Approach to the Patient: Hyponatremia and the Syndrome of Inappropriate Antidiuresis (SIAD).

Hyponatremia is the most common electrolyte disturbance seen in clinical practice, affecting up to 30% of acute hospital admissions, and is associated with significant adverse clinical outcomes. Acute or severe symptomatic hyponatremia carries a high risk of neurological morbidity and mortality. In contrast, chronic hyponatremia is associated with significant morbidity including increased risk of falls, osteoporosis, fractures, gait instability, and cognitive decline; prolonged hospital admissions; and etiology-specific increase in mortality. In this Approach to the Patient, we review and compare the current recommendations, guidelines, and literature for diagnosis and treatment options for both acute and chronic hyponatremia, illustrated by 2 case studies. Particular focus is concentrated on the diagnosis and management of the syndrome of inappropriate antidiuresis. An understanding of the pathophysiology of hyponatremia, along with a synthesis of the duration of hyponatremia, biochemical severity, symptomatology, and blood volume status, forms the structure to guide the appropriate and timely management of hyponatremia. We present 2 illustrative cases that represent common presentations with hyponatremia and discuss the approach to management of these and other causes of hyponatremia.

The Effect of Dietary Intervention on Autosomal-Dominant Polycystic Kidney Disease (ADPKD) Patients on Tolvaptan and Their Quality of Life.

Background and objective Autosomal-dominant polycystic kidney disease (ADPKD) is the most common inherited renal disorder; it affects people of all ethnic groups and is found in up to 10% of patients with end-stage renal disease (ESRD). Dietary intervention is important in people with renal disease, and it has been linked to greater estimated glomerular filtration rate (eGFR) preservation. Tolvaptan, an orally-active nonpeptide, selective arginine vasopressin (AVP) V2R antagonist, was recently licensed in numerous countries for the treatment of ADPKD. The aim of this study was to assess the role of dietary intervention in decreasing the osmotic load on the urine volume and its impact on the quality of life (QOL) of patients with ADPKD on tolvaptan. Methods This prospective cohort study was carried out at a Hamilton nephrology genetics clinic. ADPKD patients on well-tolerated doses of tolvaptan for three months were included in the study. Gitelman and Bartter Symptom Health-related QOL questionnaire was used among the study participants. Results Our study consisted of nine adult patients with ADPKD who were on a stable dose of tolvaptan therapy. Patients had laboratory values for urine volume, sodium (Na), and urea. No significant difference was found between pre- and post-diet intervention values in 24-hour urine volume (5.9 vs. 5.49 L/d; p=0.423), urine Na (p=0.174), and 24-hour urine urea (p=0.404). Conclusion Dietary intervention in ADPKD patients on tolvaptan therapy can play a vital role in improving their QOL. Further research including interventional studies and clinical trials with larger sample sizes is needed to gain deeper insight into the subject.

A Case Report of Tolvaptan Therapy for ADPKD Patients With COVID-19. The Need for Appropriate Counselling for Temporary Drug Discontinuation.

BACKGROUND: Patients with autosomal dominant polycystic kidney disease (ADPKD) may require specific therapy with vasopressin receptor antagonists to slow the progression of renal disease. Because of its mechanism of action, the most common side effects are polyuria, nocturia, and polydipsia. Elevations of liver enzyme levels can also occur during treatment with Tolvaptan. Temporary drug withdrawal may be indicated if the patient is unable to hydrate adequately or if there are concomitant causes of dehydration, including major infectious events. During the Coronavirus Disease 2019 (COVID-19) pandemic, this should be considered in the management of patients on Tolvaptan therapy. CASE REPORT: We present the clinical case of a 51-year-old male with severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) infection and ADPKD receiving Tolvaptan therapy with particular reference to the medical management of the patient during the infectious event. The patient was instructed to discontinue promptly Tolvaptan as soon as symptoms appeared. He was treated with forced hydration and symptomatic therapy. Nevertheless, a transient elevation of liver enzyme levels was detected. The timely discontinuation of Tolvaptan therapy avoided the risk of potential hepatotoxicity in a condition of known susceptibility. CONCLUSION: Tolvaptan therapy of patients with ADPKD is safe even during SARS-CoV-2 infection. There is need for appropriate and prompt patient counseling to avoid potentially adverse side effects.

Outcomes from a dedicated Tolvaptan clinic for patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Introduction: Tolvaptan was approved for use in patients with ADPKD by the Scottish Medicines Consortium in January 2016, following the results of the TEMPO 3:4 trial, which showed that Tolvaptan reduced the rate of decline in kidney function- and increase in total kidney volume- compared to placebo.1 In July 2017, a dedicated Tolvaptan clinic was set up for patients with ADPKD from NHS Greater Glasgow and Clyde and NHS Forth Valley. Eligible patients are referred from their local general nephrology clinic, and counselled on treatment with Tolvaptan by a dedicated team comprised of consultant nephrologists, advanced nurse practitioners and renal pharmacists. Those who choose to proceed with treatment are reviewed monthly in the ADPKD clinic for the first 18 months of treatment before returning to three monthly follow up at their local nephrology clinic.We aimed to analyse the outcomes of patients referred to the ADPKD clinic since July 2017. Method: All patients referred to the Glasgow ADPKD clinic between July 2017 and January 2021 were identified. Prospectively recorded data was collected from SERPR and Clinical Portal and analysed retrospectively. In those who did not commence treatment with Tolvaptan, the documented reason was recorded. In those who commenced Tolvaptan, further data were gathered including duration of treatment, dose achieved, side effects reported, any LFT derangement, and serum creatinine measurements over time. An assessment of whether patients met the Renal Association criteria for eligibility for treatment with Tolvaptan was also made. Results: 78 patients who attended the ADPKD clinic were identified. 60 patients commenced treatment with Tolvaptan. Of those who did not start treatment, the most common reason recorded was anticipated side effects and consequent impact upon quality of life (7/18 patients). 25 of the 60 patients who started Tolvaptan stopped the drug during this period, after a median length of treatment of 11 months (IQR 2-18 months). The most common reason for stopping Tolvaptan was also side effects -23% of our patients stopped for this reason compared to 8% in the trial. The median length of treatment in those patients still on Tolvaptan was 21 months (IQR 14-34.5 months). 29 patients had a break in treatment due to the COVID-19 pandemic. 7 patients (11.7%) had treatment suspended due to deranged LFTs, and 2 (3.3%) of those patients did not resume Tolvaptan, compared to 1.2% of patients in the trial. In retrospect, 4 of the 60 patients commenced on treatment may not have met the criteria for eligibility for treatment with Tolvaptan suggested by the Renal Association. Discussion: Tolvaptan appears to be well-tolerated in the majority of patients. As expected, a significant minority of patients do not tolerate Tolvaptan due to expected side effects. A higher proportion of our patients stopped Tolvaptan due to aquaresis side effects that in TEMPO, but this is not unexpected, and the vast majority of patients in our clinic elected to resume Tolvaptan after an enforced break due to the COVID-19 pandemic. Fewer patients in our clinic were maintained on less than full dose Tolvaptan when compared with the trial. A higher percentage of our patients had Tolvaptan discontinued due to deranged LFTs than in the trial, although this was only 2 patients. The impact of Tolvaptan on CKD progression outwith the trial setting will become clearer over time.

eP270: Incorporating genetic services into adult kidney disease care

Introduction: Chronic kidney disease (CKD) is a debilitating disorder associated with significant morbidity and mortality. CKD diagnoses can have overlapping, non-specific clinical symptoms and histology findings, and the underlying etiology can remain unknown. Recent studies have shown that 1 in 10 adults with CKD has a genetic component to their disease. However, genetic services are limited in this patient population and disproportionally impact those from medically underserved communities. Therefore, an adult kidney genetics clinic was developed within the Division of Nephrology at a large urban academic medical center to increase access to genetic services and testing in adults with kidney disease. Methods: In June 2019, the Division of Nephrology at Columbia University Irving Medical Center created a Kidney Genetics Clinic staffed by genetic counselors (GC) and nephrologists. Initially, appointments were held in-person but transitioned to telemedicine beginning in May 2020 due to the COVID-19 pandemic. The clinic utilized two appointment types: full genetic consults (staffed by a GC and nephrologist) and genetic counseling visits (staffed by a GC only). Genetic counselors implemented several genetic education initiatives to increase clinic referrals and increase provider interest. These included bi-monthly genetic case seminars, monthly genetic research sign-out rounds, a continuing education course focusing on clinical genetics, and genetic counseling student rotations. Results: Between June 2019 and June 2021, the clinic received 277 referrals, averaging 11 per month. Of those referred, 83% were scheduled, and 212 patients underwent genetic evaluation. The median wait time from referral to appointment was 37 days, and the no-show rate was 8%. The majority (89%) of appointments were via telehealth, either by phone or video, while the rest occurred in person. Genetic counseling visits accounted for 21% of patient appointments, and the remaining ones were full genetic consults. Most patients who attended their genetics appointment were in the NY tri-state area (87%), but 12% resided in nine additional states, three other countries, and one US territory. The primary insurance was Medicare in 10% of patients and Medicaid in 17%. Most patients described themselves as white (n=126), while 47 patients reported Hispanic or Latino ethnicity, 36 identified as Black, 15 Asian, and 4 Native Hawaiian or Pacific Islander. The average age of the patient population was 44 years old (ranging from 18 to 87). Patients seen in the genetics clinic were referred for a variety of indications and included several different kidney diagnoses, including: CAKUT (n=6), tubulointerstitial disease (n=26), suspected or clinical diagnosis of a collagenopathy (n=38), focal segmental glomerulosclerosis (FSGS) (n=28), tubulopathy or electrolyte disorder (n=16), cystic kidney disease (including PKD) (n=24), hematuria and/or proteinuria (n=31), complement dysregulation (n=8), tumor or cancer (n=4), and CKD of unknown etiology (n=23). Six patients had a known genetic diagnosis, and 23 were healthy relatives of individuals with a known genetic diagnosis or potential kidney donors. Of patients seen in the kidney genetics clinic, 42% reported a family history of CKD or a personal or family history of a genetic diagnosis. A total of 186 clinical genetic tests were ordered on 174 patients;nine tests still have results pending, and ten were canceled. Genetic tests that were ordered included: small (>50) and large gene panels (n=146), exome sequencing (n=6), microarrays (n=4), and single gene and targeted variant testing (n=20). In patients that did not undergo genetic testing, reasons included: not clinically indicated, testing already ordered, and financial concerns. A diagnostic or candidate diagnostic positive result was reported in 29% of patients, involving 18 different genes. Pathogenic or likely pathogenic variants were most common in COL4A4 (n=11), followed by PKD1 (n=8). Similarly, the highest diagnostic yield was in patients with a referral ndication of a suspected collagenopathy (diagnosis in 50%) or cystic disease (diagnosis in 50%). A non-diagnostic positive finding was identified in 9% of patients and included results such as secondary findings (n=1), carrier status (n=5), and risk factors, such as an APOL1 high-risk genotype (n=9). The identification of a genetic diagnosis in patients impacted several areas of clinical care, including referrals to specialists, kidney donor selection, clinical trial eligibility (for example, in patients with a genetic Alport diagnosis), and increased access to medications (such as tolvaptan in patients with PKD1 variants). In addition, those with non-diagnostic findings were referred to ongoing research studies at the medical center to elucidate the genetics of kidney disease. Conclusion: Here, we describe the successful creation and implementation of an adult kidney genetics clinic at a large medical center. By utilizing a combination of in-person appointments and telemedicine, the clinic was able to provide access to genomic services across a broad geographic region and to a diverse patient population of adults with kidney disease. Genetic education efforts were an integral component of the clinic's success, as it increased visibility and helped providers identify patients who would benefit from genetic services, as evidenced by the high percentage of referred patients scheduling appointments and high diagnostic yield in patients undergoing testing. Identifying genetic diagnoses in this patient population has several clinical implications, including changes in management, eligibility for genetically stratified clinical trials, and treatment decisions. Continued and ongoing access to genomic services is a fundamental component of patient care in adults with kidney disease.