Safety and efficacy of long-acting somatostatin treatment in autosomal-dominant polycystic kidney disease

Ruggenenti, Piero; Remuzzi, Andrea; Ondei, Patrizia; Fasolini, Giorgio; Antiga, Luca; Ene-Iordache, Bogdan; Remuzzi, Giuseppe; Epstein, Franklin H.

doi:10.1111/j.1523-1755.2005.00395.x

Cited by 244 publications

(224 citation statements)

References 37 publications

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“…Another clinical trial run in parallel with and independent of the study presented here found that a treatment period of the same duration (6 months) with another long-acting somatostatin analogue (lanreotide) achieved a reduction of liver volume in patients with autosomal-dominant polycystic liver disease or AD-PKD (15) similar to the reduction we observed in ADPKD patients. Finding that lanreotide also limited the growth of kidney volumes in the subgroup of patients with ADPKD confirmed and extended our previous data that the growth of ADPKD kidneys can be prevented by octreotide therapy (6).…”

Section: Discussionsupporting

confidence: 75%

“…Main patient characteristics at inclusion have been reported in detail (6). Briefly, systolic and diastolic BP averaged 144 Ϯ 12 mmHg and 94 Ϯ 12 mmHg, respectively.…”

Section: Clinical Characteristicsmentioning

confidence: 99%

“…Haplotypes were reconstructed using the Genehunter package (version 1.2). Adults with a serum creatinine concentration Ͻ3 mg/dl, but Ͼ1.2 mg/dl (men) or Ͼ1.0 mg/dl (women), and without biliary or urinary tract lithiasis at screening ultrasound evaluation were eligible for study participation (6). Those with concomitant liver or renal parenchymal disease different from polycystic disease; more than two hemorrhagic or complicated cysts; biliary or urinary tract obstruction or infection; urinary protein excretion rate Ͼ1 g/24 h or abnormal urinalysis suggestive of concomitant, clinically significant glomerular disease; diabetes, cancer, or major systemic diseases that could prevent completion of the planned follow-up or interfere with data collection or interpretation; psychiatric disorders or any condition that could prevent full comprehension of the purposes and risks of the study; and pregnant or lactating women or fertile women without effective contraception were not considered eligible for study participation.…”

Section: Patientsmentioning

confidence: 99%

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Reducing Polycystic Liver Volume in ADPKD

Caroli

Antiga²,

Cafaro

et al. 2010

Clinical Journal of the American Society of Nephrology

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137

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Background and objectives: No medical treatment is available for polycystic liver disease, a frequent manifestation of autosomal-dominant polycystic kidney disease (ADPKD). In a prospective, randomized, double-blind, crossover study, 6 months of octreotide (40 mg every 28 days) therapy limited kidney volume growth more effectively than placebo in 12 patients with ADPKD.Design, setting, participants, & measurements: In this secondary, post hoc analysis of the above study, octreotide-induced changes in liver volumes compared with placebo and the relationship between concomitant changes in liver and kidney volumes were evaluated. Those analyzing liver and kidney volumes were blinded to treatment.Results: Liver volumes significantly decreased from 1595 ؎ 478 ml to 1524 ؎ 453 ml with octreotide whereas they did not appreciably change with placebo. Changes in liver volumes were significantly different between the two treatment periods (؊71 ؎ 57 ml versus ؉14 ؎ 85 ml). Octreotide-induced liver volume reduction was fully explained by a reduction in parenchyma volume from 1506 ؎ 431 ml to 1432 ؎ 403 ml. Changes in liver volumes were significantly correlated with concomitant changes in kidney volumes (r ‫؍‬ 0.67) during octreotide but not during placebo treatment. Liver and kidney volume changes significantly differed with both treatments (octreotide: ؊71 ؎ 57 ml versus ؉71 ؎ 107; placebo: ؉14 ؎ 85 ml versus ؉162 ؎ 114), but net reductions in liver (؊85 ؎ 103 ml) and kidney (؊91 ؎ 125 ml) volume growth on octreotide versus placebo were similar.Conclusions: Octreotide therapy reduces liver volumes in patients with ADPKD and is safe.

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Section: Discussionsupporting

confidence: 75%

“…Main patient characteristics at inclusion have been reported in detail (6). Briefly, systolic and diastolic BP averaged 144 Ϯ 12 mmHg and 94 Ϯ 12 mmHg, respectively.…”

Section: Clinical Characteristicsmentioning

confidence: 99%

Section: Patientsmentioning

confidence: 99%

See 1 more Smart Citation

Reducing Polycystic Liver Volume in ADPKD

Caroli

Antiga²,

Cafaro

et al. 2010

Clinical Journal of the American Society of Nephrology

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137

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“…Four published trials examine the possible benefit of regular injection of a somatostatin analog, which aims at inhibition of cAMP production in renal cells and resultant cyst development and growth (39)(40)(41)(42). Essential data are summarized in Table 2.…”

Section: Somatostatin Analogsmentioning

confidence: 99%

“…Essential data are summarized in Table 2. Three small studies focused on polycystic liver disease and assessed effect on TKV as secondary end points; their data suggested marginal benefit on TKV (39)(40)(41). A fourth randomized controlled trial evaluated 70 ADPKD patients using octreotide over 3 years (42).…”

Section: Somatostatin Analogsmentioning

confidence: 99%

Novel Treatments of Autosomal Dominant Polycystic Kidney Disease

Mahnensmith¹

2014

Clinical Journal of the American Society of Nephrology

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Effect of Lanreotide on Kidney Function in Patients With Autosomal Dominant Polycystic Kidney Disease

Meijer

Visser

Aerts

et al. 2018

JAMA

101

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IMPORTANCE Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive cyst formation in both kidneys and loss of renal function, eventually leading to a need for kidney replacement therapy. There are limited therapeutic management options. OBJECTIVE To examine the effect of the somatostatin analogue lanreotide on the rate of kidney function loss in patients with later-stage ADPKD. DESIGN, SETTING, AND PARTICIPANTS An open-label randomized clinical trial with blinded end point assessment that included 309 patients with ADPKD from July 2012 to March 2015 at 4 nephrology outpatient clinics in the Netherlands. Eligible patients were 18 to 60 years of age and had an estimated glomerular filtration rate (eGFR) of 30 to 60 mL/min/1.73 m 2. Follow-up of the 2.5-year trial ended in August 2017. INTERVENTIONS Patients were randomized to receive either lanreotide (120 mg subcutaneously once every 4 weeks) in addition to standard care (n = 153) or standard care only (target blood pressure <140/90 mm Hg; n = 152). MAIN OUTCOMES AND MEASURES Primary outcome was annual change in eGFR assessed as slope through eGFR values during the 2.5-year treatment phase. Secondary outcomes included change in eGFR before vs after treatment, incidence of worsening kidney function (start of dialysis or 30% decrease in eGFR), change in total kidney volume and change in quality of life (range: 1 [not bothered] to 5 [extremely bothered]). RESULTS Among the 309 patients who were randomized (mean [SD] age, 48.4 [7.3] years; 53.4% women), 261 (85.6%) completed the trial. Annual rate of eGFR decline for the lanreotide vs the control group was −3.53 vs −3.46 mL/min/1.73 m 2 per year (difference, −0.08 [95% CI, −0.71 to 0.56]; P = .81). There were no significant differences for incidence of worsening kidney function (hazard ratio, 0.87 [95% CI, 0.49 to 1.52]; P = .87), change in eGFR (−3.58 vs −3.45; difference, −0.13 mL/min/1.73 m 2 per year [95% CI, −1.76 to 1.50]; P = .88), and change in quality of life (0.05 vs 0.07; difference, −0.03 units per year [95% CI, −0.13 to 0.08]; P = .67). The rate of growth in total kidney volume was lower in the lanreotide group than the control group (4.15% vs 5.56%; difference, −1.33% per year [95% CI, −2.41% to −0.24%]; P = .02). Adverse events in the lanreotide vs control group included injection site discomfort (32% vs 0.7%), injection site papule (5.9% vs 0%), loose stools (91% vs 6.6%), abdominal discomfort (79% vs 20%), and hepatic cyst infections (5.2% vs 0%). CONCLUSIONS AND RELEVANCE Among patients with later-stage autosomal dominant polycystic kidney disease, treatment with lanreotide compared with standard care did not slow the decline in kidney function over 2.5 years of follow-up. These findings do not support the use of lanreotide for treatment of later-stage autosomal dominant polycystic kidney disease.

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Safety and efficacy of long-acting somatostatin treatment in autosomal-dominant polycystic kidney disease

Cited by 244 publications

References 37 publications

Reducing Polycystic Liver Volume in ADPKD

Reducing Polycystic Liver Volume in ADPKD

Novel Treatments of Autosomal Dominant Polycystic Kidney Disease

Effect of Lanreotide on Kidney Function in Patients With Autosomal Dominant Polycystic Kidney Disease

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