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Alexandre Persu

Publications and source records attributed to Alexandre Persu.

17 recordsLinked to original sources
PubMed2024

Multiple urinary peptides are associated with hypertension: a link to molecular pathophysiology.

OBJECTIVES: Hypertension is a common condition worldwide; however, its underlying mechanisms remain largely unknown. This study aimed to identify urinary peptides associated with hypertension to further explore the relevant molecular pathophysiology. METHODS: Peptidome data from 2876 individuals without end-organ damage were retrieved from the Human Urinary Proteome Database, belonging to general population (discovery) or type 2 diabetic (validation) cohorts. Participants were divided based on systolic blood pressure (SBP) and diastolic BP (DBP) into hypertensive (SBP &#x2265;140&#x200a;mmHg and/or DBP &#x2265;90&#x200a;mmHg) and normotensive (SBP <120&#x200a;mmHg and DBP <80&#x200a;mmHg, without antihypertensive treatment) groups. Differences in peptide abundance between the two groups were confirmed using an external cohort ( n &#x200a;=&#x200a;420) of participants without end-organ damage, matched for age, BMI, eGFR, sex, and the presence of diabetes. Furthermore, the association of the peptides with BP as a continuous variable was investigated. The findings were compared with peptide biomarkers of chronic diseases and bioinformatic analyses were conducted to highlight the underlying molecular mechanisms. RESULTS: Between hypertensive and normotensive individuals, 96 (mostly COL1A1 and COL3A1) peptides were found to be significantly different in both the discovery (adjusted) and validation (nominal significance) cohorts, with consistent regulation. Of these, 83 were consistently regulated in the matched cohort. A weak, yet significant, association between their abundance and standardized BP was also observed. CONCLUSION: Hypertension is associated with an altered urinary peptide profile with evident differential regulation of collagen-derived peptides. Peptides related to vascular calcification and sodium regulation were also affected. Whether these modifications reflect the pathophysiology of hypertension and/or early subclinical organ damage requires further investigation.

Humans↗
PubMed2005

Osteomalacia due to chemotherapy-induced Fanconi syndrome in an adult patient.

BACKGROUND: Chemotherapy-induced Fanconi syndrome is a dangerous condition that could lead to severe electrolyte disturbances and rarely to osteomalacia. CASE: A patient treated with ifosfamide for a metastatic cervix squamous-cell carcinoma was admitted for diffuse, symmetric bilateral pain in bones and articulations. The diagnosis work-up revealed that she suffered from osteomalacia due to a chemotherapy-induced Fanconi syndrome. The patient recovered completely with oral calcitriol supplements. CONCLUSIONS: This very rare chemotherapy-complication suggests that detection of potential tubular dysfunction, by regular serum electrolyte monitoring of patients receiving ifosfamide, may be a reasonable approach to diagnose early chemotherapy-induced Fanconi syndrome, even in adults.

Carcinoma, Squamous Cell↗
PubMed2005

Influence of the endothelial nitric oxide synthase gene on conventional and ambulatory blood pressure: sib-pair analysis and haplotype study.

BACKGROUND: Nitric oxide is involved in the regulation of vascular basal tone and blood pressure. Polymorphisms of NOS3, the gene that codes for endothelial nitric oxide synthase, have been associated with essential hypertension. OBJECTIVE: To look for linkage and association of three di-allelic polymorphisms (Glu298Asp, intron 4 VNTR and T-786C) and the intron 13 CA-repeat of NOS3 with blood pressure as a continuous trait. METHODS: Genotyping was performed in 110 dizygotic white twin pairs from Flanders, Belgium. The influence of NOS3 polymorphisms on conventional and ambulatory blood pressure was assessed by sib-pair analysis and haplotype association analysis. RESULTS: Genotype frequencies were similar to those previously reported in white populations. Sib-pair analysis did not show a significant influence of either polymorphism on blood pressure. Haplotype analysis disclosed a significant association between NOS3 haplotypes and daytime ambulatory diastolic (P = 0.02) and systolic (P < 0.0001) blood pressure, the latter remaining significant after multiple testing was taken into account (P = 0.032). The association between daytime ambulatory systolic blood pressure and NOS3 haplotypes was mainly attributable to four haplotypes accounting for 11.9% of all represented haplotypes. CONCLUSION: We show for the first time a highly significant association of ambulatory blood pressure with NOS3 haplotypes in well-characterized white individuals from Flanders. These results pave the way for studies looking for the influence of NOS3 on blood pressure in high-risk subsets such as diabetic or hypertensive patients. They indicate the importance of ambulatory blood pressure and haplotype analysis in revealing the moderate effect of polymorphisms on blood pressure.

Adult↗
PubMed2004

Comparison between siblings and twins supports a role for modifier genes in ADPKD.

BACKGROUND: Autosomal-dominant polycystic kidney disease (ADPKD) is characterized by intrafamilial variability in renal disease progression, which could result from a combination of environmental and genetic factors. Although a role for modifier genes has been evidenced in mouse models, direct evidence in ADPKD patients is lacking. The analysis of variability in affected siblings and monozygotic (MZ) twins would help evaluate the relative contribution of environment and genetic factors on renal disease progression in ADPKD. METHODS: The difference in the age at end-stage renal disease (ESRD) and the intraclass correlation coefficient (ICC) were quantified in a large series of ADPKD siblings from western Europe and compared with the values obtained in a series of MZ ADPKD twins from the same geographic area. RESULTS: Fifty-six sibships (including 129 patients) and nine pairs of MZ twins were included. The difference in the age at ESRD was significantly higher in siblings (6.9 +/- 6.0 years, range 2 months to 23 years) than in MZ twins (2.1 +/- 1.9 years, range 1 month to 6 years; P = 0.02). Furthermore, the intraclass correlation coefficient was significantly lower in siblings than in MZ twins (0.49 vs. 0.92, respectively; P = 0.003). The intrafamilial difference in the age at ESRD was not influenced by gender. CONCLUSION: These data substantiate the existence of a large intrafamilial variability in renal disease progression in ADPKD siblings. The fact that the variability in siblings is in a significant excess of that found in MZ twins strongly suggests that modifier genes account for a significant part of this variability.

Adult↗
PubMed2004

Recent insights in the development of organ damage caused by hypertension.

Recent recommendations for the management of hypertension have stressed the importance of assessing subclinical target organ damage for the evaluation of cardiovascular risk, the choice of antihypertensive treatment and the follow-up of hypertensive patients. In addition to classic hallmarks of target organ damage (left ventricular hypertrophy, renal dysfunction, microalbuminuria), new concepts emerging from basic research and technical progresses have allowed more accurate and earlier detection of target organ damage affecting the heart (plasma BNP, coronary calcifications), the brain (silent lacunar infarcts, advanced deep white matter lesions, microbleedings) and the vasculature. The latter include markers of diffuse atherosclerosis (carotid intima-media thickness), arterial stiffness (pulse wave velocity, augmentation index) and endothelial dysfunction (increased plasma levels of adhesion molecules). Current studies should help to better define the predictive power of these new phenotypes for the occurrence of overt cardio- and cerebrovascular diseases, their reversibility under antihypertensive treatment and the most adapted therapeutic strategy in at-risk patients. Furthermore, early identification of hypertensive patients more likely to develop target organ damage, will be facilitated by a more global evaluation of cardiovascular risk factors, a better use and wider acceptance of ambulatory BP measurement (including determination of nocturnal dip and blood pressure variability) and, maybe, an increased knowledge of the genetic factors underlying susceptibility to target organ damage. Lastly, randomized studies comparing different classes of antihypertensive drugs should help to test the well-known but frequently challenged concept of additional benefits of some antihypertensive drugs "beyond BP" on prevention and reversal of target organ damage.

Antihypertensive Agents↗
PubMed2003

Multiple thoracic paraspinal meningeal cysts in autosomal dominant polycystic kidney disease.

Spinal meningeal cysts have been reported in 3 patients as an extrarenal manifestation of autosomal dominant polycystic kidney disease (ADPKD). The authors report on a fourth patient with ADPKD who was found to harbor 7 thoracic meningeal cysts, appearing as paraspinal masses on plain films. The authors provide a comprehensive radiologic description of this abnormality.

Cysts↗
PubMed2003

Influence of ACE (I/D) and G460W polymorphism of alpha-adducin in autosomal dominant polycystic kidney disease.

BACKGROUND: The deleterious effect of the DD genotype of ACE in autosomal dominant polycystic kidney disease (ADPKD) remains controversial. Small sample size, population admixture and lack of consideration of parameters modulating the effects of ACE genotype, such as gender or alpha-adducin (ADD) genotype, might explain the discrepancy. METHODS: We investigated the effect of ACE (I/D) polymorphism on the age at end-stage renal disease (ESRD) in a homogeneous population of 191 ADPKD patients, according to gender and genotype for the G460W polymorphism of ADD. Cumulative renal survival was assessed in 276 patients from the same families. RESULTS: Though no effect was detected in the whole population, analysis of the male subset (n = 97) showed that patients harbouring the DD genotype of ACE had a 5-year lower mean age at ESRD than DI + II patients [47.8 +/- 1.8 (n = 31) vs 52.8 +/- 1.1 (n = 66), respectively] (P = 0.02). Furthermore, cumulative renal survival was lower in the corresponding pedigrees [47 +/- 1 years, 95% confidence interval (CI) 45-49, vs 51 +/- 1 years, 95% CI 48-54]. The G460W polymorphism of ADD had no effect on the age at ESRD and cumulative renal survival, either alone or in combination with the ACE (I/D) polymorphism. CONCLUSIONS: In this large series of ADPKD patients, we found no effect of the ACE (I/D) polymorphism on the age at ESRD, either alone or in combination with the G460W polymorphism of ADD. However, a deleterious effect of the DD genotype of ACE on renal disease progression was observed in ADPKD males.

Age Distribution↗
PubMed2002

Intrafamilial phenotype variability in nephrogenic diabetes insipidus.

X-Linked nephrogenic diabetes insipidus (NDI), which accounts for 90% of inherited cases of NDI, is caused by mutations in the AVPR2 gene that encodes the arginine vasopressin (AVP) receptor type 2 (V2R). The V2R mediates the antidiuretic action of AVP in principal cells of the collecting duct. To date, only three AVPR2 mutations (P322S, D85N, and G201D) have been associated with a mild NDI phenotype, and intrafamilial phenotype variability has not been reported in affected males. We describe a novel Belgian family with X-linked NDI caused by substitution of a histidine for an arginine at position 137 (R137H) of AVPR2. This mutation has been identified in two brothers and their mother. The R137H mutation results in a failure of V2R to stimulate adenylate cyclase and has been associated consistently with severe NDI and the inability to increase urinary osmolality to greater than plasma osmolality during water deprivation and/or infusion of 1-desamino-8-d-arginine vasopressin. Detailed examination of the two affected brothers showed the typical NDI phenotype in the 45-year-old proband, whereas a milder clinical phenotype associated with significant urinary concentrating ability during water deprivation was documented in the 33-year-old brother. Thus, in this family, the R137H mutation is associated with either a mild or severe NDI phenotype. Mechanisms that might account for these findings include genetic and/or environmental modifiers.

Amino Acid Sequence↗
PubMed2000

CF gene and cystic fibrosis transmembrane conductance regulator expression in autosomal dominant polycystic kidney disease.

Disease-modifying genes might participate in the significant intrafamilial variability of the renal phenotype in autosomal dominant polycystic kidney disease (ADPKD). Cystic fibrosis (CF) transmembrane conductance regulator (CFTR) is a chloride channel that promotes intracystic fluid secretion, and thus cyst progression, in ADPKD. The hypothesis that mutations of the CF gene, which encodes CFTR, might be associated with a milder renal phenotype in ADPKD was tested. A series of 117 unrelated ADPKD probands and 136 unaffected control subjects were screened for the 12 most common mutations and the frequency of the alleles of the intron 8 polymorphic TN: locus of CF. The prevalence of CF mutations was not significantly different in the ADPKD (1.7%, n = 2) and control (3.7%, n = 5) groups. The CF mutation was DeltaF508 in all cases, except for one control subject (1717-1G A). The frequencies of the 5T, 7T, and 9T intron 8 alleles were also similar in the ADPKD and control groups. Two additional patients with ADPKD and the DeltaF508 mutation were detected in the families of the two probands with CF mutations. Kidney volumes and renal function levels were similar for these four patients with ADPKD and DeltaF508 CFTR (heterozygous for three and homozygous for one) and for control patients with ADPKD collected in the University of Colorado Health Sciences Center database. The absence of a renal protective effect of the homozygous DeltaF508 mutation might be related to the lack of a renal phenotype in CF and the variable, tissue-specific expression of DeltaF508 CFTR. Immunohistochemical analysis of a kidney from the patient with ADPKD who was homozygous for the DeltaF508 mutation substantiated that hypothesis, because CFTR expression was detected in 75% of cysts (compared with <50% in control ADPKD kidneys) and at least partly in the apical membrane area of cyst-lining cells. These data do not exclude a potential protective role of some CFTR mutations in ADPKD but suggest that it might be related to the nature of the mutation and renal expression of the mutated CFTR.

Adult↗