Urinary albumin excretion and cancer risk: the PREVEND cohort study.

BACKGROUND: Chronic kidney disease (CKD) is believed to be associated with an increased risk for cancer, especially urinary tract cancer. However, previous studies predominantly focused on the association of decreased estimated glomerular filtration rate (eGFR) with cancer. In this study, we investigated the association of albuminuria with cancer incidence, adjusted for eGFR. METHODS: We included 8490 subjects in the Prevention of Renal and Vascular End-stage Disease (PREVEND) observational study. Urinary albumin excretion (UAE) was measured in two 24-hour urine specimens at baseline. Primary outcomes were the incidence of overall and urinary tract cancer. Secondary outcomes were the incidence of other site-specific cancers, and mortality due to overall, urinary tract, and other site-specific cancers. RESULTS: Median baseline UAE was 9.4 (IQR, 6.3-17.8) mg/24 h. During a median follow-up of 17.7 years, 1341 subjects developed cancer (of which 177 were urinary tract cancers). After multivariable adjustment including eGFR, every doubling of UAE was associated with a 6% (hazard ratios (HR), 1.06, 95% confidence intervals (CI), 1.02-1.10), and 14% (HR, 1.14, 95% CI, 1.04-1.24) higher risk of overall and urinary tract cancer incidence, respectively. Except for lung and hematological cancer, no associations were found between UAE and the incidence of other site-specific cancer. Doubling of UAE was also associated with a higher risk of mortality due to overall and lung cancer. CONCLUSIONS: Higher albuminuria is associated with a higher incidence of overall, urinary tract, lung, and hematological cancer, and with a higher risk of mortality due to overall and lung cancers, independent of baseline eGFR.

Multidisciplinary management of chronic refractory pain in autosomal dominant polycystic kidney disease.

BACKGROUND: Chronic pain is often difficult to manage in autosomal dominant polycystic kidney disease (ADPKD) patients and sometimes even leads to nephrectomy. We analyzed the long-term efficacy of our innovative multidisciplinary protocol to treat chronic refractory pain that aims to preserve kidney function by applying among other sequential nerve blocks. METHODS: Patients were eligible if pain was present ≥3 months with a score of ≥50 on a visual analog scale (VAS) of 100, was negatively affecting quality of life and if there had been insufficient response to previous therapies, including opioid treatment. Treatment options were, in order, analgesics, cyst aspiration and fenestration, nerve blocks and nephrectomy. RESULTS: A total of 101 patients were assessed in our clinic (mean age 50 ± 11 years, 65.3% females). Eight patients were treated with medication, 6 by cyst aspiration or fenestration, 63 by nerve blocks and 6 received surgery as the first treatment option. Overall, 76.9% experienced a positive effect on pain complaints shortly after treatment. The VAS score was reduced from 60/100 to 20/100 (P < 0.001) and patients decreased their number of nonopioid and opioid analgesics significantly (P < 0.001, P = 0.01, respectively). A substantial number of the patients (n = 51) needed additional treatment. At the end of follow-up in only 13 patients (12.9%) was surgical intervention necessary: 11 nephrectomies (of which 10 were in patients already on kidney function replacement treatment), 1 liver transplantation and 1 partial hepatectomy. After a median follow-up of 4.5 years (interquartile range 2.5-5.3), 69.0% of the patients still had fewer pain complaints. CONCLUSIONS: These data indicate that our multidisciplinary treatment protocol appears effective in reducing pain in the majority of patients with chronic refractory pain, while postponing or even avoiding in most patients surgical interventions such as nephrectomy in most patients.

The Need for Routine Native Nephrectomy in the Workup for Kidney Transplantation in Autosomal Dominant Polycystic Kidney Disease Patients.

INTRODUCTION: There is no consensus if nor when a native nephrectomy should be performed in the workup for kidney transplantation in ADPKD patients. In our PKD Expertise Center, a restrictive approach is pursued in which nephrectomy is performed only in patients with severe complaints, i.e., in case of serious volume-related complaints, lack of space for the allograft, recurrent cyst infections, persistent cyst bleedings, or chronic refractory pain. We analyzed in a retrospective cohort study whether this approach is justified. METHODS: All ADPKD patients who received kidney transplantation between January 2000 and January 2019 were reviewed. Patients were subdivided into three groups: no nephrectomy (no-Nx), nephrectomy performed before (pre-Tx), or after kidney transplantation (post-Tx). Simultaneous nephrectomy together with transplantation were not performed in our center. RESULTS: 391 patients (54 ± 9 years, 55% male) were included. The majority of patients did not undergo a nephrectomy (n = 257, 65.7%). A nephrectomy was performed pre-Tx in 114 patients (29.2%). After Tx, nephrectomy was performed in only 30 patients (7.7%, median 4.4 years post-Tx). Surgery-related complication rates did not differ between both groups (38.3% pre-Tx vs. 27.0% post-Tx, p = 0.2), nor were there any differences in 10-year patient survival (74.4% pre-Tx vs. 80.7% post-Tx vs. 67.6% no-Nx, p = 0.4), as well as in 10-year death-censored graft survival (84.4% pre-Tx vs. 85.5% post-Tx vs. 90.0% no-Nx, p = 0.9). CONCLUSIONS: This study indicates that with a restrictive nephrectomy policy in the workup for kidney transplantation, only a part of ADPKD patients need a native nephrectomy.

Argus-T adjustable male sling: A follow-up study on urinary incontinence and patient's satisfaction.

AIMS: The use of Argus-T adjustable sling may be a promising alternative option for the treatment of urinary incontinence after radical prostatectomy, however long-term data is lacking. The aim of this study is to evaluate the long-term results of the Argus-T sling on incontinence rates, patient's quality of life and tape-related complications. METHODS: Patients were eligible if persistent stress incontinence was present ≥12 months after radical prostatectomy. Measurements included 24 h frequency volume micturition list, 24 h pad test, 24 h pad count and quality of life questionnaires. Argus-T adjustable sling was placed with a single perineal route incision approach. RESULTS: Seventy-eight patients were included, 69 ± 6 years, pre-intervention 24 h urinary loss 212 (75-385) g. Directly after surgery, 63.6% of the patients was completely dry, 79.2% of the patients reported greater than 90% improvement of their urinary loss and 92.2% > 50% improvement. Median follow-up time was 3.2 (2.5-6.1) years. After 5 years of follow-up, 53.3% of the patients were completely dry, 71.5% reported an improvement greater than 90% and 79.6% reported an improvement of greater than 50%. Patients with preoperative urinary loss less than 250 g reported significantly higher improvement of their urinary loss compared to patients with urinary loss ≥250 g (p = .02). Patients satisfaction was still increased after 5 years follow-up (70 ± 21 vs.16 ± 9, p < .001) and patients quality of life remained high (85 ± 20 vs. 88 ± 13, p = .1). Complications were mainly observed directly after surgery. Two patients (2.6%) needed reimplantation of the sling. CONCLUSION: These data indicate that Argus-T sling is an effective treatment option in obtaining substantial long-term incontinence relief in patients with invalidating moderate stress urinary incontinence after radical prostatectomy.

Use of the Urine-to-Plasma Urea Ratio to Predict ADPKD Progression.

BACKGROUND AND OBJECTIVES: Predicting disease progression in patients with autosomal dominant polycystic kidney disease (ADPKD) poses a challenge, especially in early-stage disease when kidney function is not yet affected. Ongoing growth of cysts causes maximal urine-concentrating capacity to decrease from early on. We therefore hypothesized that the urine-to-plasma urea ratio, as a reflection of the urine-concentrating capacity, can be used as a marker to predict ADPKD progression. DESIGN: The urine-to-plasma urea ratio was calculated by dividing concentrations of early morning fasting spot urine urea by plasma urea. First, this ratio was validated as surrogate marker in 30 patients with ADPKD who underwent a prolonged water deprivation test. Thereafter, association with kidney outcome was evaluated in 583 patients with ADPKD with a broad range of kidney function. Multivariable mixed-model regression was used to assess association with eGFR slope, and logarithmic regression to identify patients with rapidly progressive disease, using a cutoff of -3.0 ml/min per 1.73 m2 per year. The urine-to-plasma urea ratio was compared with established predictors, namely, sex, age, baseline eGFR, Mayo Clinic height-adjusted total kidney volume class, and PKD gene mutation. RESULTS: The maximal urine-concentrating capacity and urine-to-plasma urea ratio correlated strongly (R=0.90; P<0.001). Next, the urine-to-plasma urea ratio was significantly associated with rate of eGFR decline during a median follow-up of 4.0 (interquartile range, 2.6-5.0) years, both crude and after correction for established predictors (ß=0.58; P=0.02). The odds ratio of rapidly progressive disease was 1.35 (95% confidence interval, 1.19 to 1.52; P<0.001) for every 10 units decrease in urine-to-plasma urea ratio, with adjustment for predictors. A combined risk score of the urine-to-plasma urea ratio, Mayo Clinic height-adjusted total kidney volume class, and PKD mutation predicted rapidly progressive disease better than each of the predictors separately. CONCLUSIONS: The urine-to-plasma urea ratio, which is calculated from routine laboratory measurements, predicts disease progression in ADPKD in addition to other risk markers. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2021_01_27_CJN10470620_final.mp3.

Somatostatin in renal physiology and autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive cyst formation, leading to growth in kidney volume and renal function decline. Although therapies have emerged, there is still an important unmet need for slowing the rate of disease progression in ADPKD. High intracellular levels of adenosine 3',5'-cyclic monophosphate (cAMP) are involved in cell proliferation and fluid secretion, resulting in cyst formation. Somatostatin (SST), a hormone that is involved in many cell processes, has the ability to inhibit intracellular cAMP production. However, SST itself has limited therapeutic potential since it is rapidly eliminated in vivo. Therefore analogues have been synthesized, which have a longer half-life and may be promising agents in the treatment of ADPKD. This review provides an overview of the complex physiological effects of SST, in particular renal, and the potential therapeutic role of SST analogues in ADPKD.

Lanreotide Reduces Liver Growth In Patients With Autosomal Dominant Polycystic Liver and Kidney Disease.

BACKGROUND & AIMS: Polycystic liver disease is the most common extrarenal manifestation of autosomal dominant polycystic kidney disease (ADPKD). There is need for robust long-term evidence for the volume-reducing effect of somatostatin analogues. We made use of data from an open-label, randomized trial to determine the effects of lanreotide on height-adjusted liver volume (hTLV) and combined height-adjusted liver and kidney volume (hTLKV) in patients with ADPKD. METHODS: We performed a 120-week study comparing the reno-protective effects of lanreotide vs standard care in 305 patients with ADPKD (the DIPAK-1 study). For this analysis, we studied the 175 patients with polycystic liver disease with hepatic cysts identified by magnetic resonance imaging and liver volume ≥2000 mL. Of these, 93 patients were assigned to a group that received lanreotide (120 mg subcutaneously every 4 weeks) and 82 to a group that received standard care (blood pressure control, a sodium-restricted diet, and antihypertensive agents). The primary endpoint was percent change in hTLV between baseline and end of treatment (week 120). A secondary endpoint was change in hTLKV. RESULTS: At 120 weeks, hTLV decreased by 1.99% in the lanreotide group (95% confidence interval [CI], -4.21 to 0.24) and increased by 3.92% in the control group (95% CI, 1.56-6.28). Compared with the control group, lanreotide reduced the growth of hTLV by 5.91% (95% CI, -9.18 to -2.63; P < .001). Growth of hTLV was still reduced by 3.87% at 4 months after the last injection of lanreotide compared with baseline (95% CI, -7.55 to -0.18; P = .04). Lanreotide reduced growth of hTLKV by 7.18% compared with the control group (95% CI, -10.25 to -4.12; P < .001). CONCLUSIONS: In this subanalysis of a randomized trial of patients with polycystic liver disease due to ADPKD, lanreotide for 120 weeks reduced the growth of liver and combined liver and kidney volume. This effect was still present 4 months after the last injection of lanreotide. ClinicalTrials.gov, Number: NCT01616927.

Association of plasma somatostatin with disease severity and progression in patients with autosomal dominant polycystic kidney disease.

BACKGROUND: Somatostatin (SST) inhibits intracellular cyclic adenosine monophosphate (cAMP) production and thus may modify cyst formation in autosomal dominant polycystic kidney disease (ADPKD). We investigated whether endogenous plasma SST concentration is associated with disease severity and progression in patients with ADPKD, and whether plasma SST concentrations change during treatment with a vasopressin V2 receptor antagonist or SST analogue. METHODS: In this observational study, fasting concentrations of SST were measured in 127 ADPKD patients (diagnosed upon the revised Ravine criteria) by ELISA. cAMP was measured in 24 h urine by Radio Immuno Assay. Kidney function was measured (mGFR) as 125I-iothalamate clearance, and total kidney volume was measured by MRI volumetry and adjusted for height (htTKV). Disease progression was expressed as annual change in mGFR and htTKV. Additionally, baseline versus follow-up SST concentrations were compared in ADPKD patients during vasopressin V2 receptor antagonist (tolvaptan) (n = 27) or SST analogue (lanreotide) treatment (n = 25). RESULTS: In 127 ADPKD patients, 41 ± 11 years, 44% female, eGFR 73 ± 32 ml/min/1.73m2, mGFR 75 ± 32 ml/min/1.73m2 and htTKV 826 (521-1297) ml/m, SST concentration was 48.5 (34.3-77.8) pg/ml. At baseline, SST was associated with urinary cAMP, mGFR and htTKV (p = 0.02, p = 0.004 and p = 0.02, respectively), but these associations lost significance after adjustment for age and sex or protein intake (p = 0.09, p = 0.06 and p = 0.15 respectively). Baseline SST was not associated with annual change in mGFR, or htTKV during follow-up (st. ß = - 0.02, p = 0.87 and st. ß = - 0.07, p = 0.54 respectively). During treatment with tolvaptan SST levels remained stable 38.2 (23.8-70.7) pg/mL vs. 39.8 (31.2-58.5) pg/mL, p = 0.85), whereas SST levels decreased significantly during treatment with lanreotide (42.5 (33.2-55.0) pg/ml vs. 29.3 (24.8-37.6), p = 0.008). CONCLUSIONS: Fasting plasma SST concentration is not associated with disease severity or progression in patients with ADPKD. Treatment with lanreotide caused a decrease in SST concentration. These data suggest that plasma SST cannot be used as a biomarker to assess prognosis in ADPKD, but leave the possibility open that change in SST concentration during lanreotide treatment may reflect therapy efficacy.

Effect of Lanreotide on Kidney Function in Patients With Autosomal Dominant Polycystic Kidney Disease: The DIPAK 1 Randomized Clinical Trial.

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 m2. 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 m2 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 m2 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. Trial Registration: ClinicalTrials.gov Identifier: NCT01616927.

Urinary renin-angiotensin markers in polycystic kidney disease.

In autosomal dominant polycystic kidney disease (ADPKD), activation of the renin-angiotensin aldosterone system (RAAS) may contribute to hypertension and disease progression. Although previous studies have focused on circulating RAAS components, preliminary evidence suggests that APDKD may increase urinary RAAS components. Therefore, our aim was to analyze circulating and urinary RAAS components in ADPKD. We cross-sectionally compared 60 patients with ADPKD with 57 patients with non-ADPKD chronic kidney disease (CKD). The two groups were matched by sex, estimated glomerular filtration rate (eGFR), blood pressure, and RAAS inhibitor use. Despite similar plasma levels of angiotensinogen and renin, urinary angiotensinogen and renin excretion were five- to sixfold higher in ADPKD (P < 0.001). These differences persisted when adjusting for group differences and were present regardless of RAAS inhibitor use. In multivariable analyses, ADPKD, albuminuria, and the respective plasma concentrations were independent predictors for urinary angiotensinogen and renin excretion. In ADPKD, both plasma and urinary renin correlated negatively with eGFR. Total kidney volume correlated with plasma renin and albuminuria but not with urinary renin or angiotensinogen excretions. Albuminuria correlated positively with urinary angiotensinogen and renin excretions in ADPKD and CKD. In three ADPKD patients who underwent nephrectomy, the concentrations of albumin and angiotensinogen were highest in plasma, followed by cyst fluid and urine; urinary renin concentrations were higher than cyst fluid. In conclusion, this study shows that, despite similar circulating RAAS component levels, higher urinary excretions of angiotensinogen and renin are a unique feature of ADPKD. Future studies should address the underlying mechanism and whether this may contribute to hypertension or disease progression in ADPKD.

The effect of office based flexible and rigid cystoscopy on pain experience in female patients.

PURPOSE: Rigid and flexible cystoscopies are both routinely used in female patients. Literature is conflicting whether flexible cystoscopy is less painful compared to rigid cystoscopy. The aim of this study was therefore to investigate whether using flexible cystoscopy leads to less discomfort and pain compared to rigid cystoscopy in female patients who underwent first time cystoscopy. MATERIALS AND METHODS: One hundred eighty-nine female patients, who never had undergone cystoscopy, were randomized into 2 groups: 92 patients underwent rigid cystoscopy and 97 patients flexible cystoscopy. Directly after the cystoscopy procedure all patients were asked to fill out their pain experience on a 100-mm visual analogue pain scale (VAS). RESULTS: Median VAS score was significantly lower for women undergoing flexible cystoscopy (0 [0-20]) compared to rigid cystoscopy (15 [0-38], p<0.001). In addition, age was inversely associated with VAS score, indicating that younger females experienced more pain (R=-0.30, p=0.001). The use of flexible cystoscopy was associated with a decrease in VAS score and remained significant after adjustment for age, sex of urologist, performing urologist and indication (standardized ß=-0.17, p=0.048). CONCLUSIONS: The use of flexible cystoscopy resulted in a significantly lower pain experience compared to rigid cystoscopy. Based on patient's pain experience during cystoscopy, this study implicates to use flexible cystoscopy in female patients who undergo first time cystoscopy.

Polyuria due to vasopressin V2 receptor antagonism is not associated with increased ureter diameter in ADPKD patients.

BACKGROUND: Tolvaptan, a vasopressin V2 receptor antagonist, has been shown to reduce the rates of growth in total kidney volume (TKV) and renal function loss in ADPKD patients, but also leads to polyuria because of its aquaretic effect. Prolonged polyuria can result in ureter dilatation with consequently renal function loss. Therefore, we aimed to investigate the effect of tolvaptan-induced polyuria on ureter diameter in ADPKD patients. METHODS: 70 ADPKD patients were included (51 were randomized to tolvaptan and 19 to placebo). At baseline and after 3 years of treatment renal function was measured (mGFR) and MRI was performed to measure TKV and ureter diameter at the levels of renal pelvis and fifth lumbar vertebral body (L5). RESULTS: In these patients [65.7 % male, age 41 ± 9 years, mGFR 74 ± 27 mL/min/1.73 m2 and TKV 1.92 (1.27-2.67) L], no differences were found between tolvaptan and placebo-treated patients in 24-h urine volume at baseline (2.5 vs. 2.5 L, p = 0.8), nor in ureter diameter at renal pelvis and L5 (4.0 vs. 4.2 mm, p = 0.4 and 3.0 vs. 3.1 mm, p = 0.3). After 3 years of treatment 24-h urine volume was higher in tolvaptan-treated patients when compared to placebo (4.7 vs. 2.3 L, p < 0.001), but no differences were found in ureter diameter between both groups (renal pelvis: 4.2 vs. 4.4 mm, p = 0.4 and L5: 3.1 vs. 3.3 mm, p = 0.4). CONCLUSIONS: Tolvaptan-induced polyuria did not lead to an increase in ureter diameter, suggesting that tolvaptan is a safe therapy from a urological point of view.

Management of renal cyst infection in patients with autosomal dominant polycystic kidney disease: a systematic review.

Background: Renal cyst infection is one of the complications faced by patients with autosomal dominant polycystic kidney disease (ADPKD). Cyst infection is often difficult to treat and potentially leads to sepsis and death. No evidence-based treatment strategy exists. We therefore performed a systematic review to develop an effective approach for the management of renal cyst infection in ADPKD patients based on the literature. Methods: A systematic search was performed in PubMed (January 1948-February 2014), EMBASE (January 1974-February 2014) and the Cochrane Library (until February 2014) according to the PRISMA guidelines. Results: We identified 60 manuscripts that included 85 ADPKD patients with renal cyst infection (aged 52 ± 12 years, 45% male, 27% on dialysis, 13% history of renal transplantation and 6% diabetes mellitus). Included patients received a total of 160 treatments of which 92 were antimicrobial, 29 percutaneous and 39 surgical. Initial management often consisted of antimicrobials (79%), and quinolone-based regimens were favoured (34%). Overall, 61% of patients failed initial treatment, but treatment failure has decreased over time (before the year 2000: 75%; during and after the year 2000: 51%, P = 0.03). Post-renal obstruction, urolithiasis, atypical or resistant pathogens, short duration of antimicrobial treatment and renal function impairment were documented in patients failing treatment. Conclusions: First-line treatment of renal cyst infection in ADPKD consists of antimicrobials and is associated with a high rate of failure, but treatment success has increased over recent years. A large-scale unbiased registry is needed to define the optimal strategy for renal cyst infection management in ADPKD.

Hepatic Cyst Infection During Use of the Somatostatin Analog Lanreotide in Autosomal Dominant Polycystic Kidney Disease: An Interim Analysis of the Randomized Open-Label Multicenter DIPAK-1 Study.

INTRODUCTION AND AIMS: The DIPAK-1 Study investigates the reno- and hepatoprotective efficacy of the somatostatin analog lanreotide compared with standard care in patients with later stage autosomal dominant polycystic kidney disease (ADPKD). During this trial, we witnessed several episodes of hepatic cyst infection, all during lanreotide treatment. We describe these events and provide a review of the literature. METHODS: The DIPAK-1 Study is an ongoing investigator-driven, randomized, controlled, open-label multicenter trial. Patients (ADPKD, ages 18-60 years, estimated glomerular filtration rate 30-60 mL/min/1.73 m2) were randomized 1:1 to receive lanreotide 120 mg subcutaneously every 28 days or standard care during 120 weeks. Hepatic cyst infection was diagnosed by local physicians. RESULTS: We included 309 ADPKD patients of which seven (median age 53 years [interquartile range: 48-55], 71% female, median estimated glomerular filtration rate 42 mL/min/1.73 m2 [interquartile range: 41-58]) developed eight episodes of hepatic cyst infection during 342 patient-years of lanreotide use (0.23 cases per 10 patient-years). These events were limited to patients receiving lanreotide (p < 0.001 vs. standard care). Baseline characteristics were similar between subjects who did or did not develop a hepatic cyst infection during lanreotide use, except for a history of hepatic cyst infection (29 vs. 0.7%, p < 0.001). Previous studies with somatostatin analogs reported cyst infections, but did not identify a causal relationship. CONCLUSIONS: These data suggest an increased risk for hepatic cyst infection during use of somatostatin analogs, especially in ADPKD patients with a history of hepatic cyst infection. The main results are still awaited to fully appreciate the risk-benefit ratio. CLINICALTRIALS. GOV IDENTIFIER: NCT 01616927.

Bilateral cysts in the choroid plexus in a patient with autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) is a genetic systemic disorder, which is associated with cyst formation in several organs, renal function decline and a higher prevalence of intracranial aneurysms. We report a 52-year-old, otherwise healthy, man with ADPKD who had asymptomatic, bilateral, multiple cysts in the choroid plexus, which is an extremely rare abnormality. Recent evidence suggests that the polycystin proteins, which are dysfunctional in ADPKD, are found in ciliated choroid plexus cells that are involved with regulation of cerebrospinal fluid homeostasis. We hypothesize therefore that choroid plexus cysts may be part of the ADPKD phenotype, which has not been described before.