Mutation Analysis of AVPR2 and AQP2 Gene in Chinese Patients with Congenital Nephrogenic Diabetes Insipidus

To detect mutations of the aquaporin 2 gene（AQP2） and the arginine vasopressin V2 receptor gene（AVPR2） of Chinese congenital nephrogenic diabetes insipidus, and to establish the foundation for further studying the emergence mechanism of the disease and clinical diagnosis, all the exons and part of introns of AQP2 and AVPR2 genes were amplified with intronic primers, using genomic DNA extracted from three patients with congenital nephrogenic diabetes insipidus and two mothers as template, PCR product was ligated into a T-vector and then sequenced. The result was compared with the database sequence to identify the mutable sites via a BLAST search, the incidence of every mutation was analyzed, and the putative transcription factor binding sites that maybe disturbed were analyzed by MAPPER. Mutation g.1394A〉G in exon 3 of AVPR2 was detected in all the subjects, g.861C〉T（S167L） in exon 2 of AVPR2 and IVS1＋3G〉A in intron of AQP2 were detected, respectively, in two patients, and c.836A〉C in 3′ untranslated region of AQP2 was detected in two patients and one mother. Four mutations were identified. g.1394A〉G of AVPR2 and c.836A〉C of AQP2 have high incidence in patients with nephrogenic diabetes insipidus. Detection on the two sites may become auxiliary diagnosis index of congenital nephrogenic diabetes insipidus.

Postsurgical Evaluation of Secondary Nephrogenic Hyperparathyroidism

Parathyroidectomy is useful for the treatment of secondary hyperparathyroidism(SHPT)caused by chronic renal failure.The following three types of parathyroidectomy can be performed:subtotal parathyroidectomy,total parathyroidectomy and total parathyroidectomy plus autologous transplantation(tPTX+AT).Each of the three types of surgery has advantages and disadvantages.The present study retrospectively analyzed the efficacy of tPTX+AT for the treatment of SHPT over 1 year.Thirty-seven patients who were diagnosed with secondary nephrogenic hyperparathyroidism and treated with tPTX+AT were selected between September 2014 and October 2016 and followed up for 1 year.Their average age was 66.5±46.0 years,and the average time of dialysis was 48.1±8.2 months.The patients1 conditions,including the levels of intact parathyroid hormone(iPTH)and bone metabolism,were compared preoperatively and 1 and 7 days and 1,3,6 and 12 months after surgery.In addition,the postoperative complications,pathological data,SHPT recurrence and prognosis were examined.The results showed that the postoperative level of ostalgia and cutaneous pruritus significantly decreased in the patients.An inspection of the parathyroid tissues during the operation confimied the presence of parathyroid gland hyperplasia with no carcinoma detected?Three patients with hoarseness recovered within 1 month,and 1 patient with unilateral recurrent laryngeal nerve injury improved after 6 months of voice training.Conipared to the preoperative condition,the postoperative serum iPTH,serum calcium and serum phosphate levels were significantly decreased(P<0.001),and these differences remained significant 12 months after surgery.Compared to the preoperative condition,the alkaline phosphatase(ALP)concentration was decreased on postoperative day 1(P<0.05),but no differences were observed on day 7 or at 1 month(P>0.05).The ALP levels continuously decreased at 3,6 and 12 months(P<0.01).In conclusion,tPTX+AT significantly improves the quality of life and serum biomarker levels of these patients.The convenient surgical removal of the hyperplastic parathyroid gland for postoperative recurrence supports tPTX+AT as the recommended treatment for relevant patients.

Nephrogenic systemic fibrosis:A frivolous entity

Gadolinium-based contrast agents(GBCAs)used in magnetic resonance imaging are vital in providing enhanced quality images,essential for diagnosis and treatment.Nephrogenic systemic fibrosis(NSF)with GBCAs has been a deterrent for the physician and has led to avoidance of these agents in patients with impaired kidney function.NSF is a progressive debilitating multisystem condition described classically in patients with renal insufficiency exposed to gadolinium contrast media.It is characterized by an induration and hardening of the skin.NSF is described to first involve the extremities and can imperceptibly involve internal organs.Lack of therapeutic interventions to treat NSF makes it more challenging and warrants deep insight into the pathogenesis,risk factors and treatment strategies.

Pathophysiology of nephrogenic systemic fibrosis:A review of experimental data

Since the association between nephrogenic systemic fibrosis(NSF) and gadolinium contrast agents(Gd-CAs) was suggested in 2006,several experimental studies have been published to elucidate the role of these agents in the pathogenesis of NSF.Low stability Gd-CAs have a stimulant effect on human skin and fibroblasts in culture and modulate the production of collagen by these cells.Low stability agents have also induced NSFlike skin changes in a rat model with normal renal function after multiple repeat administrations.The role of the 5/6 subtotal nephrectomy rat model in investigating NSF remains under evaluation.

Congenital nephrogenic diabetes insipidus due to the mutation in AVPR2(c.541C>T)in a neonate:A case report

BACKGROUND Congenital nephrogenic diabetes insipidus (CNDI) is a rare hereditary renaldisorder that is caused by mutations in AVPR2 or aquaporin 2 (AQP2). Up tonow, there are few reports about CNDI in neonates. Early clinical manifestationsof CNDI in neonates are atypical. A lack of understanding of the disease byclinicians causes frequent misdiagnoses or missed diagnoses, which may result infailure to administer treatments in time and ultimately leads to severecomplications. In this study, clinical data of a case of AVPR2 gene mutationinducedCNDI, which was confirmed by genetic testing, were retrospectivelyanalyzed to improve our understanding of this disease.CASE SUMMARY On February 1, 2020, a male neonate was hospitalized 17 d after birth due to a 7 dperiod of pyrexia. The patient’s symptoms included recurrent pyrexia,hypernatremia and hyperchloremia, which were difficult to treat. The patient wasfed on demand, and water was additionally provided between milk intakes. Acombination treatment of hydrochlorothiazide and amiloride was administered.After the treatment, body temperature and electrolyte levels returned to normal,the volume of urine was significantly reduced and the patient was subsequentlydischarged. Genetic tests confirmed that the patient carried the AVPR2 genemissense mutation c.541C>T (P.R181C), and the patient’s mother carried aheterozygous mutation at the same locus. After clinical treatment with acombination of hydrochlorothiazide and amiloride, the body temperature andelectrolyte levels returned to normal. Up until the most recent follow-up examination, normal body temperature, electrolyte levels and growth anddevelopment were observed.CONCLUSION CNDI in the neonatal period is rare, and its clinical manifestations are unspecificwith some patients merely showing recurrent fever and electrolyte disturbance.Genetic testing of AVPR2 and AQP2 can be used for screening and geneticdiagnosis of CNDI.

Congenital nephrogenic diabetes insipidus arginine vasopressin receptor 2 gene mutation at new site:A case report

BACKGROUND Congenital nephrogenic diabetes insipidus(CNDI)is a rare hereditary disorder.It is associated with mutations in the arginine vasopressin receptor 2(AVPR2)gene and aquaporin 2(AQP2)gene,and approximately 270 different mutation sites have been reported for AVPR2.Therefore,new mutations and new manifestations are crucial to complement the clinical deficiencies in the diagnosis of this disease.We report a case of a novel AVPR2 gene mutation locus and a new clinical manifestation.CASE SUMMARY We describe the case of a 48-d-old boy who presented with recurrent fever and diarrhea 5 d after birth.Laboratory tests showed electrolyte disturbances and low urine specific gravity,and imaging tests showed no abnormalities.Genetic testing revealed a novel X-linked recessive missense mutation,c.283(exon 2)C>T(p.P95S).This mutation results in the substitution of a proline residue with a serine residue in the AVPR2 protein sequence.The diagnosis of CNDI was confirmed based on the AVPR2 gene mutation.The treatment strategy for this patient was divided into two stages,including physical cooling supplemented with appropriate amounts of water in the early stage and oral hydrochlorothiazide(1-2 mg/kg)after a clear diagnosis.After follow-up of one and a half years,the patient gradually improved.CONCLUSION AVPR2 gene mutations in new loci and new clinical symptoms help clinicians understand this disease and shorten the diagnosis cycle.

Magnetic resonance venography and liver transplant complications

Hepatic vein stenosis is a rare but serious complication following liver transplantation.Multiple modalities can be utilized to image the hepatic vasculature.Magnetic resonance venography(MRV)provides certain advantages over ultrasound,computed tomography angiography and digital subtraction venography.MRV utilizes the same imaging principles of magnetic resonance angiography in order to image the venous system.Blood pool contrast agents,specifically gadofosveset trisodium,allow for steady state imaging up to 1 h following injection,with improved visualisation of vital venous structures by utilising delayed steady state imaging.Additionally,the inherent physics properties of magnetic resonance imaging also provide excellent soft tissue detail and thus help define the extent of complications that often plague the post-liver transplant patient.This case report describes the use of gadofosveset trisodium in a patient with hepatic venous stenosis following liver transplantation.Initial venography failed to outline the stenoses and thus MRV using a blood pool contrast agent was utilised in order to delineate the anatomy and plan a therapeutic endovascular procedure.

Prolonged hypernatremia triggered by hyperglycemic hyperosmolar state with coma: A case report

A man with past lithium use for more than 15 years, but off lithium for two years and not carrying the diagnosis of diabetes mellitus or nephrogenic diabetes insipidus(NDI), presented with coma and hyperglycemic hyperosmolar state(HHS). Following correction of HHS, he developed persistent hypernatremia accompanied by large volumes of urine with low osmolality and no response to desmopressin injections. Urine osmolality remained < 300 m Osm/kg after injection of vasopressin. Improvement in serum sodium concentration followed the intake of large volumes of water plus administration of amiloride and hydrochlorothiazide. Severe hyperglycemia may trigger symptomatic lithium-induced NDI years after cessation of lithium therapy. Patients with newonset diabetes mellitus who had been on prolonged lithium therapy in the past require monitoring of their serum sodium concentration after hyperglycemic episodes regardless of whether they do or do not carry the diagnosis of NDI.

Contrast enhanced multi-detector CT and MR findings of a well-differentiated pancreatic vipoma

Pancreatic vipoma is an extremely rare tumor accounting for less than 2% of endocrine pancreatic neoplasms with a reported incidence of 0.1-0.6 per million. While cross-sectional imaging findings are usually not specific, exact localization of the tumor by means of either computed tomography(CT) or magnetic resonance(MR) is pivotal for surgical planning. However, cross-sectional imaging findings are usually not specific and further characterization of the tumor may only be achieved bysomatostatin-receptor scintigraphy(SRS). We report the case of a 70 years old female with a two years history of watery diarrhoea who was found to have a solid, inhomogeneously enhancing lesion at the level of the pancreatic tail at Gadolinium-enhanced MR(Somatom Trio 3T, Siemens, Germany). The tumor had been prospectively overlooked at a contrast-enhanced multi-detector CT(Aquilion 64, Toshiba, Japan) performed after i.v. bolus injection of only 100 cc of iodinated non ionic contrast media because of a chronic renal failure(3.4 mg/mL) but it was subsequently confirmed by SRS. The patient first underwent a successful symptomatic treatment with somatostatin analogues and was then submitted to a distal pancreasectomy with splenectomy to remove a capsulated whitish tumor which turned out to be a well-differentiated vipoma at histological and immuno-histochemical analysis.

Evaluation of a handheld creatinine measurement device for real-time determination of serum creatinine in radiology departments

AIM: To assess the feasibility/accuracy of a commercial handheld device in the context of increased demand for point-of-care serum creatinine (SCr) determination. METHODS: In this institutional review board-approved, prospective study, 401 patients referred for contrastenhanced computed tomography were included at two centres. Capillary (c)SCr was determined using two devices A+B and venous (v)SCr was determined in the centre's laboratory. Method comparison statistics for both centres and for vSCr<>1.2 mg/dL, receiver operating characteristic analysis, negative predictive values (NPV), sensitivity and specificity were calculated pre-/ post-curve offset correction with vSCr. RESULTS: Pearson's coefficients for cSCr vs vSCr were: centre 1-A:0.93/B:0.92; centre 2-A:0.85/B:0.82 (all P < 0.0001). Overall correlation was better for vSCr > 1.2 mg/dL. The area under the receiver operating characteristic curves showed a high accuracy for cSCr, but the device underestimated SCr, which was confirmed by Bland-Altman plot. Addition of the offset correction factor to the original data from centre 1 resulted in an improvement in sensitivity for detecting patients at risk (> 1.2 mg/dL), whilst maintaining acceptable specificity and improving NPV. CONCLUSION: This study showed the feasibility of SCr determination using the evaluated handheld device in a routine clinical setting. The device showed high sensitivity and high NPV, but may significantly underestimate SCr without offset correction to local laboratories.

Lanthanides-Induced Cellular Signal Transduction: Implications in Pathogenesis of Fibrosis

With the extensive mining and application of lanthanides in China and worldwide, the potential impact of lanthanides on human health is gaining increasing attentions. The recent etiological association of gadolinium-based contrast agents with nephrogenic systemic fibrosis (NSF) evoked widespread concerns regarding the safety issue of lanthanides. The elucidation of the cellular biological effects of and the signalling cascade induced lanthanides is essential for proper evaluation of their health impacts.

From Russia with Polyuria

Introduction: Polyuria is a sign for many disease processes, including diabetes mellitus and diabetes insipidus. Urine osmolarity helps distinguish osmotic diuresis caused by diabetes mellitus from water dieresis induced by diabetes insipidus. Case Presentation: We report a case of a 48-year-old woman who presented with polyuria, polydipsia, nocturia, and weight loss after a return from a visit to Russia, during which she received a five-day course of antibiotic Demeclocycline, a tetracycline derivative for dental treatment. She recovered from all clinical manifestations by 8 weeks. Conclusion: Manifestation of transient nephrogenic diabetes insipidus is induced by Demeclocycline.