Which therapies are the most effective to prevent the progression of autosomal dominant polycystic kidney disease?

Current clinical care for people who have autosomal dominant polycystic kidney disease (ADPKD) focuses on controlling future risks for need for dialysis and symptom management, mainly pain and bleeding. Newly discovered molecules that may slow kidney cyst growth has recently switched attention from care and treatment toward preventing disease progression and symptom control.

In this review, we aimed to analyse the benefits and harms of interventions directed at preventing progression of ADPKD. The literature was searched to 6 June 2015. We found 30 studies (involving 2039 participants) that tested 11 different treatments.

Reported outcomes were mostly limited to kidney function and volume. In evidence largely limited to children, it was found that ACEi (angiotensin converting enzyme inhibitor) medicines significantly reduced diastolic blood pressure but had uncertain effects on kidney volumes and how well the kidneys work (tested by measuring the glomerular filtration rate (GFR) and serum creatinine level in patients' blood). In adults, ACEi did not show different effects on GFR and the amount of a protein called albumin in the urine (albuminuria) when compared with beta blockers, or serum creatinine when compared with drugs known as ARBs (angiotensin II receptor blockers). Evidence from a single study was inconclusive concerning the effects of vasopressin receptor 2 antagonists on kidney function and volumes; however, these drugs made patients thirsty and caused dry mouth. Compared with no treatment, the group of medicines known as mTOR inhibitors (mammalian target of rapamycin inhibitors) had uncertain effects on kidney function and volume but caused soft tissue swelling, mouth ulcers, infections and diarrhoea. Drugs known as somatostatin analogues slightly improved serum creatinine and total kidney volume but had no definite effects on GFR and caused diarrhoea. Data for other drugs were sparse and inconclusive.

There is currently insufficient evidence to show that drugs used for people with ADPKD can protect kidney function to delay needing dialysis or a kidney transplant. Further evidence from large, well-designed clinical studies is needed to inform healthcare decision making before these drugs can be chosen routinely to achieve better health outcomes for people with ADPKD.

Authors' conclusions: 

Although several interventions are available for patients with ADPKD, at present there is little or no evidence that treatment improves patient outcomes in this population and is associated with frequent adverse effects. Additional large randomised studies focused on patient-centred outcomes are needed.

Read the full abstract...

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited disorder causing kidney disease. Current clinical management of ADPKD focuses primarily on symptom control and reducing associated complications, particularly hypertension. In recent years, improved understanding of molecular and cellular mechanisms involved in kidney cyst growth and disease progression has resulted in new pharmaceutical agents to target disease pathogenesis to prevent progressive disease.


We aimed to evaluate the effects of interventions for preventing ADPKD progression on kidney function, kidney endpoints, kidney structure, patient-centred endpoints (such as cardiovascular events, sudden death, all-cause mortality, hospitalisations, BP control, quality of life, and kidney pain), as well as the general and specific adverse effects related to their use.

Search strategy: 

We searched the Cochrane Renal Group's Specialised Register to 6 June 2015 using relevant search terms.

Selection criteria: 

Randomised controlled trials (RCTs) comparing any interventions for preventing the progression of ADPKD with other interventions or placebo were considered for inclusion without language restriction.

Data collection and analysis: 

Two authors independently assessed study risks of bias and extracted data. We summarised treatment effects on clinical outcomes, kidney function and structure and adverse events using random effects meta-analysis. We assessed heterogeneity in estimated treatment effects using the Cochran Q test and I2 statistic. Summary treatment estimates were calculated as a mean difference (MD) or standardised mean difference (SMD) for continuous outcomes and a risk ratio (RR) for dichotomous outcomes together with their 95% confidence intervals.

Main results: 

We included 30 studies (2039 participants) that investigated 11 pharmacological interventions (angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARBs), calcium channel blockers, beta blockers, vasopressin receptor 2 (V2R) antagonists, mammalian target of rapamycin (mTOR) inhibitors, somatostatin analogues, antiplatelet agents, eicosapentaenoic acids, statins and vitamin D compounds) in this review.

ACEi significantly reduced diastolic blood pressure (9 studies, 278 participants: MD -4.96 mm Hg, 95% CI -8.88 to -1.04), but had uncertain effects on kidney volumes (MD -42.50 mL, 95% CI -115.68 to 30.67), GFR (MD -3.41 mL/min/1.73 m2, 95% CI -15.83 to 9.01), and SCr (MD -0.02 mg/dL, 95% CI -0.14 to 0.09), in data largely restricted to children. ACEi did not show different effects on GFR (MD -8.19 mL/min/1.73 m2, 95% CI -29.46 to 13.07) and albuminuria (SMD -0.19, 95% CI -1.77 to 1.39) when compared with beta-blockers, or SCr (MD 0.00 mg/dL, 95% CI -0.09 to 0.10) when compared with ARBs.

Data for effects of V2R antagonists on kidney function and volumes compared to placebo were limited to narrative information within a single study while these agents increased thirst (1444 participants: RR 2.70, 95% CI 2.24 to 3.24) and dry mouth (1455 participants: RR 1.33, 95% CI 1.01 to 1.76).

Compared with no treatment, mTOR inhibitors had uncertain effects on kidney function (2 studies, 115 participants: MD 4.45 mL/min/1.73 m2, 95% CI -3.20 to 12.11) and kidney volume (MD -0.08 L, 95% CI -0.75 to 0.59) but in three studies (560 participants) caused angioedema (RR 13.39, 95% CI 2.56 to 70.00), oral ulceration (RR 6.77, 95% CI 4.42 to 10.38), infections (RR 1.14, 95% CI 1.04 to 1.25) and diarrhoea (RR 1.70, 95% CI 1.26 to 2.29).

Somatostatin analogues (6 studies, 138 participants) slightly improved SCr (MD -0.43 mg/dL, 95% CI -0.86 to -0.01) and total kidney volume (MD -0.62 L, 95% CI -1.22 to -0.01) but had no definite effects on GFR (MD 9.50 mL/min, 95% CI -4.45 to 23.44) and caused diarrhoea (RR 3.72, 95% CI 1.43 to 9.68).

Data for calcium channel blockers, eicosapentaenoic acids, statins, vitamin D compounds and antiplatelet agents were sparse and inconclusive.

Random sequence generation was adequate in eight studies, and in almost half of the studies, blinding was not present or not specified. Most studies did not adequately report outcomes, which adversely affected our ability to assess this bias. The overall drop-out rate was over 10% in nine studies, and few were conducted using intention-to-treat analyses.