Early prenatal diagnosis of a recurrent case of short-rib thoracic dysplasia 3 due to compound heterozygosity for variations in the DYNC2H1 gene: an "ultrasound first" approach.

Short-rib thoracic dysplasia 3 with or without polydactyly (OMIM # 613091) represents a clinical spectrum encompassing a heterogeneous group of skeletal dysplasias associated with homozygous or compound heterozygous mutations of DYNC2H1. We describe the case of a couple with two consecutive therapeutic abortions due to a diagnosis of short-rib thoracic dysplasia mutations. In the first pregnancy, the diagnosis has been made at 21 weeks. In the second one, an accurate and early ultrasound examination allowed a diagnosis at 12 weeks. DYNC2H1 mutations were confirmed in both cases. In this report, we underline the importance of an ultrasound evaluation at the end of the first trimester of pregnancy in the detection of early signs of skeletal dysplasias. An early prenatal diagnosis of a short-rib skeletal dysplasia, such as for other severe skeletal dysplasias, is critical to offer a couple the chance of a weighted, informed, and less traumatic decision about the continuation of the pregnancy.

De Novo Inverted Duplication Deletion of 4p in a 14-Week-Old Male Fetus Aborted Due to Multiple Anomalies.

Inverted duplications deletions are rare, complex, and nonrecurrent chromosomal rearrangements associated with a variable phenotype. In this case report, we described the phenotype and genotype of a 14-week-old male fetus, who was aborted after discovery of multiple anomalies (septal cystic hygroma, open abdominal wall, and a nonidentifiable lower limb). At autopsy, fluorescence in situ hybridization and array comparative genomic hybridization identified an inverted duplication with terminal deletion of 4p [46,XY,der(4)del(p16.3)dup(4)(p15.2p16.3)]. Only five genotypically similar cases have been reported, and we hope our case contribution will add meaningful to the body of knowledge.

A ZFHX4 mutation associated with a recognizable neuropsychological and facial phenotype.

Several patients with chromosomal deletions including ZFHX4 gene have been described, whereas point mutations are very rare. This gene encodes for a transcription factor involved in the development of several embryonal processes, including brain differentiation. Patients with 8q21.11 deletions usually show intellectual disability, short stature, peculiar facial features, and severe eye abnormalities. We describe a female patient with mild intellectual disability, autism spectrum disorder, strabismus, ptosis, low-set and prominent ears, high-arched palate, microretrognathia. Clinical Exome Sequencing revealed the presence of a de novo heterozygous variant in ZFHX4. Therefore, we further investigate the different phenotypes of ZFHX4 mutations and 8q21.11 deletions.

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.

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.

Low Protein Intake in the Population: Low Risk of Kidney Function Decline but High Risk of Mortality.

OBJECTIVE: This population-based study investigated low protein intake, mortality, and kidney function decline. DESIGN: Observational longitudinal cohort study. SUBJECTS: Target cohort consisted of 4,679 adults participating in 1988-1992 and 2001-2007 examinations of the Gubbio Study (baseline and follow-up). Data collection included overnight urine urea nitrogen (UUN) and other variables at baseline, serum creatinine at baseline and follow-up, and mortality from baseline to follow-up. Three hundred seventy-two persons were excluded for missing data. UUN in the lowest 20% of the distribution was defined as low and used as index of low protein intake. Estimated glomerular filtration rate (eGFR, mL/minute × 1.73 m2) was used as kidney function index. INTERVENTION: None (observational study). MAIN OUTCOME MEASURE: Mortality and eGFR decline are the main outcome measures, and eGFR decline was defined as eGFR change from baseline to follow-up ≤ mean-1 standard deviation (Z-score ≤ -1). RESULTS: Eight hundred seventy-one deaths occurred over 15.9 ± 4.0 years of observation (417 from cardiovascular disease and 276 from neoplastic disease). Low UUN associated with mortality (hazard ratio, HR = 1.31, 95% confidence interval, CI = 1.12/1.53) due to association with mortality from neoplastic disease (HR = 1.33, 95% CI = 1.02/1.76). Mortality-corrected follow-up response rate was 79.9% (n = 2845). Baseline to follow-up eGFR change was -9.9 ± 10.1, and eGFR decline was found in 454 examinees. Low UUN associated with eGFR decline only in subgroup with baseline eGFR <90 (n = 1441, odds ratio = 0.44, 95% CI = 0.22/0.85). Low baseline eGFR interacted with the association between low UUN and eGFR decline (P = .024). CONCLUSION: Low protein intake predicted higher mortality in the whole population and lower incidence of eGFR decline only in subgroup with reduced kidney function.

Osmotic indices and kidney concentrating activity: population-based data on correlates and prognostic power.

Background: Research data are limited on indices of osmotic equilibrium and of kidney concentrating activity (KCA). This study investigated correlates and prognostic power of these indices in a sample of the general population. Methods: Urine osmolality (U-osm), plasma osmolality (P-osm), plasma creatinine and other variables were measured by the Gubbio Study for the 1988-92 exam (baseline). Plasma creatinine and other variables were re-measured in the 2001-07 exam (follow-up). KCA was assessed as the U-osm/P-osm ratio and kidney function as estimated glomerular filtration rate (eGFR). Results: Baseline data were complete in 4220 adults, of whom 852 died before follow-up and 2795 participated in the follow-up. At baseline, the following independent cross-sectional associations were identified: female sex and higher urine flow with lower values of U-osm, P-osm and U-osm/P-osm ratio (P < 0.01); obesity with higher values of U-osm, P-osm and U-osm/P-osm ratio (P < 0.01); older age and lower eGFR with lower U-osm, lower U-osm/P-osm ratio and higher P-osm (P < 0.05); hypertension and smoking with lower U-osm and lower U-osm/P-osm ratio (P < 0.05) but not with P-osm. From baseline to follow-up, the annualized rate was 1.26% for mortality and -0.74 ± 0.76 mL/min × 1.73 m2 for eGFR change. Mortality was independently predicted by baseline U-osm and baseline U-osm/P-osm ratio (hazard ratio for one higher standard deviation was ≤0.91, 95% confidence interval was ≤0.97, P < 0.01), but not by baseline P-osm. The eGFR change was not independently predicted by baseline values of U-osm, P-osm and U-osm/P-osm ratio (P ≥ 0.4). Conclusions: Sex, age, obesity, eGFR, urine flow, hypertension and smoking independently associated with U-osm and KCA. U-osm and KCA independently predicted mortality, but not kidney function change over time.

Population-based dose-response curve of glomerular filtration rate to dietary protein intake.

BACKGROUND: Kidney function measured as estimated glomerular filtration rate (eGFR) is a risk factor for mortality and severe diseases. Protein intake up-regulates kidney function. The dose-response curve of eGFR over protein intake is unknown. Urinary urea nitrogen is an objective index of protein intake. METHODS: The study cross-sectionally analysed the relation between overnight urinary urea nitrogen ((on)U-ureaN) and eGFR with and without control for other variables in 4106 adults of the Gubbio population. Analyses were done for serum creatinine (S-cr) also to investigate the independency of results from eGFR calculation. RESULTS: Higher (on)U-ureaN associated with higher eGFR, and lower S-cr independently of sex and age (simple and partial correlation coefficients >0.100, P < 0.001). Analyses by (on)U-ureaN decile indicated sigmoid curves of eGFR and S-cr over (on)U-ureaN with trend to flatness in the lowest 20% and the highest 20% of (on)U-ureaN (<5.19 and >10.12 mg/h, respectively). Multi-variable spline regression indicated that the relation of eGFR over (on)U-ureaN was non-significant for (on)U-ureaN <5.19 mg/h (coefficient = +0.27, 95% CI = -0.31/+0.84, P = 0.364), positive for (on)U-ureaN in the range 5.19-10.12 mg/h (coefficients = 1.35-1.64, lower 95% CI ≥ +0.48, P ≤ 0.002), and non-significant for (on)U-ureaN >10.12 mg/h (coefficient = +0.05, 95% CI = -0.06/ +0.16, P = 0.394). eGFR differed by ≈8 mL/min × 1.73 m(2) between the lowest and highest 20% of (on)U-ureaN distribution. CONCLUSIONS: Higher protein intake relates to higher eGFR. The relation is sigmoid with eGFR up-regulation for (on)U-ureaN >5.19 mg/h, a threshold approximately corresponding to the recommended daily allowance for protein intake (0.8 g/day per kg of ideal weight).

Effects of bed-rest on urea and creatinine: correlation with changes in fat-free mass.

BACKGROUND: Bed-rest experiments are designed for investigation on catabolic effects of hypokinetic conditions and/or for microgravity simulation in on-ground aerospace research. Bed-rest effects include a reduction in fat-free mass and muscle mass. Urea and creatinine are catabolites of endogenous protein and of muscular energetic metabolism which are excreted mainly by the kidney. The study investigated on urea, creatinine, and kidney function during bed-rest. METHODS: Twenty healthy young men underwent a 7-day adaptation period (day-6 to day-0) and a 35-day bed-rest experiment (day1 to day35) during normocaloric diet. Urine were collected from day-3 to day0 (baseline) and from day1 to day35. Blood samples and anthropometrical data were collected at day0 (baseline) and bed-rest days 7, 14, 21, 28, and 35. RESULTS: Bed-rest reduced plasma volume, weight, fat-free mass, and muscle mass (P<0.001). During bed-rest there was a transient increase in plasma and urinary urea, a decrease in plasma creatinine, and no change in urinary creatinine. The overall integral of changes from day0 to day35 was on average +101.7 mg/dL for plasma urea (95%CI = +43.4/+159.9), +82.2 g/24 h for urinary urea (95%CI = +55.8/+108.7), -2.5 mg/dL for plasma creatinine (95%CI = -3.1/-1.9). Bed-rest reduced plasma cistatyn C also, which was used as mass-independent marker of glomerular filtration rate (-13.1%, P<0.05). Correlations with final reduction in fat-free mass and muscle mass were significant for the overall integral of changes in urinary urea from day0 to day35 (R = 0.706, P<0.001) and for early changes in urinary urea and plasma urea from day0 to day7 (R = 0.566, P = 0.009 and R = 0.715, P<0.001, respectively). CONCLUSIONS: Study results shows that urea is a marker of catabolic conditions secondary to hypokinetic conditions.

Protein intake and kidney function in the middle-age population: contrast between cross-sectional and longitudinal data.

BACKGROUND: Protein intake is considered a determinant of glomerular filtration rate (GFR). Urinary urea is an objective marker of protein intake. The population-based study investigated, cross-sectionally and longitudinally, the association of protein intake with GFR, indexed by estimated GFR (eGFR). METHODS: Data were collected on overnight urinary urea, serum creatinine (S-cr), eGFR and other variables in 1522 men and women aged 45-64 years who participated in the Gubbio study (baseline). S-Cr, eGFR and other variables were re-assessed in 1144 of the 1425 survivors after 12-year follow-up. RESULTS: At baseline, mean ± SD was 84.0 ± 11.4 mL/min × 1.73 m(2) for eGFR calculated by CKD-Epi equation and 1.34 ± 0.57 g/day per kg of ideal weight for protein intake assessed by measurements of overnight urine excretion of urea nitrogen. Cross-sectional analyses of baseline data indicated a positive correlation of protein intake with eGFR (R = 0.180, P < 0.001). In multi-variable regression, 1 g/day higher protein intake related to 4.7 mL/min × 1.73 m(2) higher eGFR [95% confidence interval (CI) = 3.7/5.7]. At follow-up, mean ± SD of 12-year eGFR change was -11.6 ± 9.0 mL/min × 1.73 m(2). Baseline protein intake correlated with more negative eGFR change (R = -0.251, P < 0.001). In multi-variable regression, 1 g/day higher protein intake related to -4.1 mL/min × 1.73 m(2) more negative eGFR change (95% CI = -5.1/-3.1) and to 1.78 risk for incidence of eGFR < 60 mL/min × 1.73 m(2) (95% CI = 1.15/2.78). CONCLUSIONS: In middle-aged adults, high protein intake is associated cross-sectionally with higher GFR but longitudinally with greater GFR decline over time.

Parallel-group 8-week study on chlorthalidone effects in hypertensives with low kidney function.

Short-term effects of chlorthalidone are unknown in low kidney function. The effects of 8-week treatment with 25-mg chlorthalidone on the top of ongoing treatment were compared between control hypertensives and low kidney function hypertensives as assessed by estimated glomerular filtration rate <60 mL/min×1.73 m(2). Screening period consisted of 2 visits for patient selection and pretreatment laboratory evaluations (baseline). Inclusion criteria were uncontrolled hypertension on nondiuretic antihypertensive treatment. Exclusion criteria were chlorthalidone contraindications, refused consent, treatment with >3 antihypertensive drugs, severe hypertension, severe comorbidities, unreliable estimated glomerular filtration rate. Treatment period consisted of 5 visits (weeks 1, 2, 4, 6, and 8). Post-treatment laboratory evaluations were performed 3 to 4 days before week-8 visit. The 2 groups differed for baseline estimated glomerular filtration rate (low kidney function and control: n=60 and 60; mean, 39 and 76; range, 15-59 and 60-104) but not for sex, age, and baseline blood pressure. Week-8 blood pressure changes were a decrease in both groups (low kidney function and control: systolic pressure, -20 and -23; 95% confidence interval, -22/-18 and -26/-19; diastolic pressure, -9 and -10, -11/-7, and -13/-8) without significant between-group differences. Incidence of adverse events was similar in the 2 groups (15.0% and 16.7%). Baseline estimated glomerular filtration rate did not predict blood pressure changes and adverse events in either groups (P>0.6). In both groups, post-treatment changes were a decrease for estimated glomerular filtration rate and serum potassium, an increase for serum uric acid (P<0.01). Data show that short-term chlorthalidone effects were not reduced in hypertensives with low kidney function.

Serum uric acid and eGFR_CKDEPI differently predict long-term cardiovascular events and all causes of deaths in a residential cohort.

OBJECTIVES: Serum uric acid (SUA) and estimated glomerular filtration rate (eGFR) were separately assessed as risk factors for incident coronary hard (CHDH), cardiovascular disease (CVDH) or all-cause (ALL) deaths but never concomitantly in a residential cohort. MATERIAL AND METHODS: Men and women aged 35-74years, totaling 2888 subjects were followed 13.5-19.5years for incident CVDH, CHDH and ALL deaths. Systematic comparisons among different end-points were based on: age, gender, systolic blood pressure (SBP), total and HDL cholesterol, cigarette consumption, body mass index, blood glucose, SUA, eGFR from the Chronic Kidney Disease Prognosis Consortium (eGFR_CKDEPI) and (eGFR_CKDEPI)(2). RESULTS: Significant (p<0.00001) differences in SUA quintiles were seen for SBP, total and HDL cholesterol, body mass index and eGFR_CKDEPI whereas cigarettes and blood glucose were not statistically different. There were increasingly larger proportions of all events in SUA quintiles (0.05>p<0.0001). Among 4 major continuous variables, SUA was largely accurate (ROC>0.610) to predict all end-points whereas eGFR_CKDEPI was the worse univariate predictor. Multivariately, age, gender, SBP and cigarettes were significant predictors for all end-points. Total cholesterol was a significant predictor only for CHDH events. Blood glucose and SUA were contributors for CVDH events (RR, for 1mg/dl of SUA, 1.09, 95%CI 1.01-1.17), CVD deaths (RR 1.11, 95%CI 1.03-1.20) and ALL deaths (RR 1.08, 95%CI 1.03-1.14) whereas (eGFR_CKDEPI)(2) was for ALL deaths only (RR 1.02, 95%CI 1.00-1.04). CONCLUSION: SUA is a predictor of long-term incidence of cardiovascular events and deaths and all-cause mortality and should be considered for risk predictive purposes and instruments whereas eGFR_CKDEPI only predicts all-cause mortality by a U-shaped relation.

Homocysteinylated albumin promotes increased monocyte-endothelial cell adhesion and up-regulation of MCP1, Hsp60 and ADAM17.

RATIONALE: The cardiovascular risk factor homocysteine is mainly bound to proteins in human plasma, and it has been hypothesized that homocysteinylated proteins are important mediators of the toxic effects of hyperhomocysteinemia. It has been recently demonstrated that homocysteinylated proteins are elevated in hemodialysis patients, a high cardiovascular risk population, and that homocysteinylated albumin shows altered properties. OBJECTIVE: Aim of this work was to investigate the effects of homocysteinylated albumin - the circulating form of this amino acid, utilized at the concentration present in uremia - on monocyte adhesion to a human endothelial cell culture monolayer and the relevant molecular changes induced at both cell levels. METHODS AND RESULTS: Treated endothelial cells showed a significant increase in monocyte adhesion. Endothelial cells showed after treatment a significant, specific and time-dependent increase in ICAM1 and VCAM1. Expression profiling and real time PCR, as well as protein analysis, showed an increase in the expression of genes encoding for chemokines/cytokines regulating the adhesion process and mediators of vascular remodeling (ADAM17, MCP1, and Hsp60). The mature form of ADAM17 was also increased as well as Tnf-α released in the cell medium. At monocyte level, treatment induced up-regulation of ICAM1, MCP1 and its receptor CCR2. CONCLUSIONS: Treatment with homocysteinylated albumin specifically increases monocyte adhesion to endothelial cells through up-regulation of effectors involved in vascular remodeling.

A population-based approach for the definition of chronic kidney disease: the CKD Prognosis Consortium.

INTRODUCTION: The Kidney Disease: Improving Global Outcomes (KDIGO) foundation promoted the establishment of the Chronic Kidney Disease (CKD) Prognosis Consortium to meta-analyze the association of estimated glomerular filtration rate (eGFR) and albuminuria with incidence of various outcomes in samples of general populations from all over the world. METHODS: Variables in meta-analysis included eGFR by the Modification of Diet in Renal Disease (MDRD) Study equation, the urinary albumin to creatinine ratio (uACR) as index of albuminuria, together with proteinuria at dipstick urinalysis and classical markers of cardiovascular risk. Overall, 105,872 participants had uACR measurements, and 1,128,310 participants had dipstick measurements. RESULTS: The association with mortality was continuous over the whole range of uACR/proteinuria and J-shaped for eGFR which was associated with an excess risk for values <75 and ≥120 ml/min per 1.73 m². Results were similar for the association of eGFR or uACR/proteinuria with renal failure. The associations of eGFR and uACR/proteinuria with death or renal failure were independent of each other. Findings were consistent across population samples from North America, Asia, Oceania and Europe, as well as in individuals with age <65 years and individuals with age ≥65 years. CONCLUSIONS: Data support the threshold of 60 ml/min for CKD definition but suggest that eGFR in the range 60-74 ml/min could represent the early stages of CKD. This first set of results of the CKD Prognosis Consortium represents an important step in the evidence-based definition of CKD. Conclusions should be reevaluated with eGFR calculation by equations less biased for normal-high eGFR.

Clinical, cytogenetic and molecular-cytogenetic characterization of a patient with a de novo tandem proximal-intermediate duplication of 16q and review of the literature.

Partial trisomy 16 is rare and most of the reported cases are secondary to chromosome rearrangements resulting in concurrent monosomies or trisomies of a second chromosome. Only a few patients survive the neonatal period and the duplication of the long arm seems to be mainly responsible for the prenatal lethality of the full trisomy 16. The reported patients with a partial 16q trisomy have a wide spectrum of congenital anomalies that include dysmorphic features, central nervous system malformations, failure to thrive, and club feet. The patients with duplications of proximal 16q frequently have short stature, developmental delay, speech delay, learning difficulties, and mild to severe behavioral problems. Here we describe a patient with an inverted de novo tandem duplication of 16q with breakpoints evaluated in detail by molecular-cytogenetic techniques. Main clinical features include postural, motor and speech delay with severe learning difficulties and behavioral problems, obesity, microcephaly, and mild dysmorphic features. In the report we attempt to classify the few reported patients with pure partial duplications of 16q in more narrow and homogeneous groups: proximal, proximal-intermediate, intermediate, and intermediate-distal duplications. Moreover, we emphasize the importance of proper cytogenetic investigation and complete molecular cytogenetic refinement in all cases with a suspected chromosomal anomaly.

Hydrogen sulfide, the third gaseous signaling molecule with cardiovascular properties, is decreased in hemodialysis patients.

Hydrogen sulfide, H(2)S, is the third endogenous gas with cardiovascular properties, after nitric oxide and carbon monoxide. H(2)S is a potent vasorelaxant, and its deficiency is implicated in the pathogenesis of hypertension and atherosclerosis. Cystathionine beta-synthase, cystathionine gamma-lyase, and 3-mercaptopyruvate sulfurtransferase catalyze H(2)S formation. Chronic kidney disease is characterized by high prevalence of hyperhomocysteinemia, hypertension, and high cardiovascular mortality, especially in hemodialysis patients. H(2)S levels are decreased in hemodialysis patients through transcriptional deregulation of genes encoding for the H(2)S-producing enzymes. Potential implications relate to the pathogenesis of the manifestations of the uremic syndrome, such as hypertension and atherosclerosis.