[Intravesical instillations for inflammatory and sensory chronic bladder diseases: Literature review and guide to clinical practice]. / Instillations endovésicales pour les cystopathies chroniques inflammatoires et douloureuses : revue de la littérature et guide de la pratique clinique.

INTRODUCTION: Inflammatory and sensory chronic bladder diseases have a significant impact on quality of life. These pathologies share alteration of the layer between urine and urothelium, making the use of topical agents appropriate. OBJECTIVES: Review the efficacy and tolerance of intravesical treatments for these pathologies. Give practical guidelines for the use of agents currently available in France. METHOD: A narrative review was performed in March 2021 using PubMed/MEDLINE, Google Scholar and the international guidelines. Pharmaceutical companies and pharmacies were interviewed. RESULTS: Although numerous molecules were tested over the last 5 decades, only dimethylsulfoxyde and glycosaminoglycans are available in France today. Results are promising: response rates are up to 95% and 84% respectively in bladder pain syndrome. In urinary tract infections, glycosaminoglycans could decrease annual number of cystitis by 2.56 (95% confidence interval (CI) -3.86, -1.26; P<0.001) and increase the time to first cystitis recurrence by 130 days (95% CI: 5.84 - 254.26; P=0.04). In radiation cystitis, results could be comparable to hyperbaric oxygen regarding pain and frequency of voiding (-1.31±1.3 visual analogic scale et -1.5±1.4 voiding per day, respectively, at 12 months, P<0.01). However, literature has a low level of evidence. CONCLUSION: Chronic bladder diseases have limited treatment options. Intravesical agents are a good alternative, although their cost is significant and their outcome uncertain.

2021 opinion from the CUROPF on THE efficacy and safety of mid-urethral slings used in women WITH urinary stress incontinence.

OBJECTIVE: To determine the usefulness of mid-urethral slings (MUS) in the surgical management of women presenting with urinary stress incontinence (USI) METHOD: A consensus committee of multidisciplinary experts (CUROPF) was convened and focused on PICO questions concerning the efficacy and safety of MUS surgery compared to other procedures and concerning which approach (retropubic (RP) vs transobturator (TO)) should be proposed as a first-line MUS surgery for specific subpopulations (obese; intrinsic sphincteric deficiency (ISD); elderly) RESULTS: As compared to other procedures (urethral bulking agents, traditional slings and open colposuspension), the MUS procedure should be proposed as the first-line surgical therapy (strong agreement). MUS surgery can be associated with complications and proper pre-operative informed consent is mandatory (strong agreement). Mini-slings (SIS/SIMS) should only be proposed in clinical trials (strong agreement). Both RP and TO approaches may be proposed for the insertion of MUS (strong agreement). However, if the woman is willing to accept a moderate increase in per-operative risk, the RP approach should be preferred (strong agreement) since it is associated with higher very long-term cure rates and as it is possible to completely remove the sling surgically if a severe complication occurs. The RP approach should be used for the insertion of MUS in a woman presenting with ISD (strong agreement). Either the RP or TO approach should be used for the insertion of MUS in an obese woman presenting with USI (strong agreement). In very obese women (BMI ≥35-40kg/m2), weight loss should be preferred prior to MUS surgery and bariatric surgery should be discussed (strong agreement) CONCLUSION: The current Opinion provides an appropriate strategy for both the selection of patients and the best therapeutic approach in women presenting with USI.

[Complications of mid-urethral sling - A review from the Committee for Female Urology and Pelviperineology for the French Association of Urology]. / Complications des bandelettes sous urétrales : une revue de la littérature par le Comité d'urologie et pelvipérinéologie de la femme de l'Association française d'urologie.

INTRODUCTION: Placement of a mid-urethral sling is the gold standard in the surgical management of stress urinary incontinence in women in France. The cure rate of this material is no longer to be demonstrated, but the per- and post-operative complications are currently the subject of a growing controversy not only in Europe but also across the Channel and across the Atlantic, having led to the modification of operative indications. In France, recommendations are also evolving with a stricter framework for indications for surgery by multidisciplinary consultation meeting and an obligation for postoperative follow-up in the short and long term. OBJECTIVES: In this context, CUROPF realized a review of the literature bringing together the available scientific evidence concerning the occurrence of per- and post-operative complications relating to the installation of mid urethral sling. The bibliographic search was carried out using the Medline database and 123 articles were selected. RESULTS: Analysis of the data highlights various complications, depending on the implanted material, the patient and the indication for surgery. The retro-pubic mid urethral sling provides more bladder erosion during surgery (up to 14%), more suprapubic pain (up to 4%) and more acute urinary retention (up to 19,7%) and postoperative dysuria (up to 26%). The trans obturator mid-urethral sling is responsible for more vaginal erosion during the operation (up to 10,9%), more lower limb pain of neurological origin (up to 26,7%). The risk of developing over active bladder is similar in both procedures (up to 33%). But these risks of complications must be balanced by the strong impact of urinary incontinence surgery on the overall quality of life of these women. CONCLUSION: Thus, surgical failure and long term complications exist but should not limit the surgical management of stress urinary incontinence with mid urethral tape. Women should be treated with individualized decision-making process and long-term follow -up is necessary.

[From paediatric urological care to adult urology. Assessment of a transition consultation for adolescents]. / De l'urologie pédiatrique à l'urologie adulte, quelle prise en charge de l'adolescent ? État des lieux d'une consultation de transition en urologie.

To provide an adequate lifelong urological care in the complex period of adolescence, a transition consultation conducted by a paediatric surgeon and an urologist was developed in our institution. As a real rite of passage, it allows the follow-up and the adapted care of urological conditions, sometimes complex, and permits the transition between childhood and the world of grown-ups. We reported our experience at the Children Hospital of our institution (paediatric surgery and urology departments). During a 6 months period (January-July 2015), forty-five young adults with a mean age of 17.8±3.6 years were seen in transition consultation. Eight patients had neurogenic voiding disorders (4 spina bifida, 1 multiple sclerosis, 1 mitochondrial encephalopathy, 1 metachromic leucodystrophy, 1 paraplegia), 9 patients had idiopathic voiding disorders, 1 patient had a non obstructive malformative uropathy; and 30 patients had surgery during infancy and childhood: hypospadias in 17 young men and malformative uropathy in 13 patients. This consultation occurred within 4.6±4.5 years after the last consultation with paediatric surgeon. For 6 patients, the transition consultation was the first for the urological problem. After this consultation, 8 patients stayed in paediatric surgery and 37 patients were referred to adult urologist. Among those 8 patients: 2 patients had cognitive and psychiatric disorders; 4 patients refused to be transferred to adult unit; 2 patients wanted to come back at transition consultation. Among the 37 patients transferred in adult urological care: 6 patients had urological surgery, and one patient was referred to a sexology consultation. The remaining 30 patients have initiated long-term monitoring. All reconvened patients came back at the follow-up visit (at least 12 months follow-up). A 16-year-old patient (spina bifida with polymalformative syndrome) developed a depressive syndrome at the end of the consultation, in the motive of an awareness of the definitive nature of his handicap and the need of medical follow-up throughout his life. Transition consultation makes easier the passage from paediatric care to adult urological care. It allows a smooth change of interlocutors, facilitates subsequent care and improves compliance to medical follow-up. It requires a good collaboration between paediatric and adult care units. Transition responds to an increasing request of adolescents, families, and medical teams, since care rupture during adolescence can have functional and psychological consequences. LEVEL OF PROOF: 4.

[Long-term outcomes after hypospadias surgery: Sexual reported outcomes and quality of life in adulthood]. / Vie sexuelle des jeunes adultes opérés dans l'enfance d'un hypospadias postérieur.

OBJECTIVE: To evaluate outcomes and long-term sexual quality of life after hypospadias surgery. Seventeen-years-old patients operated for a posterior hypospadias in childhood were included in a transversal study. PATIENTS AND METHODS: Fifteen patients, among the forty children treated since 1997, accepted to participate. These young men (mean age at the first surgery was 27.9±20months) were clinically reviewed and responded to questionnaires (EUROQOL 5, IIEF15 and non-validated questionnaire). This study arises about 8.4±5years after the last visit in paediatric department. RESULTS: Mean study age was 21.2±4.7years. One third of patients thought that global quality of life was distorted. Although 33% of the patients had erectile dysfunction, 80% were satisfied with their sexual quality of life. The most important complains were relative to the penile appearance. Number of procedures was not predictive of patient's satisfaction about penile function and appearance. Thirty-three percents of the patients would have been satisfied to have psychological and medical support. They would be interested in having contact with patients who suffered from the same congenital abnormality. CONCLUSION: These patients had functional and esthetical disturbances. This visit leads to a specific visit in 20% cases. In this study, medical follow-up does not seem to be counselling and had to be adapted. Adequate follow-up transition between paediatric and adult departments especially during adolescence seems to be necessary.

[Tibial nerve transcutaneous stimulation for refractory idiopathic overactive bladder in children and adolescents]. / Stimulation transcutanée du nerf tibial dans le traitement des hyperactivités vésicales réfractaires de l'enfant et de l'adolescent.

INTRODUCTION: The purpose of this study was to evaluate safety and tolerability of transcutaneous tibial nerve stimulation (TENS) in patients under 15years of age with refractory overactive bladder. MATERIALS AND METHODS: A retrospective analysis was conducted on outcomes of TENS (1daily 20-minute session, 10Hz) in patients with refractory overactive bladder, excluding patients with neurogenic bladder. Treatment efficacy was evaluated on symptomatic improvement and voiding schedule. Healing was defined as following: no recurrence of urinary tract infection, normal urodynamic voiding parameters, no nighttime continence disorder, normal uroflowmetry. RESULTS: Nineteen consecutive patients with refractory overactive bladder were treated from November 2010 to March 2012 (11girls, 8boys, age 12.1±2.7 years). Three patients reported only daytime voiding disorders, the others reported daytime and nighttime voiding disorders. Ten patients reported febrile urinary tract infection (1 boy, 9 girls). The average length of treatment was 6 months. Two patients were lost to follow-up. Thirteen patients had only tibial TENS; 3 patients had tibial TENS and trospium chloride or desmopressin. At 1-month assessment, 16 patients out of 17 (94%) reported symptomatic improvement. At the end of treatment, 12 patients out of 17 (70%) met healing criteria (5 boys, 7girls), without relapse within 9 months. Three boys (18%) had partial improvement (no daytime wetting, but increased daytime frequency). No patient reported side effects. CONCLUSION: Tibial TENS is a safe, non invasive and effective treatment in refractory overactive bladder in children. The success rate is 70%, with no side effect and no relapse at the end of the treatment in our study.

[Testicular torsion in children: Factors influencing delayed treatment and orchiectomy rate]. / Torsion du cordon spermatique chez l'enfant : impact du mode de consultation sur le délai de prise en charge et le taux d'orchidectomie.

INTRODUCTION: Acute scrotal pain is a true surgical emergency as patients presenting with acute scrotal pain may suffer from spermatic cord torsion and gonadal loss. We assessed whether the type of consultation (first consultation in our center or secondary transfer from a peripheral hospital or primary care practice), distance from home to hospital, and duration of pain had an impact on the orchiectomy rate. PATIENTS AND METHODS: We retrospectively reviewed the medical records of all patients under 15years of age suffering from acute scrotal pain who had surgical exploration between January 2007 and January 2010 in our center. Patient demographics, transfer status, time to consultation in our center, time to surgery, operative findings and clinical outcome were reviewed. RESULTS: Of the 76 patients with acute scrotal pain in whom surgical exploration was performed, 59 had acute spermatic cord torsion, 16 had torsion of the testicular appendage, and 1 had orchitis. In patients with acute spermatic cord torsion, the median age was 13 years (range: 0.18-14.97). In patients with acute spermatic cord torsion, 32 came straight to our center (direct admission group, 54.2%), and 27 (45.8%) came after a prior consultation out of side the center (transfer group). The median journey was 19km (range: 2.5-113) in the direct admission group and 44km (range: 2.5-393) in the transfer group (P=0.0072). The median time between pain onset and consultation at our center was 4.3h (range: 0.5-48) in the direct admission group, and 11h (range: 2-48) in the transfer group (P=0.6139). The median time between admission at our center and surgery was 2.5h, with no difference between the 2 groups (P=0.8789). The orchiectomy rate was 25% in the direct admission group and 14.8% in the transfer group (P=0.5177). In children who underwent orchiectomy, the duration of pain was consistently over 6h. The duration of pain was greater in patients with orchiectomy (12h [range: 1-72]) than in patients without orchiectomy (12h [range: 6-48]; P=0.0001). CONCLUSION: In this study, the orchiectomy rate depended on the duration of pain but not on transfer status. Acute scrotal pain must lead to surgical exploration as soon as possible, requiring close collaboration between peripheral hospitals, primary care physicians, and referral centers.

[External sphincterotomy using bipolar vaporisation in saline. First results]. / Incontinentation par vaporisation bipolaire du sphincter externe de l'urèthre. Premiers résultats.

OBJECTIVES: The aim of this study was to assess the feasibility, efficacy and tolerance of external urethral sphincter vaporization in saline for treating detrusor-sphincter dyssynergia. MATERIAL: Between 2009 and 2011 a monocentric prospective study of ten men mean age 58±9 years with neurogenic detrusor-sphincter dyssynergia was carried out. Preoperative evaluation included kidney ultrasound scan, 24-hour creatinine clearance, urodynamics, retrograde and voiding urethrocystography and an at least 6 months temporary stent sphincterotomy. Postoperative assessment was composed of an ultrasound scan post-void residual volume measurement when the urethral catheter were removed and 1 year after the procedure, a retrograde and voiding urethrocystography at 3 months and a flexible cystoscopy at 1 year. RESULTS: At the catheter removal, eight patients emptied their bladder at completion, a supra-pubic catheter was temporary left in one case and a patient had a permanent urinary retention. For a mean follow-up of 22±11 months, eight patients emptied their bladder at completion and two had a complete urinary retention related to a detrusor underactivity. An orchitis occurred in one case 1 month after the procedure and an urethral stricture in four cases in 12.75±5.68 months on average. CONCLUSION: External urethral sphincter vaporisation saline was feasible and efficient for treating detrusor-sphincter dyssynergia but was associated with a high risk of urethral stricture.

Myosin II heavy chain isoforms are phosphorylated in an EGF-dependent manner: involvement of protein kinase C.

To explore the involvement and regulation of the nonmuscle myosin II heavy chains isoforms, MHC-A and MHC-B in the chemotaxis of metastatic tumor cells, we analyzed the changes in phosphorylation and cellular localization of these isoforms upon stimulation of prostate tumor cells with epidermal growth factor (EGF). EGF stimulation of prostate tumor cells resulted in transient increases in MHC-A and MHC-B phosphorylation and subcellular localization with quite different kinetics. Furthermore, the kinetics of subcellular localization correlated with the in vivo kinetics of MHC-B phosphorylation but not of MHC-A phosphorylation, suggesting different modes of regulation for these myosin II isoforms. We further showed that protein kinase C (PKC) is involved in the EGF-dependent phosphorylation of MHC-A and MHC-B. To our knowledge, this is the first report demonstrating that MHC phosphorylation might regulate its subcellular localization and that the EGF signal is transmitted to MHC-A and MHC-B via PKC. The correlation between MHC-B phosphorylation and localization in response to EGF stimulation might suggest that MHC-B is the myosin II isoform that is involved in chemotaxis.

Longitudinal analysis of growth over the first 3 years of life in Turner's syndrome.

OBJECTIVE: To evaluate longitudinal growth in Turner's syndrome (TS) over the first 3 years of life. METHODS: Growth of 47 patients with TS was compared with that of 40 age-matched control girls by using an analysis according to the Infancy-Childhood-Puberty and bi-exponential models. RESULTS: A mean of 1.2 SDs were lost before birth and a total of 3.0 SDs were lost by age 3 years. According to the Infancy-Childhood-Puberty model, intrauterine growth retardation contributed -1.24 SDs, a 5-month delay in childhood growth spurt contributed -0.96 SDs, and slow childhood growth contributed an additional -0.8 SDs by age 3 years. The bi-exponential analysis disclosed a quasi-linear first exponent and a confining second exponent, which merged at age 18 months in control subjects and 24 months in patients with TS. The first exponent confers an average annual growth rate of 8.4 cm/y in control subjects and 6.7 cm/y in patients with TS. CONCLUSIONS: Intrauterine growth retardation and the initial 3 years of life contribute most of the deficit in the final height of patients with TS. These data provide a reference of standards for longitudinal growth in patients with TS at age 3 months to 3 years.

Infants with a thumb-in-fist posture.

OBJECTIVE: In early infancy the infant's thumb is not infrequently enclosed within the palm, ie, thumb-in-fist (TIF). This posture has received scant attention in the neurodevelopmental literature. Its prevalence, resolution, and clinical associations were investigated in this study. METHODOLOGY: Two hundred sequentially born, apparently healthy full-term newborn infants comprised the cohort. The whole study group was followed up until the disappearance of the TIF occurred. In the first 150 of the cohort, additional data on development and the neurological status were obtained at 12 months of life. RESULTS: In 125 infants (62.5%) of the total cohort, a TIF was noted. The mean age of disappearance was 1.5 months, and no TIF persisted after 7 months old. No relationship was noted between the TIF resolution and abnormal neurological signs or gross or fine motor development. The only association noted between age of resolution of the TIF and the neurodevelopmental status was a delay in language attainment at the 12-month screening. CONCLUSIONS: The TIF posture in infancy was noted in 65% of our cohort, and it had resolved in all infants by 7 months old. Therefore, a TIF posture after this age should alert the clinician to the possibility of possible neurological dysfunction. An unanticipated association of a delay in the 12-month language milestone attainment was noted in those infants with later resolution of the TIF posture. No data on language development in this group were obtained after 12 months old; therefore, the clinical significance of this finding is not yet elucidated.

Amelioration of polyuria in nephrogenic diabetes insipidus due to aquaporin-2 deficiency.

OBJECTIVE: We have recently reported a large cluster of patients with nephrogenic diabetes insipidus (NDI) due to an autosomal recessive aquaporin-2 (AQP-2) early-stop codon. This paper describes the clinical manifestations and evaluation of therapeutic approaches to this new entity. PATIENTS AND DESIGN: Nine patients with an AQP-2 mutation were studied. Urine osmolality was measured in five patients before and at 3 x 30 min intervals after desmopressin given in increasing doses of 5-100 micrograms. Urinary prostaglandins PGE2 and 6-keto PGF1 alpha, were extracted from 24-h urine samples and estimated by radioimmunoassays. Eight NDI patients were given a combination of a low-sodium diet and hydrochlorothiazide. Four to 11 weeks later, ibuprofen was added, and the patients were retested within the following 4-9 weeks. RESULTS: Urine osmolality remained unchanged after supra-pharmacological doses of desmopressin, at 60-70 mOsm/kg. Urinary PGE2 in control subjects was 0.74 +/- 0.1 microgram/g creatinine (mean +/- SD) compared to 5.0 +/- 2.6 micrograms/g creatinine in AQP-2 deficient patients (P < 0.05). Urinary 6-keto PGF1 alpha, was 0.20 +/- 0.03 microgram/g creatinine in controls and 0.75 +/- 0.31 microgram/g creatinine in AQP-2 deficiency (P < 0.05). Urinary volumes decreased by a mean 31% on a low-salt diet and hydrochlorothiazide, and by a mean of 38% on the combination therapy. Plasma osmolality decreased by a mean 15 mOsm/kg on the low-salt diet and hydrochlorothiazide, and by 22 mOsm/kg on the combination therapy. Urinary osmolality increased from a mean 80 mOsm/kg to 96 mOsm/kg on the low-salt diet and hydrochlorothiazide, and to 146 mOsm/kg on the combination therapy. CONCLUSION: AQP-2 deficiency in these patients with an early-stop codon is associated with complete unresponsiveness of the collecting duct to vasopressin, implying an indispensable role for AQP-2 in vasopressin antidiuresis. Urinary PGE2 and 6-keto PGF1 alpha are elevated, the former being extremely high, apparently due to the extreme vasopressin unresponsiveness. Combination therapy with a combination of a low-salt diet, thiazide and non-steroidal anti-inflammatory drug is partially effective.

Bone maturation in girls with Turner's syndrome.

The mechanism of growth retardation in Turner's syndrome has not been resolved. It is often referred to as a bone dysplasia, although endocrine derangement has not been ruled out. The present study was undertaken to evaluate the maturation of individual bones of the hand and wrist in girls with Turner's syndrome and thereby obtain information which may aid in elaborating the possible mechanism of the growth retardation in girls with Turner's syndrome. Hand and wrist films of 24 girls with Turner's syndrome, 11 normal girls with short stature and 23 normal controls were evaluated, using the references of Greulich and Pyle. Each bone or epiphysis was given an individual 'age'. During childhood the Turner patients showed the greatest delay in bone age of the phalangeal bones while the least delayed were the radius and ulna (long bones) and metacarpals. The carpal bones showed intermediate retardation. This pattern and extent of maturational retardation was clearly different from that of the short stature normal group, who showed uniform retardation of all bones. During adolescence, the phalangeal bones were further retarded and the carpal bones showed a moderate retardation. The unique profile of bone maturation in Turner's syndrome suggests an insult to chondroplasia, which may be related to estrogen deficiency or to an as yet undetermined endocrine or paracrine derangement.

Inherited inverted duplication of X chromosome in a male: report of a patient and review of the literature.

Nineteen cases of duplication of segments of the long arm of chromosome X have been published in 13 males and in 6 females. We report an additional case of a male with growth and mental retardation, growth hormone deficiency, compensated primary hypothyroidism, distinctive anomalies of the face, hypoplastic genitalia, and hypotonia in whom inverted duplication of a segment in the long arm of X chromosome was diagnosed, 46,Y, dup (X)(q21.2q13.3), and mosaicism was demonstrated in his mother's X chromosome. The rearranged segment was diagnosed utilizing high resolution G-band technique and FISH studies, using chromosome X total chromosome probe and DNA XIST probe. This appears to be the first report of a patient with duplication of Xq and hypothyroidism.

The clinical significance of rigors in febrile children.

UNLABELLED: The objective of the study was to evaluate the significance of rigor as a predictor of bacterial infection in hospitalized febrile infants and children. One hundred febrile children with rigor were studied and compared to 334 febrile matched controls without rigor. All underwent clinical evaluation and appropriate laboratory investigations. The patients were then divided into "bacterial" and "non bacterial" infection groups, as defined in the text. It was demonstrated that 66% of the patients with rigor belonged to the bacterial infection group versus 50% in the non-rigor group (P < 0.005). There was a significantly greater yield of positive blood cultures in the patients with rigor (P < 0.04), especially those over the age of 1 year (P < 0.015). The only laboratory examination of potential value as a predictor of bacterial infection in children with rigor was the band count. An absolute band count of more than 1500/mm was significantly more frequent in the rigor group (P < 0.003), and the combination of a rigor and band count of more than 1500 increased the relative risk for a bacterial infection by a factor of 1.35. These data demonstrate that rigor in hospitalized febrile infants or children significantly increase the likelihood of bacterial infection. CONCLUSION: Although the absence of rigors in febrile children does not exclude bacterial aetiology, their presence significantly increase the probability of an infection requiring appropriate workup and a reader institution of antibiotic therapy.

Stress hyperglycemia and the risk for the development of type 1 diabetes.

Transient hyperglycemia during acute illness may represent the earliest clinical sign of impaired beta cell function. This study sought to characterize the clinical presentation of patients with stress hyperglycemia and to determine the prevalence of immunologic and endocrinologic markers associated with prediabetes. Thirty-six children were studied. They were referred to us for routine evaluation after an episode of hyperglycemia during severe intercurrent illness. Immunologic markers (insulin autoantibodies and islet cell autoantibodies) and intravenous glucose tolerance test for evaluation of first phase insulin secretion rate were performed in all participants. Islet cell autoantibodies were negative in all patients. In eight patients, the first phase insulin response was below the first percentile (46 microU/ml) at the first determination. Insulin autoantibodies were positive in another three children (> 60 nU/ml). Twelve to sixteen months later, all children were re-evaluated and all had normal results. None of the patients developed diabetes during the study (mean 3.2 years). Our data support the idea that episodes of hyperglycemia during severe illness without additional risk factors are a minimal risk factor, if any, for future development of IDDM.

Autosomal recessive nephrogenic diabetes insipidus caused by an aquaporin-2 mutation.

Vasopressin V2 receptors, expressed from an x-chromosomal gene, are involved in antidiuresis, but also in release of coagulation factor VIII and von Willebrand factor (vWF). The present study describes autosomal recessive nephrogenic diabetes insipidus (NDI) in a large cluster of patients in Israel's Lower-Galilee. Evidence for an intact V2 receptor was concluded by their normal increase in factor VIII and vWF after desmopressin infusion. Thus, in these patients a defect in the pathway beyond the V2 receptor was suspected. The recent cloning of the human Aquaporin-2 gene enabled us to test this gene as a candidate for such a postreceptor defect. Direct sequencing of the Aquaporin-2 gene revealed a G298T substitution causing a Gly100Stop nonsense mutation in the third transmembrane region. Because this putative disease-causing mutation was identified in index patients of different families, we suggest that all patients are descendants of a common ancestor. Thus, this new entity is characterized by an autosomal recessive NDI. The differential response of clotting factors and urine osmolality to desmopressin may provide a simple tool for clinical diagnosis of a V2-postreceptor defect. The early stop-codon of Aquaporin-2 results in complete resistance to vasopressin antidiuretic effect.