Tolvaptan Therapy Research Articles

Tolvaptan therapy for edema in patients with chronic kidney disease.

Tolvaptan is a vasopressin V2 receptor antagonist that is commonly prescribed to alleviate edema associated with renal diseases. However, the clinical benefits of tolvaptan in chronic kidney disease (CKD) remain unclear. This study aimed to evaluate the effectiveness of tolvaptan in managing edema caused by CKD. The efficacy and treatment regimen of tolvaptan were assessed in a cohort of 96 patients with renal edema and CKD. During the treatment, the patients' creatinine (CR), uric acid (UA), and estimated glomerular filtration rate (eGFR) were monitored as important indicators of kidney function. Coagulation-associated molecules including fibrinogen, D-dimer, and fibrin degradation products (FDPs) were measured. Electrolyte disorders and acute kidney injury were closely monitored. Tolvaptan was administered at a daily dose of 7.5 mg, and 30 mg of edoxaban was administered to manage deep vein thrombosis. During the course of tolvaptan therapy, the eGFR of the patients was not declined. Edema was eliminated in 82.18% of patients. Proteinuria was reduced in the patients (p<0.05). There were no significant changes in serum sodium levels throughout treatment, and no significant difference was observed in blood volume between the end of treatment and baseline levels. Importantly, acute kidney injury did not occur, and renal edema and deep vein thrombosis were successfully treated. As long as a rational treatment regimen is followed, tolvaptan is a safe and effective diuretic for treating edema in CKD, even in the late stages of CKD without reducing residual renal function in the patients.

#1636 Treatment of Tolvaptan related polyuria with bendroflumethiazide for ADPKD: Does it really work?

Abstract Background and Aims Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disease worldwide and accounts for 10% of patients on renal replacement therapy. Currently, the arginine vasopressin (AVP) V2 receptor antagonist Tolvaptan is the only available treatment for ADPKD which slows cyst formation and thus the progression of kidney disease by inducing AVP resistance. However, its aquaretic side effects can be debilitating and is the most common reason for medication discontinuation. Thiazides such as bendroflumethiazide are natriuresis-promoting diuretics through their action on the sodium-chloride channel in the distal convoluted tubule that are widely used to treat polyuria in inherited AVP deficiency or resistance. However, there is limited information about their effect in patients treated with Tolvaptan. The aim of this observational study is to review the impact on patients’ quality of life by using a low dose bendroflumethiazide with Tolvaptan in patients with ADPKD who are suffering from Tolvaptan induced aquaretic side effects. Method Details of all patients with ADPKD who are on Tolvaptan with or without bendroflumethiazide who are currently attending the polycystic kidney disease (PKD) clinic at Royal Free London NHS Foundation Trust were obtained, and their medications reviewed. Patients who have previously been or were currently on bendroflumethiazide to enable them to continue Tolvaptan therapy were identified. Information about the impact of bendroflumethiazide on their quality of life and their aquaretic side effects were obtained via phone call. If they discontinued bendroflumethiazide, the reason for this was explored. In addition, eGFR, sodium, potassium, and calcium at the time of bendroflumethiazide initiation as well as at three, six, nine and twelve months post bendroflumethiazide initiation were obtained. Results Out of 136 patients receiving Tolvaptan for treatment of ADPKD at our centre, eight (5.8%) were prescribed bendroflumethiazide for treatment of their aquaretic side effects from Tolvaptan. Two of these eight patients (25%) stopped bendroflumethiazide due to adverse reactions. The remaining six patients (75%) remained on the medication, and all reported significant subjective improvement in their symptoms of polyuria, nocturia and in their overall quality of life. Two of the six patients (33.3%) that remained on bendroflumethiazide had also subsequently increased their Tolvaptan dose. No electrolyte disturbances were noted after initiation of bendroflumethiazide. Conclusion Using bendroflumethiazide appears to improve the quality of life through reduction of polyuria and nocturia in patients suffering from Tolvaptan-induced aquaretic side effects with some patients subsequently able to increase their Tolvaptan dose by taking bendroflumethiazide which might result in augmented therapeutic benefit of Tolvaptan. Further placebo-controlled randomised studies with longitudinal will be needed to determine the true benefit-disbenefit balance of thiazide therapy in patients taking tolvaptan, especially to determine whether there is a negative effect on efficacy of tolvaptan on the underlying ADPKD. However, based on our small observational study, the number of patients needed to determine whether bendroflumethiazide improves the tolerability and medication adherence in patients who are debilitated by the aquaretic side effects of Tolvaptan would be small.

#2119 Long-term efficacy of tolvaptan therapy in patients with ADPKD

Abstract Background and Aims Currently, the only available therapy to ameliorate disease progression in patients with autosomal dominant polycystic kidney disease (ADPKD) is tolvaptan, a vasopressin V2 receptor antagonist. Real-life data on tolvaptan treatment effect is sparce, with several limitations including restricted follow-up, relatively small patient groups, no control groups, or only data reported on kidney function without total kidney volume. We studied, therefore, the long-term effect of tolvaptan on kidney function as well as kidney growth in a relatively large number of real-life ADPKD patients and controls. Moreover, we investigated the effect of salt and protein intake on long-term treatment efficacy. Method Data from two national ADPKD cohorts were pooled. Kidney function (creatinine-based eGFR) was measured at least yearly and total kidney volume (TKV, measured by MRI or CT) at least 3-yearly. Salt and protein intake were measured by 24 h urine excretion. To investigate the long-term effects of tolvaptan we assessed change in eGFR and TKV before as well as after start of tolvaptan using linear mixed effects models. For this purpose, we excluded the acute treatment effect from start to 6 months after initiation of tolvaptan. As a control group, we included all patients who were not treated with tolvaptan, assessing change in eGFR and TKV before and after the theoretical start of treatment (based on the average time of tolvaptan initiation observed in the tolvaptan-treated group) as well as a matched control group. Subgroup analyses of salt and protein intake were based on the median urinary excretion of sodium or urea. Results 697 patients (47 ± 12 years, 59.1% female) were included, of which 104 patients used tolvaptan. Mean duration of tolvaptan use was 6.0 ± 4.5 years (range: 0.8 to 15.6). Tolvaptan use reduced yearly eGFR decline by 17.4% (−4.43 to −3.66 mL/min/1.73 m2/year, p = 0.03, number of measurements: n = 817), whereas in the non-tolvaptan control group after the theoretical start of treatment, eGFR decline increased by 13.3% (−1.95 to −2.21 mL/min/1.73 m2/year, p = 0.2, n = 2804). Long-term TKV growth did not change after start of tolvaptan treatment (4.90 to 5.53%/year, p = 0.5, n = 316). Similar results were obtained in the matched control group. A more substantial treatment effect of tolvaptan on eGFR slope was noted in patients with high compared to low salt intake (assessed as ≥ versus &amp;lt; median urinary sodium excretion of 146 mmol/24 h (difference 1.62 (0.22 to 3.02) mL/min/1.73 m2/year, p = 0.02). Subgroup analysis according to median protein intake did not show a significant difference in tolvaptan treatment effect. Conclusion In this study, with real-life patient data, long-term follow-up, and a control group, we found that tolvaptan attenuated long-term kidney function decline but, notably, did not influence kidney growth. Higher daily salt intake was associated with a more substantial tolvaptan treatment effect, perhaps due to higher vasopressin levels before treatment, and consequently more vasopressin antagonism by tolvaptan.

Measured and Estimated Glomerular Filtration Rate to Evaluate Rapid Progression and Changes over Time in Autosomal Polycystic Kidney Disease: Potential Impact on Therapeutic Decision-Making.

Autosomal polycystic kidney disease (ADPKD) is the most common genetic form of kidney failure, reflecting unmet needs in management. Prescription of the only approved treatment (tolvaptan) is limited to persons with rapidly progressing ADPKD. Rapid progression may be diagnosed by assessing glomerular filtration rate (GFR) decline, usually estimated (eGFR) from equations based on serum creatinine (eGFRcr) or cystatin-C (eGFRcys). We have assessed the concordance between eGFR decline and identification of rapid progression (rapid eGFR loss), and measured GFR (mGFR) declines (rapid mGFR loss) using iohexol clearance in 140 adults with ADPKD with ≥3 mGFR and eGFRcr assessments, of which 97 also had eGFRcys assessments. The agreement between mGFR and eGFR decline was poor: mean concordance correlation coefficients (CCCs) between the method declines were low (0.661, range 0.628 to 0.713), and Bland and Altman limits of agreement between eGFR and mGFR declines were wide. CCC was lower for eGFRcys. From a practical point of view, creatinine-based formulas failed to detect rapid mGFR loss (-3 mL/min/y or faster) in around 37% of the cases. Moreover, formulas falsely indicated around 40% of the cases with moderate or stable decline as rapid progressors. The reliability of formulas in detecting real mGFR decline was lower in the non-rapid-progressors group with respect to that in rapid-progressor patients. The performance of eGFRcys and eGFRcr-cys equations was even worse. In conclusion, eGFR decline may misrepresent mGFR decline in ADPKD in a significant percentage of patients, potentially misclassifying them as progressors or non-progressors and impacting decisions of initiation of tolvaptan therapy.

Real-life use of tolvaptan in ADPKD: a retrospective analysis of a large Canadian cohort

Tolvaptan is the first disease-modifying drug proven to slow eGFR decline in high-risk patients with ADPKD. However, barriers from the patient perspective to its use in real-life settings have not been systemically examined in a large cohort. This was a single-center, retrospective study of 523 existing or new patients with ADPKD followed at the Center for Innovative Management of PKD in Toronto, Ontario, between January 1, 2016 to December 31, 2018. All patients underwent clinical assessment including total kidney volume measurements and Mayo Clinic Imaging Class (MCIC). Those who were deemed to be at high risk were offered tolvaptan with their preference (yes or no) and reasons for their choices recorded. Overall, 315/523 (60%) patients had MCIC 1C-1E; however, only 96 (30%) of them were treated with tolvaptan at their last follow-up. Among these high-risk patients, those not treated versus treated with tolvaptan were more likely to have a higher eGFR (82 ± 26 vs. 61 ± 27 ml/min/1.73 m2), CKD stages 1–2 (79% vs. 41%), and MCIC 1C (63% vs. 31%). The most common reasons provided for not taking tolvaptan were lifestyle preference related to the aquaretic effect (51%), older age ≥ 60 (12%), and pregnancy/family planning (6%). In this real-world experience, at least 60% of patients with ADPKD considered to be at high risk for progression to ESKD by imaging were not treated with tolvaptan; most of them had early stages of CKD with well-preserved eGFR and as such, were prime targets for tolvaptan therapy to slow disease progression. Given that the most common reason for tolvaptan refusal was the concern for intolerability of the aquaretic side-effect, strategies to mitigate this may help to reduce this barrier to tolvaptan therapy.

Plasma copeptin concentration is a predictor of tolvaptan efficacy in patients with hepatic ascites

AbstractAimsNo solid evidence‐based opinion was raised regarding predictors of the degree of ascites reduction with tolvaptan. This retrospective cohort study aimed to examine whether serum copeptin concentration is a useful predictor of this.MethodsThe study population consisted of 80 patients with liver cirrhosis treated with tolvaptan for hepatic ascites effusions at Nara Medical University Hospital from May 2014 to December 2018. Forty‐three patients who lost &gt;1.5 kg of body weight in the first week after starting tolvaptan were classified as good responders and the remaining 37 as poor responders. Various laboratory parameters were measured immediately before the start of tolvaptan therapy to examine factors associated with predicting its efficacy.ResultsIn the univariate analysis, no significant differences with respect to age (67.6 vs. 69.8 years, p &gt; 0.05), sex, body mass index (24.8 vs. 23.7 kg/m2, p &gt; 0.05), Child–Pugh score (9.4 vs. 9.7, p &gt; 0.05), and Model for End‐stage Liver Disease score (11 vs. 12, p &gt; 0.05) were found between the two groups. Conversely, aspartate transferase and alanine transaminase (ALT) levels were significantly lower in the good response group (52.9 ± 56.3 vs. 68.8 ± 50.7 U/L, p &lt; 0.05; 26.2 ± 30.6 vs. 40.5 ± 33.5 U/L, p &lt; 0.01), whereas serum copeptin and serum sodium concentrations were significantly higher (57.1 ± 15.0 vs. 45.8 ± 16.0 pg/mL, p &lt; 0.01; 136.3 ± 3.4 vs. 133.8 ± 5.8 mEq/L, p &lt; 0.05). In the multivariate analysis, serum copeptin concentration and ALT were statistically significant factors (p &lt; 0.01, p &lt; 0.05). Regression analysis of the association between the tolvaptan efficacy for refractory ascites and pretreatment serum copeptin concentration showed that a copeptin concentration cutoff of 45.9 pg/mL could predict treatment efficacy with a sensitivity, specificity, and area under the curve of 76.7%, 59.5%, and 0.71%, respectively.ConclusionSerum copeptin concentration may be a predictor of tolvaptan efficacy for refractory ascites effusion in Japanese patients with liver cirrhosis.

Are you ready to accompany autosomal dominant polycystic kidney disease patients in their treatment journey? Real practice for selecting rapid progressors and treatment with tolvaptan

Tolvaptan treatment is costly, often accompanied by aquaresis-related adverse events, and requires careful monitoring by medical staff due to the possibility of hepatotoxicity. Nevertheless, it is the only disease-modifying drug to date that has been shown to successfully delay renal replacement therapy. For more patients to receive proper treatment, medical doctors, the rest of the medical team, and the patient must all work together. This paper reviews parameters that can help identify rapid autosomal dominant polycystic kidney disease progressors, who are the target of tolvaptan therapy. It is expected that these parameters will help nephrologists learn practical prescription methods and identify patients who can benefit from tolvaptan treatment. Although several strategies can be used to find rapid progressors, the present review focuses on a practical method to identify rapid progressors according to the presence or absence of evidence and the factors associated with rapid progression based on the Mayo image classification.

Public support for patients with intractable diseases in Japan: impact on clinical indicators from nationwide registries in patients with autosomal dominant polycystic kidney disease.

Clinical practice guidelines recommend antihypertensive and tolvaptan therapies for patients with autosomal dominant polycystic kidney disease (ADPKD) in Japan. However, tolvaptan therapy may pose an economic burden. The Japanese Ministry of Health, Labour and Welfare supports patients with intractable diseases. This study aimed to confirm the impact of the intractable disease system in Japan on the clinical treatment of ADPKD. We analyzed the data of 3768 patients with ADPKD having a medical subsidy certificate from the Japanese Ministry of Health, Labour and Welfare in 2015-2016. The following quality indicators were use: the adherence rate to the 2014 clinical practice guideline for polycystic kidney disease (prescription rates of antihypertensive agents and tolvaptan in this cohort) and the number of Japanese patients with ADPKD nationwide started on renal replacement therapy in 2014 and 2020. Compared with new applications from 2015 to 2016, the prescription rates of antihypertensives and tolvaptan for the indicated patients at the 2017 renewal application increased by 2.0% (odds ratio = 1.41, p = 0.008) and 47.4% (odds ratio = 10.1, p > 0.001), respectively. These quality indicators improved with antihypertensive treatment, especially in patients with chronic kidney disease stages 1-2 (odds ratio = 1.79, p = 0.013) and in those aged < 50years (odds ratio = 1.70, p = 0.003). The number of patients with ADPKD who were started on renal replacement therapy in Japan decreased from 999 in 2014 to 884 in 2020 in the nationwide database (odds ratio = 0.83, p < 0.001). The Japanese public intractable disease support system contributes to improvement of ADPKD treatment.

#5783 REAL-LIFE USE OF TOLVAPTAN IN ADPKD: A RETROSPECTIVE ANALYSIS OF A LARGE CANADIAN COHORT

Abstract Background and Aims Tolvaptan is the first disease-modifier therapy proven to slow eGFR decline in high-risk patients with ADPKD. However, barriers to its use in real-life settings have not been examined. Method Single-center, retrospective study of 523 current or new patients with ADPKD followed at the Center for Innovative Management of PKD in Toronto, Ontario between January 1, 2016 to December 30, 2018. All patients had clinical assessment and total kidney volume measurements; those deemed to be at high risk based on their Mayo Clinic Imaging Class (MCIC) 1C, 1D, or 1E, were offered tolvaptan with their preference (yes or no) and reasons for their choices recorded. Results Overall, 315/523 (60.2%) patients had MCIC 1C-1E; however, only 96 (30%) of them were treated with tolvaptan at the last follow-up. Among these high-risk patients, those treated with tolvaptan were more likely to have a higher eGFR (61 ±27 vs. 82 ±26 ml/min/1.73 m2), CKD stages 1–2 (41% vs. 79%), and MCIC 1D-1E (69% vs. 37%). The most common reasons provided for not taking tolvaptan were lifestyle preference related to the aquaretic effect (51%), older age ≥60 (12%), and pregnancy or family planning (6%). Conclusion In this real-world experience, at least 60% of patients with ADPKD considered to be at high risk for progression to ESKD by imaging were not treated with tolvaptan; most of them had earlier stages of CKD with well-preserved eGFR. The most common reason for their refusal to consider tolvaptan is a concern for intolerability of the aquaretic side-effect; strategies to mitigate this side-effect may help to reduce the barrier to tolvaptan therapy.

Sodium evolution in hyponatraemia: a mixed effects model analysis of the Hyponatraemia Registry.

Achieving recommended targets of sodium correction is challenging to physicians treating hyponatraemia. Plasma sodium has to be increased effectively, yet overcorrection must be prevented. This is often hampered by a high variability of responses to treatment. Here, we sought to delineate factors influencing sodium evolution. We retrospectively analysed 3460 patients from the multinational Hyponatraemia Registry comprising a wide range of hyponatraemia aetiologies and treatment strategies. Multivariable linear mixed effects models were applied to identify predictors of plasma sodium evolution within the first 24 h of treatment. Evolution of sodium levels over time showed a curvilinear pattern with steeper rise at earlier time points. Baseline sodium showed the most pronounced impact with an additional increment of 3.12 mEq/L for every 10 mEq/L initial sodium reduction. With sodium increments of 1.9 mEq/L and 1.4 mEq/L per 24 h, respectively, the entities hypovolaemic and thiazide-associated hyponatraemia were independent factors for sodium evolution. Therapeutic regimens using hypertonic saline (4.6 mEq/L/24 h), tolvaptan (3.4 mEq/L/24 h), or combination therapy (2.6 mEq/L/24 h) were also associated with a significantly larger sodium rise when compared with no active treatment. Choice and dosing of active hyponatraemia therapy should be adjusted not only according to aetiology but most importantly to pretreatment sodium. Although counterintuitive, less aggressive therapy in more profound hyponatraemia might be safer but yet effective at least in less severe cases.

First reports of clinical effects of transjugular intrahepatic portosystemic shunt in four patients with cirrhotic ascites refractory to tolvaptan

ObjectiveAscites in patients with decompensated cirrhosis can lead to abdominal distention and decrease quality of life. Tolvaptan, a vasopressin V2 receptor antagonist, is an effective agent in the treatment of...

Optimal Patient Selection and Treatment Timing for Tolvaptan Therapy Following Cardiovascular Surgery - Reply.

Optimal Patient Selection and Treatment Timing for Tolvaptan Therapy Following Cardiovascular Surgery - Reply.

Optimal Patient Selection and Treatment Timing for Tolvaptan Therapy Following Cardiovascular Surgery.

Optimal Patient Selection and Treatment Timing for Tolvaptan Therapy Following Cardiovascular Surgery.

Preclinical evaluation of tolvaptan and salsalate combination therapy in a Pkd1-mouse model.

Background: Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic disorder and an important cause of end stage renal disease (ESRD). Tolvaptan (a V2R antagonist) is the first disease modifier drug for treatment of ADPKD, but also causes severe polyuria. AMPK activators have been shown to attenuate cystic kidney disease. Methods: In this study, we tested the efficacy of the combined administration of salsalate (a direct AMPK activator) and tolvaptan using clinically relevant doses in an adult-onset conditional Pkd1 knock-out (KO) mouse model. Results: Compared to untreated Pkd1 mutant mice, the therapeutic effects of salsalate were similar to that of tolvaptan. The combined treatment tended to be more effective than individual drugs used alone, and was associated with improved kidney survival (p < 0.0001) and reduced kidney weight to body weight ratio (p < 0.0001), cystic index (p < 0.001) and blood urea levels (p < 0.001) compared to untreated animals, although the difference between combination and single treatments was not statistically significant. Gene expression profiling and protein expression and phosphorylation analyses support the mild beneficial effects of co-treatment, and showed that tolvaptan and salsalate cooperatively attenuated kidney injury, cell proliferation, cell cycle progression, inflammation and fibrosis, and improving mitochondrial health, and cellular antioxidant response. Conclusion: These data suggest that salsalate-tolvaptan combination, if confirmed in clinical testing, might represent a promising therapeutic strategy in the treatment of ADPKD.

PS-C26-10: THE PROPKD SCORE IS ASSOCIATED WITH THE PROGRESSION OF RENAL INVOLVEMENT IN PATIENTS WITH POLYCYSTIC KIDNEY DISEASE TREATED WITH TOLVAPTAN

Background: The PROPKD score has been proposed to evaluate the risk of the progression to end stage renal failure in patients with autosomal dominant polycystic kidney disease (ADPKD), based on gender (male: 1point), hypertension under 35 years old (2 points), urological event under 35 years old (2 points), and gene mutation (PKD1 truncating mutation: 4 points, PKD1 non-truncating mutation: 2 points, PKD2: 0 point). Although tolvaptan has benefits for renal involvement, whether PROPKD score could predict future renal involvement in patients with ADPKD treated with tolvaptan is unknown. Thus, we explored the effects of tolvaptan on the annual changes in total kidney volume (%TKV) and estimated glomerular filtration rate (%eGFR) according to the PROPKD score in these patients. Methods: 32 ADPKD patients treated tolvaptan for at least a year were retrospectively analyzed (the mean observation period: 3.6 years). We examined the decline in renal function, %TKV by computed tomography, and gene mutation. The association between %eGFR and %TKV change before and after tolvaptan treatment, annual TKV change (%TKV) and PROPKD score was analyzed. Results: We identified gene mutations in ADPKD patients: PKD1 truncating mutation (n = 15), PKD1 non-truncating mutation (n = 5), PKD2 mutation (n = 6), and mutation not found (n = 6). Mean %TKV and eGFR were 1843 ± 986 ml and 54.7 ± 21.0 ml/min/1.73 m2, respectively. The mean PROPKD score was 3.3 ± 2.4 points and showed a significant negative correlation with %eGFR before and after tolvaptan treatment (p = 0.044/0.016), and no significant correlation with %TKV before and after tolvaptan treatment. Conclusion: The higher PROPKD score, the faster the decrease in %eGFR during tolvaptan therapy, suggesting that the PROPKD score may be useful as a predictor of the risk of progression to renal failure after tolvaptan introduction.

Utility of ultrasonography for predicting indications for tolvaptan in patients with autosomal dominant polycystic kidney disease

PurposeTolvaptan is the first approved treatment for autosomal dominant polycystic kidney disease (ADPKD) that targets a mechanism directly contributing to the development and growth of renal cysts. We investigated the ability of ultrasonography to predict total kidney volume (TKV) of 750 mL or more, which is an indication for tolvaptan therapy in patients with ADPKD.MethodsA total of 46 patients with ADPKD were evaluated. The most statistically appropriate measurement based on ultrasonography for predicting TKV determined by computed tomography (CT) was assessed.ResultsTKV determined by CT was 796.8 (508.8–1,560.3) mL. The median length, anteroposterior distance, and mediolateral distance determined using ultrasonography were 15.7 cm, 7.6 cm, and 7.6 cm in the left kidney, and 13.4 cm, 6.9 cm, and 7.2 cm in the right kidney, respectively. Multivariate regression analysis showed that total kidney length (left and right) [variance inflation factor (VIF), 9.349] and total mediolateral distance (left and right) (VIF, 3.988) were independently associated with TKV. The correlation (r) between the logarithm of TKV determined by CT and total mediolateral distance determined using ultrasonography was 0.915 (p < 0.001). The linear regression equation was log (total kidney volume) = 1.833 + 0.075 × total mediolateral distance (left and right) based on ultrasonography. The area under the receiver operating characteristic curve for total mediolateral distance determined using ultrasonography to predict TKV of 750 mL or more was 0.989. Using the total mediolateral distance cut-off value of 14.2 cm, the sensitivity and specificity were 96.0% and 100.0%, respectively.ConclusionTotal mediolateral distance determined using ultrasonography can predict TKV in patients with ADPKD.

Outcomes from the Northeast England cohort of autosomal dominant polycystic kidney disease (ADPKD) patients on tolvaptan.

Autosomal dominant polycystic kidney disease (ADPKD) is a cause of end-stage kidney disease (ESKD). The vasopressin V2-receptor antagonist tolvaptan has been shown within randomized clinical trials to slow down decline of kidney function in patients with ADPKD at risk of rapid progression. We performed a retrospective review of a Northeast England cohort of adult ADPKD patients who had been established on tolvaptan therapy to determine its efficacy in a real-world clinic setting. Other inclusion criteria involved a pre-treatment decline in greater than 2.5 ml/min/1.73m2/year based on readings for a 3 year period, and ability to tolerate and maintain tolvaptan treatment for at least 12 months. We calculated based on eGFR slopes, predicted time to reach ESKD with and without tolvaptan therapy. The cohort of patients included 21 from the Northeast of England. The mean rate of eGFR decline prior to treatment was -6.02 ml/min/1.73m2/year for the cohort. Following tolvaptan treatment, the average decline in eGFR was reduced to -2.47 ml/min/1.73m2/year, gaining a mean 8 years and 4 months delay to reach ESKD. The majority of patients (n=19) received and tolerated full dose tolvaptan (90 mg/30 mg). The real-life use of tolvaptan gave a dramatic improvement in eGFR slopes, much more than previously reported in clinical studies. These effects may be in part due to careful patient identification, selection and inclusion of patients who were able to tolerate tolvaptan therapy, excellent compliance with medication and a "tolvaptan clinic" effect where great personal care was given to these patients.

Efficacy and safety of tolvaptan in chronic heart failure

AbstractBackgroundThe efficacy and safety of tolvaptan (TLV) in patients with chronic heart failure (CHF) are unclear.AimThe aim of this study was to evaluate the efficacy and safety of tolvaptan (TLV) versus conventional therapy, primarily furosemide (FRM). In addition, the effect of the nutritional status on the efficacy of TLV was evaluated.MethodThis retrospective study included patients with CHF who were hospitalised and treated between March 2015 and February 2019, including 51 patients in the FRM group and 63 patients in the TLV group.ResultWeight loss did not differ between the FRM and TLV groups (−2.1 ± 2.1 kg vs −1.5 ± 3.5 kg, p = 0.250). After 7 days, the change in the estimated glomerular filtration rate was significantly smaller in the FRM group (56.5 ± 22.2 vs 51.9 ± 20.0 mL/min/1.73 m2, p = 0.002). There was no significant difference in serum sodium (Na) levels between days 0 and 7 in the FRM group (138.8 ± 5.2 vs 139.2 ± 3.9 mEq/L, p = 0.487). However, the serum Na level was significantly increased in the TLV group (138.4 ± 5.0 mEq/L vs 139.4 ± 4.0 mEq/L, p = 0.047). There was no significant correlation between weight loss due to diuresis and the objective prognostic nutritional index in either group.ConclusionIn hyponatremic patients with CHF, TLV may be more effective than FRM in slowing the course of renal damage and elevating serum Na levels; however, nutritional indices may not be necessary to consider while administering TLV.

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

Background and objectiveAutosomal-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.MethodsThis 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.ResultsOur 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).ConclusionDietary 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.

Long-term Tolvaptan therapy in the treatment of SIAD in Elderly- A case report with challenging cytochrome P 450 drug interactions

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)