Effect of electroacupuncture on arginine vasopressin-induced endolymphatic hydrops.

OBJECTIVE: To investigate the influence of electroacupuncture (EA) on experimentally induced endolymphatic hydrops (EH) in guinea pigs, and elucidate the association between the dehydrating effect of EA and changes in stria vascularis ultrastructure and expression of vasopressin type 2 receptor (V2R), cyclic adenosine monophosphate (cAMP), and aquaporin 2 (AQP2) in the endolymphatic sac (ES). METHODS: The EH model was established by intraperitoneal injection of arginine vasopressin (AVP). As a treatment, EA was delivered to Baihui (GV 20) and Tinggong (SI 19) acupoints, once daily for 10 consecutive days. For histomorphological studies, degree of cochlear hydrops was evaluated by hematoxylin-eosin staining, and the ratio of scala media (SM) area to SM + scala vestibuli area was calculated. In mechanical studies, ultrastructural changes in stria vascularis tissue were examined by transmission electron microscopy. In addition, cAMP levels and mRNA expression levels of V2R and AQP2 in the ES were compared among groups. RESULTS: EA treatment significantly reduced cochlear hydrops compared with hydropic guinea pigs (P = 0.015). Furthermore, EA attenuated ultrastructural changes in the stria vascularis tissue following EH, significantly upregulated the expression of V2R (P = 0.016), and attenuated AVP-induced upregulation of both cAMP (P = 0.038) and AQP2 expression (P = 0.017) in the ES. CONCLUSION: Collectively, the results of the present study suggest that the dehydrating effect of EA is associated with improvement of stria vascularis ultrastructure and V2R-cAMP-AQP2 signaling pathway regulation in the ES.

Recent Advances in the Management of Autosomal Dominant Polycystic Kidney Disease.

Autosomal dominant polycystic kidney disease (ADPKD), the most common monogenic cause of ESKD, is characterized by relentless development of kidney cysts, hypertension, and destruction of the kidney parenchyma. Over the past few years, major advancements in diagnosing, prognosticating, and understanding the pathogenesis and natural course of the disease have been made. Currently, no kidney disease is more suitable for nephron-protective strategies. Early nephrology referral and implementation of these strategies may have a substantial effect. Total kidney volume is a good prognostication marker and allows stratification of patients into slow or rapid progressing disease, with implications for their management. Measurement of total kidney volume, disease stratification, and prognostication are possible using readily available tools. Although some patients require only monitoring and basic optimized kidney protective measures, such as rigorous BP control and various lifestyle and dietary changes, others will benefit from disease-modifying treatments. Vasopressin V2 receptor antagonists, a likely disease-modifying treatment, has been approved in several countries and recently by the US Food and Drug Administration; other therapies, such as somatostatin analogs and other novel agents, are currently in clinical trials. The purpose of this article is to present our views on the optimal management to delay kidney disease progression in ADPKD.

Effect of Tolvaptan in Autosomal Dominant Polycystic Kidney Disease by CKD Stage: Results from the TEMPO 3:4 Trial.

BACKGROUND: and objectives The Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes 3:4 study demonstrated a significant beneficial effect of the vasopressin V2 receptor antagonist tolvaptan on rates of kidney growth and eGFR decline in autosomal dominant polycystic kidney disease (ADPKD). This post hoc analysis was performed to reassess the primary and secondary efficacy endpoints by CKD stage at baseline. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In a phase 3, multicenter, double-blind, placebo-controlled, 3-year trial, 1445 patients with ADPKD (age 18-50 years), with total kidney volume (TKV) ≥750 ml and estimated creatinine clearance ≥60 ml/min, were randomly assigned 2:1 to split-dose tolvaptan (45/15, 60/30, or 90/30 mg daily as tolerated) or placebo. The primary endpoint was annualized rate of TKV change. Secondary endpoints included a composite endpoint of time to multiple composite ADPKD-related events (worsening kidney function, kidney pain, hypertension, and albuminuria) and rate of kidney function decline. RESULTS: Tolvaptan reduced annualized TKV growth by 1.99%, 3.12%, and 2.61% per year (all P<0.001; subgroup-treatment interaction, P=0.17) and eGFR decline by 0.40 in CKD1 (P=0.23), 1.13 in CKD2 (P<0.001) and 1.66 ml/min per 1.73 m(2) per year in CKD3 (P<0.001) with a trend for a positive subgroup-treatment interaction (P=0.07) across CKD1, CKD2 and CKD3. ADPKD-related events were less frequent in tolvaptan recipients than in placebo recipients among those with CKD1 (hazard ratio [HR], 0.83; 95% confidence interval [95% CI], 0.70-0.98; P=0.03) and those with CKD 3 (HR, 0.71; 95% CI, 0.57-0.89; P=0.003), but not among those with CKD2 (HR, 1.02; 95% CI, 0.85-1.21; P=0.86). Aquaresis-related adverse events (more frequent in the tolvaptan group) and ADPKD-related adverse events (more frequent in the placebo group) were not associated with CKD stage. Hypernatremia events in tolvaptan-treated patients with CKD3 and plasma aminotransferase elevations in tolvaptan-treated patients across CKD stages 1-3 occurred more frequently than in placebo recipients. CONCLUSIONS: This post hoc analysis suggests clinically similar beneficial effects of tolvaptan in ADPKD across CKD stages 1-3.

Conivaptan therapy in an infant with severe hyponatremia and congestive heart failure.

Conivaptan is a nonspecific arginine vasopressin receptor antagonist that has been used as therapy in adults who have hypervolemic hyponatremia due to congestive heart failure. Its use in children with congestive heart failure has not been reported. We describe the use of conivaptan in a 4-month-old infant girl with severe hypervolemic hyponatremia and heart failure. A therapeutic weight-based dose was extrapolated from the adult dose. Conivaptan therapy was administered for 48 hours, after which the patient recovered from her hyponatremia without untoward effects. Arginine vasopressin receptor antagonists such as conivaptan may be useful as therapy for hyponatremia associated with heart failure. Further studies are required before conivaptan can be recommended for routine use in children.

Plasmatic vasopressin in patients undergoing conventional infra-renal abdominal aorta aneurysm repair / Vasopressina plasmática em pacientes submetidos à correção de aneurisma de aorta infrarrenal

OBJECTIVES: To evaluate plasmatic arginine vasopressin (AVP) levels in patients undergoing scheduled conventional abdominal aortic aneurysm (AAA) repair. METHODS: Plasmatic AVP concentrations were measured by radioimmunoassay in 22 non-consecutive adult patients undergoing infra-renal AAA repair. They were under combined general and epidural anesthesia at the following time frames: 1 - pre-operative (T0); 2 - 2h (T1) and 6h (T2) after the surgical procedure; 3 - in the morning at the first (T3), second (T4) and third (T5) post-operative days. Some clinical and laboratory variables were also recorded. RESULTS: The mean age of patients was 68±10 years; 17 were males. Plasmatic AVP (mean±SD; pg/mL) was within the normal range at T0 (1.4±0.7; baseline), increasing significantly at T1 (62.6±62.9; P<0.001) and at T2 (31.5±49.7; P<0.001), with a progressive fall, returning to basal levels at T5 (2.1±3.8; P=NS). Positive and statistically significant correlations were found between AVP and glycemia, serum lactate and white blood cells counts, but not with systemic arterial pressure or plasma osmolarity during the postoperative period. CONCLUSIONS: Considering that no correlations were found between AVP levels and hemodynamic or plasmatic osmolarity variations in AAA repair, it seems that stress response is mainly secondary to noxious stimulation mediated by the autonomic nervous system that is not completely blocked by anesthetics.

OBJETIVOS: Avaliar os níveis plasmáticos de vasopressina (AVP) em pacientes submetidos à correção convencional de aneurisma de aorta abdominal (AAA). MÉTODOS: A AVP plasmática foi mensurada por radioimunoensaio em 22 pacientes não-consecutivos submetidos à correção eletiva de AAA infrarrenal sob anestesia geral + epidural nos seguintes momentos: pré-operatório (T0); 2h (T1) e 6h (T2) após a cirurgia; e nas manhãs do primeiro (T3), segundo (T4) e terceiro (T5) dia pós-operatório (PO). Variáveis clínicas e laboratoriais de interesse também foram anotadas. RESULTADOS: A média de idade dos pacientes foi de 68±10 anos, sendo 17 homens. A AVP plasmática (média±DP; pg/ mL) estava dentro de limites normais no T0 (1,4±0,7; basal), aumentando no T1 (62,6±62,9; P<0,001) e no T2 (31,5±49,7; P<0,001), e retornando aos valores basais no T5 (2,1±3,8; P=NS). Correlações positivas e significativas foram encontradas entre a AVP e glicemia, lactato sérico e leucócitos sanguíneos, mas não com a pressão arterial sistêmica ou com a osmolaridade plasmática no PO. CONCLUSÕES: Na cirurgia de reparação de AAA, considerando que nenhuma correlação foi encontrada entre os níveis de AVP e variações hemodinâmicas ou da osmolaridade plasmática, este achado sugere que a resposta ao estresse é predominantemente secundária aos estímulos dolorosos mediados pela parte autônoma do sistema nervoso, não completamente bloqueados pelos anestésicos.

Identification of a mutation in the arginine vasopressin receptor 2 gene in a Chinese pedigree with congenital nephrogenic diabetes insipidus / 中华内分泌代谢杂志

Genomic DNA was extracted from the blood samples of 3 patients from 1 pedigree with congenital nephrogenie diabetes insipidus (NDI) and their 12 family members.The whole coding region of the arginine vasopressin receptor 2 (AVPR2) gene was amplified by PCR and then directly sequenced,A mutation of AVPR2 gene [g1236T→C (L292P)]was found in 3 patients.The patients' mothers were found to have both mutant and normal alleles.