studies on vitamin levels in CeD patients are contradictory. Aim: To investigate in CeD, 25-hydroxy-vitamin D [25(OH)D], 1,25-dihydroxy-vitamin D [1,25(OH)2D], and related analytes and to evaluate their relationships to peripheral BMD as assessed by peripheral quantitative computed tomography (pQCT). Methods: Gluten-free diet (GFD)-treated, and untreated adult CeD patients naïve to vitamin D and calcium supplementation underwent measurements of serum 25(OH)D, 1,25(OH)2D, parathyroid hormone (PTH), total calcium, phosphate, and of radius BMD by pQCT. Results: Complete data were collected in 105 patients for lab tests and 87 patients for BMD. For lab tests, untreated CeD differed from treated CeD for 22.0% lower serum 25(OH)D (p = 0.023), 42.5% higher serum PTH (p < 0.001), and 13.0% higher serum 1,25(OH)2D (p = 0.029) in the presence of similar serum calcium and phosphorus (p > 0.35). For BMD, untreated CeD differed from treated CeD for lower diaphyseal cortical BMD (1133 and 1157 mg/cm3, p = 0.004) but not for distal BMD (total, trabecular, and subcortical, p > 0.13). Independent correlates of diaphyseal cortical BMD were GFD treatment and body mass index (p < 0.05). Conclusions: Data indicated that, compared to CeD patients on a gluten-free diet, untreated adult CeD patients at diagnosis had lower 25(OH)D, higher PTH, and higher 1,25(OH)2D in the absence of difference in serum calcium and phosphorus. 25(OH)D and 1,25(OH)2D, even below the normal range, were not associated with BMD. Our findings do not support the use of vitamin D supplementation for all CeD adults.

Vitamin D Status and Indices of Mineral Homeostasis in the Population: Differences Between 25-Hydroxyvitamin D and 1,25-Dihydroxyvitamin D.

Opinions are conflicting about the epidemiology of vitamin D deficiency. This population-based study investigated cross-sectionally the associations of 25-hydroxyvitamin D (calcidiol) and 1,25-dihydroxyvitamin D (calcitriol) with indices of mineral homeostasis. Study cohort consisted of 979 persons of the Moli-Sani study, both sexes, ages ≥35 years. Data collection included serum calcidiol by different assays, serum calcitriol, serum parathyroid hormone, serum and urine calcium, and phosphorus. Prevalence of mild-to-moderate calcidiol deficiency (10-19 ng/mL) was 36.4% and did not associate with hypocalcemia or hyperparathyroidism. Prevalence of severe calcidiol deficiency (<10 ng/mL) was 16.8% and associated with hyperparathyroidism only (odds ratio = 8.81, 95% confidence interval = 2.4/32.9). Prevalence of calcitriol deficiency (<18 pg/mL) was 3.1% and associated with hypocalcemia (29.1, 7.4/114.5) but not hyperparathyroidism. In ANOVA along concentration strata, lower calcidiol associated with higher parathyroid hormone only (p < 0.001). Lower calcitriol associated with lower serum and urine calcium (p < 0.001) but not with parathyroid hormone. Calcidiol findings were consistent with different calcidiol assays. In the population, mild-to-moderate calcidiol deficiency did not associate with abnormal mineral homeostasis. Severe calcidiol deficiency and calcitriol deficiency associated with different disorders: lower calcidiol associated with hyperparathyroidism whereas lower calcitriol associated with hypocalcemia and low urine calcium.

Saliva for assessing creatinine, uric acid, and potassium in nephropathic patients.

BACKGROUND: Lab tests on saliva could be useful because of low invasivity. Previous reports indicated that creatinine, uric acid, and potassium are measurable in saliva. For these analytes the study investigated methodology of saliva tests and correlations between plasma and saliva levels. METHODS: The study enrolled 15 healthy volunteers for methodological analyses and 42 nephropathic patients for plasma-saliva correlations (35 non-dialysis and 7 dialysis). Saliva was collected by synthetic swap right after venipuncture for blood withdrawal. Blood and saliva, unless otherwise indicated, were collected early in the morning after overnight fast and lab tests were performed in fresh samples by automated biochemistry (standard). Methodological analyses included blind duplicates, different collection mouth sites, day-to-day variability, different collection times, and freezing-thawing effects. Analyses on plasma-saliva correlations included post-dialysis changes. RESULTS: For saliva lab tests of all analytes, blind duplicates, samples from different mouth sites or of different days were not significantly different but were significantly correlated (differences ≤14.4%; R ≥ 0.620, P ≤ 0.01). For all analytes, mid-morning saliva had lower levels than but correlated with standard saliva (differences ≥15.8%; R ≥ 0.728, P ≤ 0.01). Frozen-thawed saliva had lower levels than fresh saliva for uric acid only (- 17.2%, P < 0.001). Frozen-thawed saliva correlated with fresh saliva for all analytes (R ≥ 0.818, P ≤ 0.001). Saliva and plasma levels differed but correlated with plasma for creatinine (R = 0.874, P < 0.001), uric acid (R = 0.821, P < 0.001) and potassium (R = 0.767, P < 0.001). Post-dialysis changes in saliva paralleled post-dialysis changes in plasma. CONCLUSION: Saliva levels of creatinine, uric acid, and potassium are measurable and correlated with their plasma levels. Early morning fasting fresh saliva samples are advisable because later collection times or freezing lower the saliva levels of these analytes.

Dietary Protein, Kidney Function and Mortality: Review of the Evidence from Epidemiological Studies.

The World Health Organization recommends a minimum requirement of 0.8 g/day protein/kg ideal weight. Low protein diets are used against kidney failure progression. Efficacy and safety of these diets are uncertain. This paper reviews epidemiological studies about associations of protein intake with kidney function decline and mortality. Three studies investigated these associations; two reported data on mortality. Protein intake averaged >60 g/day and 1.2 g/day/kg ideal weight. An association of baseline protein intake with long-term kidney function decline was absent in the general population and/or persons with normal kidney function but was significantly positive in persons with below-normal kidney function. Independent of kidney function and other confounders, a J-curve relationship was found between baseline protein intake and mortality due to ≈35% mortality excess for non-cardiovascular disease in the lowest quintile of protein intake, a quintile where protein intake averaged <0.8 g/day/kg ideal weight. Altogether, epidemiological evidence suggests that, in patients with reduced kidney function, protein intakes of ≈0.8 g/d/kg ideal weight could limit kidney function decline without adding non-renal risks. Long-term lower protein intake could increase mortality. In most patients, an intake of ≈0.8 g/day/kg would represent a substantial reduction of habitual intake considering that average intake is largely higher.

Urea and Minerals Monitoring in Space Missions by Spot Samples of Saliva and Urine.

BACKGROUND: Microgravity induces redistribution of body fluids and reductions in muscle and bone mass. These effects correlate with changes in lab test results, including urea and bone minerals. Difficulties with collecting blood and urine during space missions limit the available data. This pilot study investigated metabolic changes during a space mission using untimed spot samples of urine and saliva. Untimed spot urine was used for urinalysis with data normalization per creatinine concentration. Saliva was proven useful as an index of serum urea and phosphorus.METHODS: Two astronauts collected urine and saliva samples 75 ± 5 d before launch (baseline) and 3-5 times during a 6-mo space mission. Samples were collected 3 h after morning breakfast. Urine was collected using a standard NASA device. Saliva was collected using a Salivette™ synthetic swab. Samples were kept frozen using automated biochemistry until lab work-up. Anthropometric data were collected at baseline and after the mission.RESULTS: For astronauts 1 and 2, respectively, total bone mineral density decreased (-1.4% and -0.9%). In-flight changes were as follows: transiently decreased urine urea/creatinine ratio (-32% and -24%), transiently decreased urine phosphorus/creatinine ratio (-52% and -30%), increased urine calcium/creatinine ratio (up to +116% and +27%), and transient increases in saliva urea (up to +48% and +195%) and phosphorus (up to +29% and +46%). The astronaut with greater changes in urine minerals had greater reduction in bone mineral density.DISCUSSION: The results support the hypothesis that untimed samples of urine and saliva are useful for investigation of metabolic changes during space missions. Changes in urine and saliva minerals suggested down-regulation of parathyroid gland activity during the space mission.Bilancio G, Cavallo P, Lombardi C, Guarino E, Cozza V, Giordano F, Cirillo M. Urea and minerals monitoring in space missions by spot samples of saliva and urine. Aerosp Med Hum Perform. 2019; 90(1):43-47.

Salivary levels of phosphorus and urea as indices of their plasma levels in nephropathic patients.

BACKGROUND: Phosphorus and urea are measurable in saliva. Measurements of saliva phosphorus (S-Pho) and saliva urea (S-Urea) could be useful because of low invasivity. Data are limited to saliva tests methodology and to correlations between plasma and saliva compositions. S-Pho and S-Urea were investigated focusing on blind duplicates, differences between collection sites, differences between collection times, freezing-thawing effects, and plasma-saliva correlations. METHODS: Tests were performed using fresh saliva collected by synthetic swap early morning after overnight fast (standard). Methodology was investigated in fifteen healthy volunteers. Plasma-saliva correlations were investigated in thirty nephropathic outpatients. RESULTS: S-Pho and S-Urea in all measurements ranged above detection limits (0.3 mmol/L). In healthy volunteers, S-Pho and S-Urea were similar in duplicates (results for S-Pho and S-Urea: % difference between samples ≤ 4.85%; R between samples ≥ .976, P < .001), in samples from different mouth sites (≤4.24%; R ≥ .887, P < .001), and in samples of different days (≤5.61%; R ≥ .606, P < .01) but, compared to standard, were substantially lower in after-breakfast samples (-28.0% and -21.3%; R ≥ .786, P < .001) and slightly lower in frozen-thawed samples (-12.4% and -5.92%; R ≥ .742, P < .001). In nephropathic patients, S-Pho was higher than but correlated with plasma phosphorus (saliva/plasma ratio 4.80; R = .686, P < .001), whereas S-Urea and plasma urea were similar and correlated with each other (saliva/plasma ratio 0.96; R = .944, P < .001). Post-dialysis changes in S-Pho and S-Urea paralleled post-dialysis changes in plasma phosphorus and urea. CONCLUSION: S-Pho and S-Urea reflect plasma phosphorus and plasma urea. Early morning fasting fresh samples are advisable because collection time and freezing-thawing affect saliva tests.