Application of Total Kidney Volume and Its Predictive Value in Assessment of Kidney Transplant Waitlist Candidates With Autosomal Dominant Polycystic Kidney Disease

2020 ◽  
Vol 52 (8) ◽  
pp. 2273-2277
Author(s):  
Ewa Banach-Ambroziak ◽  
Magdalena Jankowska ◽  
Małgorzata Grzywińska ◽  
Edyta Szurowska ◽  
Alicja Dębska-Ślizień
Author(s):  
Satoru Muto ◽  
Tadashi Okada ◽  
Yoshiyuki Shibasaki ◽  
Tatsuki Ibuki ◽  
Shigeo Horie

Abstract Background Autosomal dominant polycystic kidney disease (ADPKD) is a progressive condition that eventually leads to end-stage renal disease. A phase 3 trial of tolvaptan (TEMPO 3:4; NCT00428948) and its open-label extension (TEMPO Extension Japan: TEMPO-EXTJ; NCT01280721) were conducted in patients with ADPKD. In this post hoc analysis, effects on renal function and the safety profile of tolvaptan were assessed over a long-term period that included the 3-year TEMPO 3:4 and the approximately 3-year TEMPO-EXTJ trials. Methods Patients from Japanese trial sites who completed TEMPO 3:4 were offered participation in TEMPO-EXTJ. Patients whose efficacy parameters were measured at year 2 in TEMPO-EXTJ for efficacy evaluation were included. The annual slope of the estimated glomerular filtration rate (eGFR) and growth in total kidney volume (TKV) were analyzed. Results In patients who received tolvaptan in TEMPO 3:4 and TEMPO-EXTJ, the annual slope of eGFR (mL/min/1.73 m2) was − 3.480 in TEMPO 3:4 and − 3.417 in TEMPO-EXTJ, with no apparent effect of an approximately 3.6-month off-treatment interval between the two trials. In patients who received a placebo in TEMPO 3:4 before initiating tolvaptan in TEMPO-EXTJ, the slope of eGFR was significantly less steep from TEMPO 3:4 (− 4.287) to TEMPO-EXTJ (− 3.364), a difference of 0.923 (P = 0.0441). Conclusion The TEMPO-EXTJ trial supports a sustained beneficial effect of tolvaptan on eGFR. In patients who received a placebo in TEMPO 3:4, initiation of tolvaptan in TEMPO-EXTJ was associated with a significant slowing of eGFR decline.


2020 ◽  
Vol 6 (6) ◽  
pp. 407-413
Author(s):  
Cheng Xue ◽  
Li-Ming Zhang ◽  
Chenchen Zhou ◽  
Chang-Lin Mei ◽  
Sheng-Qiang Yu

<b><i>Background:</i></b> Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary nephropathy with few treatments to slow renal progression. The evidence on the effect of lipid-lowering agents (statins) on ADPKD progression remains inconclusive. <b><i>Methods:</i></b> We performed a systematic review and meta-analysis by searching the PubMed, Embase, Web of Science, and Cochrane databases (up to November 2019). Changes in estimated glomerular filtration rate (eGFR) and total kidney volume (TKV) were the primary outcomes. Mean differences (MDs) for continuous outcomes and 95% confidence intervals (CIs) were calculated by a random-effects model. <b><i>Results:</i></b> Five clinical studies with 648 participants were included. Statins did not show significant benefits in the yearly change in eGFR (4 studies, MD = −0.13 mL/min/m<sup>2</sup>, 95% CI: −0.78 to 0.52, <i>p</i> = 0.70) and the yearly change in TKV (3 studies, MD = −1.17%, 95% CI: −3.40 to 1.05, <i>p</i> = 0.30) compared with the control group. However, statins significantly decreased urinary protein excretion (−0.10 g/day, 95% CI: −0.16 to -0.03, <i>p</i> = 0.004) and serum low-density lipoprotein level (−0.34 mmol/L, 95% CI: −0.58 to −0.10, <i>p</i> = 0.006). <b><i>Conclusion:</i></b> Despite these proteinuria and lipid-lowering benefits, the effect of statins on ADPKD progression was uncertain.


2018 ◽  
Vol 13 (11) ◽  
pp. 1765-1776 ◽  
Author(s):  
Fouad T. Chebib ◽  
Vicente E. Torres

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.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Hiroki Nomi ◽  
Daisuke Mori ◽  
Shinjiro Tamai ◽  
Maho Tokuchi ◽  
Natsumi Inoue ◽  
...  

Abstract Background and Aims Tolvaptan (TV) slows down the increase in total kidney volume (TKV) in patients with autosomal dominant polycystic kidney disease (ADPKD). The efficacy of TV in patients with moderate-to-severe renal dysfunction (RD) in ADPKD remains unknown. Method This was a single-centre retrospective study involving 27 patients with ADPKD who took TV and visited our hospital in the past six years. The participants were divided into two groups: the normal-to-mild RD (estimated glomerular filtration rate (eGFR) ≥ 45mL/min/1.73m2) group and the moderate-to-severe RD (eGFR &lt; 45mL/min/1.73m2) group. Treatment effects were evaluated using ΔTKV, which was calculated as post-/pre-treatment annual TKV change. Continuous variables are presented using the median [interquartile range]. Results The moderate-to-severe RD group comprised 11 patients. Baseline characteristics of the normal-to-mild vs. moderate-to-severe RD group were as follows: eGFR, 56 [50–69] vs. 29 [24–38] mL/min/1.73m2; age, 48 [39–55] vs. 49 [43–58] years; male gender, 57% vs. 36%; body mass index (BMI) , 26 [23–28] vs. 24 [22–27] kg/m2; TKV 1700 [1084–2574] vs. 1827 [1331–2424] mL; family history of ADPKD, 100% vs. 82%; history of cerebral aneurysm, 19% vs. 36%; hypertension, 81% vs. 82%; hyperuricemia, 13% vs. 27%; dyslipidaemia, 19% vs. 18%; diabetes, 6.1% vs. 9.1% and systolic blood pressure (sBP) on admission 138 [129–144] vs. 131 [128-137] mmHg. No significant differences were noted in all these parameters, except for renal function. The starting dose of TV was 60 mg/day in all cases (0.9 [0.7–1.0] vs. 0.9 [0.8–1.1] mg/kg; P = 0.35). Urine volume (7.5 [5.7–9.6] vs. 4.0 [3.3–4.7] L/day; P = 0.006) and urinary sodium excretion (163 [126–226] vs. 89 [81–120] mEq/day; P = 0.003) were higher in the normal-to-mild RD group. Between the groups, there were no differences in urine protein (0.12 [0.0–0.3] vs. 0.16 [0.08–0.29] g/day; P = 0.31) and ΔeGFR (98% [88–123] vs. 106% [102–112]; P = 0.45), which was calculated as post-/pre-treatment annual eGFR change. Although both groups experienced the therapeutic effects of TV, the efficacy was poorer in the moderate-to-severe RD group (ΔTKV, 82% [76–85] vs. 96% [86–97]; P = 0.001). Conclusion The efficacy of TV patients with moderate-to-severe RD in ADPKD might be modest.


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