Clinicopathological Features of Gitelman Syndrome with Proteinuria and Renal Dysfunction.

INTRODUCTION: Gitelman syndrome (GS) is a rare renal tubular salt-wasting disorder. Besides kidney electrolyte loss, proteinuria and renal dysfunction were also observed. However, their incidence, risk factors, pathological features, and prognosis were unclear. METHODS: We retrospectively reviewed 116 GS patients and analyzed their clinical, genetic, and pathological characteristics. We also systematically reviewed articles on GS with proteinuria and renal dysfunction. RESULTS: Twenty-three GS patients had proteinuria (69.6%) and renal dysfunction (43.5%) with a mean age of 35.3 ± 13.2 years, and 65.2% were male. Compared to patients without proteinuria or renal dysfunction, these patients had elevated plasma angiotensin II level (440.2 ± 351.7 vs. 253.2 ± 187.4 pg/mL, p = 0.031) and three times higher incidence of diabetes. The renal pathology of nine biopsied patients indicated hypertrophy of the juxtaglomerular apparatus (100%), chronic tubulointerstitial changes (66.7%), intrarenal vascular changes (66.7%), and glomerulopathy (55.6%). More extensive renin staining was observed in patients with GS than in the control group with glomerular minor lesion (p < 0.001). During a median of 85 months (range, 11-205 months) of follow-up for 19 out of the 23 GS-renal patients, the renal function was generally stable, except one died of cancer and one developed end-stage renal disease because of concomitant membranous nephropathy and IgA nephropathy. CONCLUSION: Proteinuria and renal dysfunction were more common than expected and might indicate glomerulopathy and vascular lesions besides a tubulointerstitial injury in GS. Renal function may maintain stable with effective therapy in most cases.

Frequent SLC12A3 mutations in Chinese Gitelman syndrome patients: structure and function disorder.

Purposes: This study was conducted to identify the frequent mutations from reported Chinese Gitelman syndrome (GS) patients, to predict the three-dimensional structure change of human Na-Cl co-transporter (hNCC), and to test the activity of these mutations and some novel mutations in vitro and in vivo. Methods: SLC12A3 gene mutations in Chinese GS patients previously reported in the PubMed, China National Knowledge Infrastructure, and Wanfang database were summarized. Predicted configurations of wild type (WT) and mutant proteins were achieved using the I-TASSER workplace. Six missense mutations (T60M, L215F, D486N, N534K, Q617R, and R928C) were generated by site-directed mutagenesis. 22Na+ uptake experiment was carried out in the Xenopus laevisoocyte expression system. In the study, 35 GS patients and 20 healthy volunteers underwent the thiazide test. Results: T60M, T163M, D486N, R913Q, R928C, and R959frameshift were frequent SLC12A3 gene mutations (mutated frequency >3%) in 310 Chinese GS families. The protein's three-dimensional structure was predicted to be altered in all mutations. Compared with WT hNCC, the thiazide-sensitive 22Na+ uptake was significantly diminished for all six mutations: T60M 22 ± 9.2%, R928C 29 ± 12%, L215F 38 ± 14%, N534K 41 ± 15.5%, Q617R 63 ± 22.1%, and D486N 77 ± 20.4%. In thiazide test, the net increase in chloride fractional excretion in 20 healthy controls was significantly higher than GS patients with or without T60M or D486N mutations. Conclusions: Frequent mutations (T60M, D486N, and R928C) and novel mutations (L215F, N534K, and Q617R) lead to protein structure alternation and protein dysfunction verified by 22Na+ uptake experiment in vitro and thiazide test on the patients.

Bridging "Office-Based Care" With the "Virtual Practice Care Model": Evolving Care for Chronic Kidney Disease Patients in the COVID-19 Pandemic-And Beyond.

Since the outbreak of the coronavirus epidemic, the "virtual" telemedicine has become a critical substitute for patient-provider interactions. However, virtual encounters often face challenges in the care of patients in high-risk categories such as chronic kidney disease (CKD) patients. In this study, we explore the patient's satisfaction and the practical effects of a newly established telemedicine program on CKD patients' care during the COVID-19 pandemic. Based on a prior version of an online patient care platform established in 2017, we developed a customized and improved online telemedicine program designed to specifically address the challenges emerging from the pandemic. This included an online, smart phone-based strategy for triage and medical care delivery and psychological support. We invited a total of 278 CKD patients to join the new platform during the pandemic. The subjects in group A were patients utilizing our old online CKD system and were historical users registered at least 3 months before the pandemic. A pilot survey interrogating medical and psychological conditions was conducted. Feedback on the program as well as a psychological assessment were collected after 1 month. In total, 181 patients showed active responses to the program, with 289 person-time medical consultations occurring during the study. The virtual care program provided a rapid triage for 17% (30 out of 181) patients, with timely referral to in-patient medical encounters for their worsening medical conditions or severe psychological problems. Nearly all patients (97.4%) believed the program was helpful. The number of symptoms (OR 1.309, 95%CI 1.113-1.541; P = 0.001) and being enrolled during the pandemic (OR 3.939, 95% CI 1.174-13.221; P = 0.026) were associated with high stress. During the follow-up, the high-stress CKD group at baseline showed a significant decrease in avoidance score (6.9 ± 4.7 vs. 9.8 ± 1.9, P = 0.015). In conclusion, during the pandemic, we established an online telemedicine care program for CKD patients that provides a rapid triage function, effective CKD disease management, and potentially essential psychological support.

Clinical and laboratory features of female Gitelman syndrome and the pregnancy outcomes in a Chinese cohort.

AIM: Gitelman syndrome (GS) is a rare inherited salt-losing renal tubulopathy. Data on clinical features and the pregnancy outcome for female GS patients in a large cohort are lacking. The study was aimed to explore the phenotype and pregnant issue for female GS patients. METHODS: GS cases from the National Rare Diseases Registry System of China (NRSC) were collected, and detailed clinical, laboratory and genetic data were analysed. Articles on pregnancy in GS were also systemically reviewed. RESULTS: A total of 101 GS patients were included; among them, 42.6% were female and 79.2% showed hypomagnesaemia. A lower proportion of female patients presented before 18 years of age, with less frequently reported polyuria, higher serum potassium and less urine sodium and chloride excretions. There was no gender difference in the sodium-chloride cotransporter (NCC) dysfunction evaluated by hydrochlorothiazide test. Twelve of the 43 female GS patients delivered after disease symptom onset, and their pregnancies were generally uneventful. As a group, pregnant GS patients had lower potassium levels in the first-trimester (P = .002) requiring higher potassium supplementation. After delivery, serum potassium (P = .02) and magnesium (P = .03) increased significantly. Both caesarean section and vaginal delivery were safe. CONCLUSION: Female GS patients may have a less severe phenotype with generally favourable outcomes of pregnancy. Intensive monitoring and increased potassium supplementation are necessary during pregnancy, especially in the first-trimester.

Hydrochlorothiazide Test as a Tool in the Diagnosis of Gitelman Syndrome in Chinese Patients.

Traditional clinical diagnostic criteria for Gitelman syndrome (GS) including hypomagnesemia and hypocalciuria have been challenged by reports of atypical manifestations recently, as well as the development of genetic testing. Hydrochlorothiazide (HCT) test is a diagnostic method different from the traditional biochemical parameters, which could evaluate the function of thiazide-sensitive sodium-chloride co-transporter (NCC) in vivo by a small dose of NCC inhibitor HCT. In this retrospective study, we compared the diagnostic significance of hypomagnesemia, hypocalciuria, and the reaction of HCT test, among Chinese patients with GS confirmed by genetic test. For patients who were clinically suspected of GS manifestations, SLC12A3 gene was sequenced to make genetic diagnosis. A total of 83 GS and 19 control patients were recruited, among which 37 underwent HCT test according to the standard process. Compared with the gold standard of genetic diagnosis, both the diagnostic sensitivity (93.10%) and specificity (100.00%) of the HCT test were much higher than those of hypomagnesemia and/or hypocalciuria. The area under the receiver operating characteristic (ROC) curve was 1.000 (95% CI 0.905-1.000) for HCT test, higher than the values using hypomagnesemia and/or hypocalciuria. The cost of HCT test was around $54, much lower than genetic diagnosis. In conclusion, besides traditional hypomagnesemia and hypocalciuria, HCT test could be a valuable tool in the clinical diagnosis of Chinese GS patients.

Ethical dilemma of identity disclosure faced by medical students in clinical clerkships: A nationwide multicenter study in China.

OBJECTIVE: Medical students in China are currently facing a dilemma of whether to clarify their identity as students to patients. Further investigation is needed to support policy-making. The aim was to identify factors influencing medical students' decision on whether or not to clarify their identity to patients and to examine the effects of their decision. METHODS: The study was a cross-sectional nationwide multicenter survey consisting of 947 medical students. A self-designed questionnaire was composed of 19 structured questions investigating the present situation and participants' perception of the ethical dilemma surrounding medical student identity. The questionnaires were distributed randomly in teaching hospitals affiliated with 13 medical schools across China from June 2015 to January 2016. RESULTS: A total of 947 valid questionnaires were retrieved with a valid response rate of 83.7%. Most medical students (71.4%) tended to be ambiguous about their student identity in front of patients. The frequency of encountering distrust and patients' or patient relatives' refusal to allow students to perform procedures was significantly lower for students who explicitly stated their identity than for those who were ambiguous about their identity (p<0.001). Less experience in clinical rotations (<0.5 y/0.5-1 y, OR 2.7, 95% CI 1.7-4.3; <0.5 y/>1 y, OR 3.6, 95% CI 2.0-6.5), preceptors' straightforward introduction of the students (OR 8.7, 95% CI 5.4-13.8) and students' acknowledgment of patients' right to know (OR 2.3, 95% CI 1.2-4.5) were related to students' clear self-introduction to patients. CONCLUSION: It is beneficial for medical students to clearly explain their identity to patients in order to decrease patient distrust and prevent the refusal to have certain appropriate procedures performed. Several methods, including emphasizing the role of mentors, developing curriculum for medical students, and creating clear regulations and guidelines for revealing the identity of medical students on the healthcare team can help address and ideally resolve this ethical dilemma of identity disclosure.

Co-Occurrence of Pheochromocytoma-Paraganglioma and Cyanotic Congenital Heart Disease: A Case Report and Literature Review.

Pheochromocytoma and paraganglioma (PHEO-PGL) and cyanotic congenital heart disease (CCHD) are both rare diseases. We reported a 30-year-old patient with a right adrenal gland nodule and a retroperitoneal mass and history of functional single atrium and ventricle. 123I-metaiodobenzylguanidine scintigraphy showed intense uptake in both lesions. Laboratory investigation demonstrated elevated urinary norepinephrine. Preoperative α-blockade was initiated. A successful open resection of right adrenal and retroperitoneal masses was performed. Pathological examination confirmed PHEO-PGL. Postoperative urinary norepinephrine returned to normal level. A systematic case review in English publications in PubMed and EMBASE suggested a hypothesis that there may exist a possible link between PHEO-PGL and hypoxia from CCHD, which was also indicated in our case. Due to higher risk for PHEO-PGL, a lower threshold of suspicion should be considered in CCHD patients. Therefore, active screening and early treatment of PHEO-PGL are recommended in CCHD patients and clinicians should keep on a long-term follow-up to monitor PHEO-PGL recurrence if hypoxia is not corrected.