Ferritin dysregulation is implicated in numerous pathological conditions; however, its role in autosomal dominant polycystic kidney disease (PKD) remains poorly understood. Ferritin expression is increased in cyst-lining epithelial cells and macrophages in both PKD mouse and human kidneys. To investigate the functional significance of ferritin/iron homeostasis in disease progression, we generated conditional knockout of ferritin heavy chain (FTH) in collecting duct or myeloid lineage cells of PKD mice. FTH deletion in either cell type did not impact renal cyst growth. Notably, loss of FTH expression was accompanied by compensatory upregulation of ferritin light chain (FTL) in both models. To assess the effects of systemic ferritin infusion, we administered ferritin (iron replete), apoferritin (iron deplete), or phosphate-buffered saline (PBS; vehicle control) to PKD mice. Ferritin but not apoferritin infusion led to splenomegaly in wild-type (WT) and PKD mice, with no obvious alterations in cyst progression. Notably, ferritin infusion led to focal accumulation of ferritin in macrophage-enriched regions within the kidneys of PKD, but not WT mice. Consistent with this, elevated iron was detected in the kidneys of ferritin-treated PKD mice but not in wild-type controls, suggesting dysfunctional ferritin trafficking. Mechanistically, we observed increased uptake of ferritin and dysregulation of ferritin receptors by renal cystic epithelial cells of PKD patients. Ferritin-enriched areas were positive for heme oxygenase 1 and represented high oxidative stress and fibrosis. Collectively, these findings demonstrate a disruption in ferritin handling and iron homeostasis in PKD. This altered iron trafficking promotes localized oxidative stress and fibrosis, contributing to disease progression.NEW & NOTEWORTHY Ferritin dysregulation in autosomal dominant polycystic kidney disease (ADPKD) reveals a novel disease mechanism. Although ferritin heavy chain deletion does not affect cyst growth, polycystic kidney disease (PKD) kidneys show compensatory ferritin light chain upregulation and abnormal ferritin trafficking. Iron-loaded ferritin accumulates in macrophage-rich regions, increasing oxidative stress and fibrosis. Enhanced ferritin uptake and receptor dysregulation in cystic epithelial cells highlight disrupted iron homeostasis as a previously unrecognized contributor to ADPKD progression.

Introduction: We have previously reported that overweight and obesity are independently associated with more rapid disease progression in adults with autosomal dominant polycystic kidney disease (ADPKD). In this study, we perform a cross-sectional analysis to evaluate whether overweight and obesity are also associated with renal blood flow (RBF) in this patient population. Methods: A total of 134 non-diabetic adults with ADPKD and estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 who participated in a randomized controlled trial of pravastatin therapy were categorized as normal weight, overweight, or obese, based on baseline adjusted body mass index (BMI), calculated after subtracting magnetic resonance imaging (MRI)-derived kidney and liver mass from body weight. RBF was measured by phase contrast MRI and adjusted for body surface area (BSA) prior to analysis. The association of baseline BMI with baseline RBF was assessed using multivariable linear regression models. Results: Participants were 40 ± 10 years (mean ± SD), 67% female, with a baseline RBF of 635 ± 214 mL/min/1.73 m2, and a baseline Chronic Kidney Disease Epidemiology (CKD-EPID) eGFR of 90 ± 21 mL/min/1.73 m2. BSA-adjusted RBF was lower in a stepwise manner with increasing BMI category. After adjustment for demographics, systolic blood pressure, blood glucose, high-density lipoprotein, blood pressure medication usage, eGFR, and height-adjusted total kidney volume, both overweight (β-estimate: −78.4; 95% CI: −155.3, −1.6) and obesity (β-estimate: −190.6; 95% CI: −307.4, −73.7) remained significantly associated with lower RBF as compared to normal weight participants. For every one unit increase in BMI, RBF was 10.4 mL/min/1.73 m2 lower (95% CI: −16.9, −3.9) in the fully adjusted model. Conclusion: Overweight and obesity are cross-sectionally associated with lower RBF in patients with early-stage ADPKD; however, these findings reflect associations only and do not provide insight into causality. Further research and longitudinal studies are needed to establish the temporal and causal nature of these relationships and to evaluate whether reduced RBF may be a mechanism by which obesity is associated with faster progression in patients with ADPKD.

Background Congenital fibrosis of the extraocular muscles type 1 (CFEOM1) is characterized by congenital, non-progressive ptosis and ophthalmoplegia and is most commonly caused by heterozygous pathogenic variants in KIF21A. The GJB2 c.223C>T (p.Arg75Trp) variant is associated with autosomal dominant hearing loss and may be accompanied by keratinizing skin manifestations. We report a family in which two pathogenic variants inherited from different parents coexisted in one proband. Case presentation An 8-year-old girl presented with bilateral ptosis, narrow palpebral fissures, and restricted eye movements since birth, without evident progression. She also had hearing impairment. Ophthalmic examination showed marked bilateral ptosis, compensatory chin elevation, and bilateral limitation of ocular movements in all directions, with more prominent vertical limitation. Bell’s phenomenon was absent bilaterally. Mild eyelid closure lag of approximately 2 mm was observed during gentle eye closure, whereas complete closure was achieved with forced closure. The patient had bilateral high hyperopia with astigmatism and subnormal best-corrected visual acuity for her age. Pure-tone audiometry indicated bilateral profound hearing loss. Type A tympanograms, absent acoustic reflexes, and absent distortion-product otoacoustic emissions supported cochlear dysfunction. Palmoplantar keratoderma-like changes were also observed. Trio whole-exome sequencing identified heterozygous KIF21A NM_001173464.2:c.2860C>T (p.Arg954Trp) and GJB2 NM_004004.6:c.223C>T (p.Arg75Trp) variants in the proband. The KIF21A variant was maternally inherited, whereas the GJB2 variant was paternally inherited. Candidate-site sequencing results provided in the laboratory report supported segregation of both variants within the family. Conclusions This patient had a dual molecular diagnosis caused by two independent autosomal dominant pathogenic variants. The KIF21A variant explained the CFEOM1 phenotype, whereas the GJB2 variant explained the hearing loss and might be associated with the palmoplantar keratoderma-like changes. Dual molecular diagnoses should be considered when a patient’s manifestations cannot be fully explained by a single disorder. In patients with CFEOM1, absent Bell’s phenomenon and incomplete eyelid closure should be considered when planning ptosis surgery because of the risk of postoperative exposure keratopathy.

INTRODUCTION:Sodium-glucose cotransporter 2 inhibitors (SGLT2is) have been shown to slow progressive loss of kidney function in both diabetic and nondiabetic proteinuric kidney diseases. Despite the benefits of SGLT2i in patients with chronic kidney disease, the potential benefits of SGLT2i in autosomal dominant polycystic kidney disease (ADPKD) have not been assessed. METHODS:This is a randomized, placebo-controlled trial with empagliflozin (Jardiance®) with a 1-year duration and 2 participating centers, including the University of Colorado Anschutz Medical Campus and the University of Maryland Medical Center. Fifty nondiabetic ADPKD patients aged 18-55 years and estimated glomerular filtration rate of 30-90 mL/min/1.73 m2 are randomized in 1:1 ratio to receive 10 mg/day empagliflozin or a matching placebo. After 1 month, the dose is increased to 25 mg/day empagliflozin/placebo in all patients tolerating the lower dose. Results (Outcomes): The primary outcomes are safety and tolerability of empagliflozin, the latter determined by the percentage of patients tolerating the 25 mg dose of study drug/placebo at the end of the 12-month period. Safety is assessed by the frequency of all adverse events (AEs) and of specific AEs, including acute kidney injury, compared to placebo. Secondary outcomes include changes in total kidney volume, kidney function, aortic stiffness, copeptin level, urinary kidney injury molecule-1, and PKD-specific Health-Related Quality of Life questionnaire. CONCLUSIONS:The outcomes of this pilot trial will provide important data regarding the safety and tolerability of empagliflozin in patients with ADPKD. Preliminary insight into the potential kidney and vascular benefits of SGLT2i will aid the design of future large-scale efficacy studies.

ADAMTS9 mutations cause the ciliopathies nephronophthisis and Joubert syndrome. Here we show that deletion of ADAMTS9 in the proximal nephron leads to polycystic kidney development in mice. In males, Adamts9 deletion cause kidneys to become highly cystic but remain small without undergoing enlargement, causing early postnatal lethality. Female mice on the other hand, develop cystic kidneys but progress slowly. ADAMTS9 deletion disrupted ciliogenesis by the loss of ciliary transition zone (TZ) protein TMEM67 cleavage, leading to loss of the MKS/B9 module - a key component of the ciliary gate. Functional analysis of all eight ciliopathy patient variants of ADAMTS9 identified to date, showed TMEM67 C-terminus failed to localize to the transition zone, thus disrupting a key regulatory mechanism in patient renal ciliogenesis. Modeling ADAMTS9-mediated TMEM67 cleavage utilizing our novel TMEM67-cleavage deficient mice revealed loss of TZ formation but not elevated canonical Wnt signaling as the underlying mechanism driving cystogenesis. We show that Adamts9 deletion leads to comparatively intense interstitial collagen deposition, which likely restricts kidney enlargement resulting in the characteristically small kidney phenotype in nephronophthisis and increased immune response. By comparative analysis of four interconnected polycystic kidney models in addition to Pkd1 and Pkd2 deleted kidneys, we identify differential collagen homeostasis is the principle determining factor deciphering cystic kidney size and type.

INTRODUCTION:Whether treatment with pravastatin mitigates kidney dysfunction in adult patients with early autosomal dominant polycystic kidney disease (ADPKD) is unknown. To answer this, we performed a prospective, randomized, controlled, double-blind clinical trial in 150 patients (52 males and 98 females; 25-60 years) with ADPKD, and an estimated glomerular filtration rate (eGFR) of 60 ml/min or more per 1.73 m2. METHODS:Patients were randomly assigned to receive 40 mg of pravastatin or a placebo for two years. The primary outcome was the annual change in height-adjusted total kidney volume (HtTKV). Secondary outcomes were the annual change in kidney blood flow by magnetic resonance angiography and the annual change in measured GFR (mGFR). RESULTS:Among the participants who underwent randomization, the annual rate of increase in HtTKV median (interquartile range) was 3.1% (1.4, 6.8) in the placebo and the pravastatin 4.3% (3.0, 6.6) group. The annual rate of decline in kidney blood flow (ml/min per 1.73 m2) was -32.7 (-62.1, -0.8) in placebo vs. -15.1 (-50.7, 14.4) in the pravastatin group. The median change in mGFR (ml/min per 1.73 m2) -2.3 (-5.1, 1.6) for placebo and -1.4 (-6.4, 2.0) for the pravastatin group. Overall, no parameter differed significantly between treatment groups. There was a similar trend in patients with faster disease progression (Mayo Imaging Class 1C, D, and E). CONCLUSIONS:Among adult patients with ADPKD and preserved kidney function, pravastatin did not slow the increase in HtTKV and had no effect on slowing the decline in kidney blood flow and kidney function compared to placebo. TRIAL REGISTRATION:Registered at ClinicalTrials.gov with study number NCT03273413.

Rationale & ObjectiveIn this pilot study, we hypothesized that autosomal dominant polycystic kidney disease (ADPKD) is characterized by impaired kidney oxidative metabolism that associates with kidney size and cyst burden.Study DesignCross-sectional study.Setting & ParticipantsTwenty adults with ADPKD (31±6 years of age, 65% women, BMI: 26.8 [22.7, 30.4] kg/m2, eGFR (2021 CKD-EPI Creatinine): 103±18 ml/min/1.73m2, height-adjusted total kidney volume [HtTKV]: 731±370 ml/m, Mayo Classifications: 1B [5%], 1C [42%], 1D [21%], 1E [32%]) and 11 controls in normal weight category (NWC; 25±3 years of age, 45% women, BMI: 22.5 [21.7, 24.2] kg/m2, eGFR: 113±15 ml/min/1.73m2, HtTKV: 159±31 ml/m) at the University of Colorado Anschutz Medical Campus.PredictorsADPKD status (yes/no) and severity (Mayo Classifications).OutcomesHtTKV and cyst burden by MRI, kidney oxidative metabolism and perfusion by 11C-acetate PET/CT, insulin sensitivity by hyperinsulinemic-euglycemic clamps (presented as ratio of M-value of steady state insulin concentration [M/I]).Analytical ApproachChi-square/Fisher’s exact tests used for categorical variables and t-tests/ Mann-Whitney U tests for continuous variables. Pearson correlation used to estimate the relationships between variables.ResultsCompared to NWC, participants with ADPKD exhibited lower mean±SD M/I ratio (0.586±0.205 vs. 0.424±0.171 (mg/kg lean/min) / (μIU/mL), p=0.04), lower median [p25, p75] cortical perfusion (1.93 [1.80, 2.09 vs. 0.68 [0.47, 1.04] mL/min/g, p<0.001) and lower median [p25, p75] total kidney oxidative metabolism (0.17 [0.16,0.19] vs. 0.14 [0.12, 0.15] min-1, p=0.001) in voxel-wise models excluding cysts. HtTKV correlated inversely with cortical perfusion (r:-0.83, p<0.001), total kidney oxidative metabolism (r:-0.61, p<0.001) and M/I (r:-0.41, p=0.03).LimitationsSmall sample size and cross-sectional design.ConclusionAdults with ADPKD and preserved kidney function exhibited impaired renal perfusion and kidney oxidative metabolism across a wide range of cysts and kidney enlargements.

Abstract Background Tubular biomarkers, which reflect tubular dysfunction or injury, are associated with incident chronic kidney disease and kidney function decline. Several tubular biomarkers have also been implicated in the progression of autosomal dominant polycystic kidney disease (ADPKD). We evaluated changes in multiple tubular biomarkers in four groups of patients with ADPKD who participated in one of two clinical trials (metformin therapy and diet-induced weight loss), based on evidence suggesting that such interventions could reduce tubule injury. Methods 66 participants (26 M/40 F) with ADPKD and an estimated glomerular filtration rate (eGFR) ≥ 30 ml/min/1.73m2 who participated in either a metformin clinical trial (n = 22 metformin; n = 23 placebo) or dietary weight loss study (n = 10 daily caloric restriction [DCR]; n = 11 intermittent fasting [IMF]) were included in assessments of urinary tubular biomarkers (kidney injury molecule-1 [KIM-1], fatty-acid binding protein [FABP], interleukin-18 [IL-18], monocyte chemoattractant protein-1 [MCP-1], neutrophil gelatinase-associated lipocalin [NGAL], clusterin, and human cartilage glycoprotein-40 [YKL-40]; normalized to urine creatinine), at baseline and 12 months. The association of baseline tubular biomarkers with both baseline and change in height-adjusted total kidney volume (HtTKV; percent change from baseline to 12 months) and estimated glomerular filtration rate (eGFR; absolute change at 12 months vs. baseline), with covariate adjustment, was also assessed using multiple linear regression. Results Mean ± s.d. age was 48 ± 8 years, eGFR was 71 ± 16 ml/min/1.73m2, and baseline BMI was 30.5 ± 5.9 kg/m2. None of the tubular biomarkers changed with any intervention as compared to placebo. Additionally, baseline tubular biomarkers were not associated with either baseline or change in eGFR or HtTKV over 12 months, after adjustments for demographics, group assignment, and clinical characteristics. Conclusions Tubular biomarkers did not change with dietary-induced weight loss or metformin, nor did they associate with kidney disease progression, in this cohort of patients with ADPKD.

Significance Statement Lower serum bicarbonate levels, even within the normal range, are strongly linked to risks of cardiovascular disease in CKD, possibly by modifying vascular function. In this randomized, controlled trial, treatment with sodium bicarbonate (NaHCO 3 ) did not improve vascular endothelial function or reduce arterial stiffness in participants with CKD stage 3b–4 with normal serum bicarbonate levels. In addition, NaHCO 3 treatment did not reduce left ventricular mass index. NaHCO 3 did increase plasma bicarbonate levels and urinary citrate excretion and reduce urinary ammonium excretion, indicating that the intervention was indeed effective. NaHCO 3 therapy was safe with no significant changes in BP, weight, or edema. These results do not support the use of NaHCO 3 for vascular dysfunction in participants with CKD. Background Lower serum bicarbonate levels, even within the normal range, are strongly linked to risks of cardiovascular disease in CKD, possibly by modifying vascular function. Prospective interventional trials with sodium bicarbonate (NaHCO 3 ) are lacking. Methods We conducted a randomized, double-blind, placebo-controlled trial examining the effect of NaHCO 3 on vascular function in 109 patients with CKD stage 3b–4 (eGFR 15–44 ml/min per 1.73 m 2 ) with normal serum bicarbonate levels (22–27 mEq/L). Participants were randomized 1:1 to NaHCO 3 or placebo at a dose of 0.5 mEq/lean body weight-kg per day for 12 months. The coprimary end points were change in brachial artery flow-mediated dilation (FMD) and change in aortic pulse wave velocity over 12 months. Results Ninety patients completed this study. After 12 months, plasma bicarbonate levels increased significantly in the NaHCO 3 group compared with placebo (mean [SD] difference between groups 1.35±2.1, P = 0.003). NaHCO 3 treatment did not result in a significant improvement in aortic pulse wave velocity from baseline. NaHCO 3 did result in a significant increase in flow-mediated dilation after 1 month; however, this effect disappeared at 6 and 12 months. NaHCO 3 resulted in a significant increase in 24-hour urine citrate and pH and a significant decrease in 24-hour urine ammonia. There was no significant change in left ventricular mass index, ejection fraction, or eGFR with NaHCO 3 . NaHCO 3 treatment was safe and well-tolerated with no significant changes in BP, antihypertensive medication, weight, plasma calcium, or potassium levels. Conclusion Our results do not support the use of NaHCO 3 for vascular dysfunction in participants with CKD and normal serum bicarbonate levels.

Introduction: Cerebrovascular dysfunction, characterized by increased brain pulsatile flow, reduced cerebrovascular reactivity, and cerebral hypoperfusion precedes the onset of dementia and is linked to cognitive dysfunction. Autosomal dominant polycystic kidney disease (ADPKD) may increase the risk of dementia, and intracranial aneurysms are more prevalent in ADPKD patients. However, cerebrovascular function has not been previously characterized in patients with ADPKD. Methods: Using transcranial Doppler, we compared middle cerebral artery (MCA) pulsatility index (PI, cerebrovascular stiffness) and MCA blood velocity response to hypercapnia (normalized for blood pressure and end-tidal CO2, cerebrovascular reactivity) in patients with early-stage ADPKD versus age-matched healthy controls. We also administered the NIH cognitive toolbox (cognitive function) and measured carotid-femoral pulse-wave velocity (PWV, aortic stiffness). Results: Fifteen participants with ADPKD (9F, 27 ± 4 yrs, eGFR: 106 ± 22 mL/min/1.73 m2) were compared to 15 healthy controls (8F, 29 ± 4 yrs, eGFR: 109 ± 14 mL/min/1.73 m2). MCA PI was unexpectedly lower in ADPKD (0.71 ± 0.07) versus controls (0.82 ± 0.09 AU; p < 0.001); however, normalized MCA blood velocity in response to hypercapnia did not differ between groups (2.0 ± 1.2 vs. 2.1 ± 0.8 %Δ/mm Hg; p = 0.85). Lower MCA PI was associated with a lower crystalized composite score (cognition), which persisted after adjustment for age, sex, eGFR, and education (β = 0.58, p = 0.007). There was no association of MCA PI with carotid-femoral PWV (r = 0.01, p = 0.96), despite greater carotid-femoral PWV in ADPKD, suggesting MCA PI reflects vascular properties other than arterial stiffness (such as low wall shear stress) in ADPKD. Discussion/Conclusion: MCA PI is lower in patients with ADPKD. Follow-up research on this observation is merited as low PI has been associated with intracranial aneurysm in other populations.

Freshly prepared spleen cells from concanavalin A stimulated mice incorporate [3H]thymidine into DNA which can be recovered in detergent-soluble (NP40) and detergent-insoluble forms. The presence of detergent-soluble forms occurs despite the fact that the cells are lysed at 4 degrees C in the presence or absence of 25 mM ethylenediaminetetraacetic acid. After a 2-h pulse with [3H]thymidine, the detergent-soluble fraction contains about 1-3% of the total cellular DNA but 25% of the total labeled high molecular weight material. Since the specific activity of the extensively purified DNA from the detergent-soluble fraction is considerably higher than that of chromosomal DNA, it meets the criteria for being metabolically active. We propose the name "MADS" DNA for metabolically active detergent-soluble DNA. MADS DNA has a density of 1.699 g/mL on cesium chloride gradients and a slightly higher G + C content than chromosomal DNA as determined by high-pressure liquid chromatography. Electrophoresis using native or denaturing agarose gels resolves MADS DNA into discreet sizes between 200 and 4500 base pairs. Nuclease S-1 treatment of native MADS DNA does not alter the size distribution as resolved by means of gel electrophoresis under denaturing conditions. Therefore, MADS DNA is not a collection of single-stranded Okazaki fragments. Southern blot analysis reveals that mitochondrial DNA is a minor component of higher molecular weights above the bulk of the DNA visualized either by staining with ethidium bromide or by incorporation of [3H]thymidine. Inhibitors of ribonucleotide reductase or DNA polymerase alpha inhibit incorporation of [3H]thymidine into MADS DNA, and hence chromosomal DNA synthesis is required for MADS DNA production. Since Southern blot analysis also reveals homology of larger fragments with the 32P-labeled 200 base pair fragment, the presence of repetitive sequences is suggested.

Patients with chronic kidney disease (CKD) are more likely to die of cardiovascular diseases, including cerebrovascular disease, than to progress to end-stage kidney disease. Cerebrovascular dysfunction, characterized by reduced cerebrovascular reactivity, cerebral hypoperfusion, and increased pulsatile flow within the brain, precedes the onset of dementia and is linked to cognitive dysfunction. However, whether impaired cerebrovascular function is present in non-dialysis dependent CKD is largely unknown. Using transcranial Doppler, we compared middle cerebral artery (MCA) blood velocity response to hypercapnia (normalized for blood pressure and end-tidal CO2; a measure of cerebrovascular reactivity) and MCA pulsatility index (PI; a measure of cerebrovascular stiffness) in patients with stage 3-4 CKD vs. age-matched healthy controls. We also administered the NIH cognitive toolbox (cognitive function), measured carotid-femoral pulse-wave velocity (PWV; aortic stiffness), and assessed ex vivo nitric oxide (NO) and reactive oxygen species (ROS) production from human brain endothelial cells incubated with serum obtained from study participants. MCA PI was higher in patients with CKD vs. controls; however, normalized MCA blood velocity response to hypercapnia did not differ between groups. Similar results were observed in a validation cohort of midlife and older adults divided by the median estimated glomerular filtration rate (eGFR). MCA PI was associated with greater large-elastic artery stiffness (carotid-femoral PWV), worse executive function (trails B time), lower eGFR, and higher ex vivo ROS production. These data suggest that impaired kidney function is associated with greater cerebrovascular stiffness, which may contribute to the known increased risk for cognitive impairment in patients with CKD.

Wang, Wei; You, Zhiying; Steele, Cortney; Gitomer, Berenice Y.; Chonchol, Michel; Nowak, Kristen L. Author Information

The development and continued expansion of numerous cysts in the kidneys is an invariant feature of autosomal dominant polycystic kidney disease (ADPKD). Baseline height corrected total kidney volume (HtTKV) assessed by magnetic resonance imaging (MRI) and age has emerged as an imaging biomarker for estimation of disease progression in adult patients and is the basis of the Mayo classification system.1 However, predicting prognosis in children is more complex. Despite the presence in cysts in the kidneys of young patients with ADPKD, kidney function may remain normal for many years.

Background: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the development and continued growth of multiple cysts in the kidneys leading to ultimate loss of kidney function in most patients. Currently, tolvaptan is the only agency approved therapy to slow kidney disease advancement in patients with faster progressing disease underscoring the need for additional ADPKD therapies suitable for all patients. We previously showed that pravastatin slowed kidney disease progression in children and young adults with ADPKD. However, the intervention has not been tested in an adult cohort. Aims: The aim of the study is to conduct a single center, randomized, placebo -controlled double -blinded clinical trial to determine the efficacy of pravastatin on slowing kidney disease progression in adult patients with early stage ADPKD. Methods: One hundred and fifty adult patients with ADPKD and eGFR >= 60 ml/min/1.73m2 will be enrolled in the study and randomized to receive 40 mg/day pravastatin or placebo for a period of 2 -years. Outcomes: The primary outcome of the trial is change in total kidney volume assessed by magnetic resonance imaging (MRI). Secondary outcomes include change in kidney function by iothalamate GFR and renal blood flow and markers of inflammation and oxidative stress. Conclusion: This study will assess the kidney therapeutic benefits of pravastatin in adult patients with ADPKD. The recruitment goal of 150 subjects was attained and the study is ongoing. Registration: This study is registered on Clinicaltrials.gov # NCT03273413