Denervation rénale endovascu- laire par radiofréquence: perspective d'un traitement prometteur de l'hypertension artérielle [Renal sympathetic denervation: perspective of a promising treatment for hypertension].

The crucial role of the sympathetic nervous system activity in the initiation and maintenance of hypertension was already in mind in the 1920s when surgical options were proposed to severely hypertensive patients. Despite constant evolution of pharmacological treatments, one estimates that 15-30% of hypertensive patients are still not well controlled and present resistant hypertension. The development of a new endovascular catheter used for selective sympathetic renal denervation by radiofrequency offers new perspectives of treatment. Encouraged by the recent results of the first clinical trials in a targeted population, this procedure could be used in some more indications in the future. However, long term morbidity and mortality of this technique are still not known.

Bolus injections of synthetic atrial natriuretic peptide in patients with chronic renal failure or nephrotic syndrome.

The diuretic and natriuretic responses to exogenous synthetic atrial natriuretic peptide (ANP) were evaluated in patients with chronic renal failure (CRF) or nephrotic syndrome (NS). Patients were studied after an oral water load (8 ml/kg in CRF and 20 ml/kg in NS patients). A short intravenous bolus of either a placebo or ANP was administered when urine output was stable. In each group of patients, three doses of ANP were injected at 24 h intervals, i.e., 1.0, 1.5, and 2.0 micrograms/kg in the CRF and 1.0, 1.5, and 3.0 micrograms/kg in the NS group. Blood pressure and heart rate were monitored throughout the study and urinary volume and electrolyte excretion were measured every 20 min up to 3 h after the bolus. An acute and transient fall in blood pressure was observed immediately after the ANP injection. It was more pronounced in CRF than in NS patients. In CRF patients, ANP caused only a slight increase in urinary volume (13.5-44% over baseline) but a significant increase in urinary sodium excretion (45-114% over baseline). In NS patients, significant increases in both urine volume (60-105%) and sodium excretion (149-248%) were also found. In these latter patients, the renal response to ANP appeared to be better preserved. The hemodynamic and renal changes induced by ANP occurred mainly during the first 20 min following the ANP administration, when the peak plasma ANP levels were obtained. However, no clear dose-response effect could be evidenced in either group with the three doses of ANP chosen in this study.

Anti-60-kDa heat shock protein antibodies in fetal serum: a biomarker for unexplained small for gestational age fetuses.

Introduction: Small for gestational age (SGA) is an important problem affecting 10% of pregnancies and is associated with significant perinatal morbidity. In about 80% of cases, a probable etiology or a major risk factor can be identified. But almost 20% of SGA cases are considered unexplained. The 60-kDa heat shock protein (HSP60) is a highly immunogenic protein whose synthesis is greatly upregulated under nonphysiological conditions. Bacterial and human HSP60 share a high degree of sequence homology, and immunity to conserved epitopes may result in development of autoimmunity following a bacterial infection. We hypothesized that unexplained SGA could be the consequence of immune sensitization to human HSP60. Methods: Unexplained SGA fetuses were identified by ultrasound biometry with normal Doppler velocimetry and with no detectable maternal or fetal abnormalities. Fetal sera were obtained by cordocentesis performed for a karyotype analysis in cases of unexplained SGA (study group) or for screening of Rhesus incompatibility (control group). Fetal sera were tested for HSP60 antigen and for IgG and IgM anti-HSP60 by ELISA as well as for other immune and hematological parameters. Results: Maternal parameters were similar between the 12 study cases and the 23 control cases. The mean gestational age at cordocentesis was 29 weeks. IgM anti-HSP60 was detected in 12 cases (100%) and in no controls (p < 0.00017), while IgG anti-HSP60 was detected in 7 cases (58%) and only 1 control (p < 0.001). Three of the 4 cases with the highest IgM antibody levels died. There were no differences in fetal serum levels of HSP60 antigen or other immune and hematological markers between the two groups. Conclusion: Fetuses with unexplained SGA are positive for IgM and IgG antibody to human HSP60 and the specific IgM antibody level is predictive of fetal mortality. Detection of these antibodies indicates that a placental perturbation and a fetal autoimmune reaction to HSP60 are associated with this developmental delay.

Role of the renal circadian timing system in maintaining water and electrolytes homeostasis.

Many basic physiological functions exhibit circadian rhythmicity. These functional rhythms are driven, in part, by the circadian clock, an ubiquitous molecular mechanism allowing cells and tissues to anticipate regular environmental events and to prepare for them. This mechanism has been shown to play a particularly important role in maintaining stability (homeostasis) of internal conditions. Because the homeostatic equilibrium is continuously challenged by environmental changes, the role of the circadian clock is thought to consist in the anticipative adjustment of homeostatic pathways in relation with the 24h environmental cycle. The kidney is the principal organ responsible for the regulation of the composition and volume of extracellular fluids (ECF). Several major parameters of kidney function, including renal plasma flow (RPF), glomerular filtration rate (GFR) and tubular reabsorption and secretion have been shown to exhibit strong circadian oscillations. Recent evidence suggest that the circadian clock can be involved in generation of these rhythms through external circadian time cues (e.g. humoral factors, activity and body temperature rhythms) or, trough the intrinsic renal circadian clock. Here, we discuss the role of renal circadian mechanisms in maintaining homeostasis of water and three major ions, namely, Na(+), K(+) and Cl(-).

Management of transitional-cell carcinoma of the renal pelvis and ureter.

Transitional-cell carcinoma of the renal pelvis or ureter is a relatively rare disease. Several risk factors are smoking, occupational carcinogens, analgesic abuse or Balkan nephropathy. The grade and stage of the disease have the most significant impact on the outcome. The treatment of renal pelvis and ureter tumours is open or laparoscopic surgery varying from conservative to more extensive surgical procedures, i.e. radical nephroureterectomy including removal of the contents of Gerota's fascia with ipsilateral ureter and a cuff of bladder at its distal extent. Most available data are from retrospective studies and surgery is the mainstay of treatment. Chemotherapy and/or radiation therapy are possible adjuvant or primary treatment for selected patients; however, prospective studies are needed to confirm their use.

Urological complications in renal transplantation from cadaveric donor grafts: a retrospective analysis of 20 years.

INTRODUCTION: This study is a retrospective analysis of ureteral complications and their management from a monocenter series of 277 consecutive renal transplantations. MATERIALS AND METHODS: From September 1979 to June 1999, 277 renal transplantations (cadaveric origin) were performed in 241 patients. The ureter from the kidney graft was inserted into the bladder according to the technique of extravesical implantation described by Lich-Gregoir and Campos-Freire. The study analyzed the time of occurrence and the type of complications observed. The different procedures to restore the transplanted urinary tract are presented. RESULTS: Complications occurred in 43/277 renal transplantations (15.5%). Anastomotic urine leakage or ureteral stricture were the most frequent. The time to appearance of these complications was either short (<1 month) or late (>1 month) in a similar number of cases. Most cases were managed surgically: 33/43 cases (76.7%). The most frequent surgical repair was ureterovesical reimplantation (n=13), followed by: ureteroureteral end-to-end anastomosis (native ureter-ureter transplant, n=5); pyeloureteral anastomosis (native ureter-renal pelvis transplant, n=5); simple revision of ureterovesical implantation (n=4); resection and end-to-end anastomosis of the transplant ureter (n=2); calico-vesicostomy (graft-bladder, n=1); implantation according to Boari (n=1); pyelovesicostomy with bipartition of bladder (n=1), and pyeloileocystoplasty with detubularized ileal graft (n=1). No deaths related to any of the urological complications were reported. However, 2 consecutive vesico-renal refluxes led to the loss of the kidney graft in the long-term. CONCLUSION: The rate of complications observed in this retrospective analysis is similar to the experience of other studies, ranging from 2 to 20%. If the classical extravesical ureteral bladder implantation is to remain an attractive technique due to its simplicity, the surgical team at the training center should be aware of all the means to prevent any ureteral complications, such as the choice of another implantation technique and/or insertion of a transient ureteral stent.

Fetal akinesia in metatropic dysplasia: The combined phenotype of chondrodysplasia and neuropathy?

Dominant mutations in the receptor calcium channel gene TRPV4 have been associated with a family of skeletal dysplasias (metatropic dysplasia, pseudo-Morquio type 2, spondylometaphyseal dysplasia, Kozlowski type, brachyolmia, and familial digital arthropathy) as well as with dominantly inherited neuropathies (hereditary motor and sensory neuropathy 2C, scapuloperoneal spinal muscular atrophy, and congenital distal spinal muscular atrophy). While there is phenotypic overlap between the various members of each group, the two groups were considered to be totally separate with the former being strictly a structural skeletal condition and the latter group being confined to the peripheral nervous system. We report here on fetal akinesia as the presenting feature of severe metatropic dysplasia, suggesting that certain TRPV4 mutations can cause both a skeletal and a neuropathic phenotype. Three cases were detected on prenatal ultrasound because of absent movements in the second trimester. Case 4 presented with multiple joint contractures and absent limb movements at birth and was diagnosed with "fetal akinesia syndrome". Post-interruption and post-natal X-rays showed typical features of metatropic dysplasia in all four. Sequencing of the TRPV4 gene confirmed the presence of de novo heterozygous mutations predicting G78W (Case 1), T740I (Cases 2 and 3), and K276E (Case 4). Although some degree of restriction of movements is not uncommon in fetuses with skeletal dysplasia, akinesia as leading sign is unusual and suggests that certain TRPV4 mutations produce both chondrodysplasia and a peripheral neuropathy resulting in a severe "overlap" phenotype.

Molecular clock is involved in predictive circadian adjustment of renal function.

Renal excretion of water and major electrolytes exhibits a significant circadian rhythm. This functional periodicity is believed to result, at least in part, from circadian changes in secretion/reabsorption capacities of the distal nephron and collecting ducts. Here, we studied the molecular mechanisms underlying circadian rhythms in the distal nephron segments, i.e., distal convoluted tubule (DCT) and connecting tubule (CNT) and the cortical collecting duct (CCD). Temporal expression analysis performed on microdissected mouse DCT/CNT or CCD revealed a marked circadian rhythmicity in the expression of a large number of genes crucially involved in various homeostatic functions of the kidney. This analysis also revealed that both DCT/CNT and CCD possess an intrinsic circadian timing system characterized by robust oscillations in the expression of circadian core clock genes (clock, bma11, npas2, per, cry, nr1d1) and clock-controlled Par bZip transcriptional factors dbp, hlf, and tef. The clock knockout mice or mice devoid of dbp/hlf/tef (triple knockout) exhibit significant changes in renal expression of several key regulators of water or sodium balance (vasopressin V2 receptor, aquaporin-2, aquaporin-4, alphaENaC). Functionally, the loss of clock leads to a complex phenotype characterized by partial diabetes insipidus, dysregulation of sodium excretion rhythms, and a significant decrease in blood pressure. Collectively, this study uncovers a major role of molecular clock in renal function.

Place de ta vitamine D, du sevelamer et du cinacalcet dans la prise en charge des patients en insuffisance rénale [Treatment of secondary hyperparathyroidism in renal insufficiency: role of calcitriol, sevelamer and cinacalcet]

Along with the decrease in kidney function arises a secondary hyperparathyroidism, which constitutes one of the most important risk factor for mortality in patients suffering from renal insufficiency. Treating secondary hyperparathyroidism is challenging, as most of the parameters of mineral metabolism are interconnected. We review here the pathophysiology and treatment options of this entity.

Increased Expression of Renal Cyclooxygenase-2 and Neuronal Nitric Oxide Synthase in Hypertensive Cx40-Deficient Mice.

Cx40-deficient mice (Cx40-/-) are hypertensive due to increased renin secretion. We evaluated the renal expression of neuronal nitric oxide synthase (nNOS) and cyclooxygenases COX-1 and COX-2, three macula densa enzymes. The levels of nNOS were increased in kidneys of Cx40-/- mice, as well as in those of wild-type (WT) mice subjected to the two-kidney one-clip model of hypertension. In contrast, the levels of COX-2 expression were only increased in the hypoperfused kidney of Cx40-/- mice. Treatment with indomethacin lowered blood pressure and renin mRNA in Cx40-/- mice without affecting renin levels, indicating that changes in COX-2 do not cause the altered secretion of renin. Suppression of NOS activity by N(G)-nitro-L-arginine methyl ester (L-NAME) decreased renin levels in Cx40-/- animals, indicating that NO regulates renin expression in the absence of Cx40. Treatment with candesartan normalized blood pressure in Cx40-/- mice, and decreased the levels of both COX-2 and nNOS. After a treatment combining candesartan and L-NAME, the blood pressure of Cx40-/- mice was higher than that of WT mice, showing that NO may counterbalance the vasoconstrictor effects of angiotensin II in Cx40-/- mice. These data document that renal COX-2 and nNOS are differentially regulated due to the elevation of renin-dependent blood pressure in mice lacking Cx40.