Autosomal dominant polycystic kidney disease (ADPKD), the leading monogenic cause of kidney failure, exhibits heterogeneous clinical progression. This systematic review and meta-analysis synthesize and evaluate current evidence on blood and urine prognostic biomarkers in ADPKD, addressing gaps in understanding their role in predicting progression and guiding clinical trial selection and management. We searched PubMed, Embase, and Cochrane up to April 2025 and screened articles in duplicate. We included longitudinal studies evaluating the blood and urine prognostic biomarkers in patients with ADPKD with at least 10 participants and 1 year of follow-up. We used the Quality in Prognosis Studies tool to assess risk of bias, random effects meta-analyses to pool effect estimates, and the GRADE approach to assess the certainty of evidence. We included 58 studies, with 33 urinary biomarkers and 29 serum/blood biomarkers identified. The most frequently studied biomarkers were urine osmolality, copeptin, proteinuria, Monocyte Chemoattractant Protein-1, and uric acid, whereas the most studied outcomes were estimated Glomerular Filtration Rate and Total Kidney Volume. The urinary biomarkers that showed the largest association with ADPKD were Monocyte Chemoattractant Protein-1, Kidney Injury Molecule-1, albumin, and Beta 2 microglobulin. Serum biomarkers associated with outcomes were primarily copeptin and Fibroblast Growth Factor-23, with β-Hydroxybutyrate and bicarbonate exhibiting lesser association. In conclusion, this systematic review highlights the potential prognostic value of blood and urine biomarkers in ADPKD. It also verified the need for further validation of biomarker use in ADPKD. Not applicable.

KEY POINTS:In an observational cohort of mostly non-Hispanic White women, pregnancy was not associated with later-life accelerated kidney function decline. Pregnancy occurring during the HALT Progression of Polycystic Kidney Disease (HALT-PKD) trial was not associated with kidney disease progression relative to women who did not become pregnant. Prior evidence indicates that adverse pregnancy outcomes may be involved in autosomal dominant polycystic kidney disease progression; pregnant women should be closely monitored. BACKGROUND:Data are conflicting regarding whether pregnancy influences disease progression in women with autosomal dominant polycystic kidney disease (ADPKD). This study examined whether pregnancy or number of pregnancies was associated with kidney disease progression in women with ADPKD. METHODS:Women with early- (study A) and late-stage (study B) ADPKD from the HALT Progression of Polycystic Kidney Disease (HALT-PKD) trial were included to examine the association between self-reported number of pregnancies (categorical predictor: no pregnancy versus 1-2 pregnancies and ≥3 pregnancies), annual slope of eGFR, annual percent change in total kidney volume (%ΔTKV), and a composite outcome (kidney failure, 50% decline in eGFR, or death) using multivariable linear regression and Cox proportional hazard models. In addition, women who became pregnant, had full-term pregnancies, and available data during study participation ( n =13) were propensity matched (1:4) to women who were not pregnant during study participation, and a mixed model was applied to determine the association of pregnancy with eGFR slope and %ΔTKV. RESULTS:Across all analyses, 455 women with a median age of 45 (interquartile range, 38-50) years and eGFR of 69±25 ml/min per 1.73 m 2 at baseline were included. One hundred ninety-nine women had 1-2 pregnancies, and 165 women had ≥3 pregnancies. There was no association of 1-2 pregnancies or ≥3 pregnancies (versus no pregnancies) with eGFR slope ( β -estimate [95% confidence interval (CI)]; 1-2 pregnancies: 0.22 [-0.44 to 0.89]; ≥3 pregnancies: -0.46 [-1.16 to 0.25]), %ΔTKV ( β -estimate [95% CI]; 1-2 pregnancies: 0.92 [-0.34 to 2.17]; ≥3 pregnancies: 0.69 [-0.67 to 2.04]), or time to composite outcome (hazard ratio [95% CI]; 1-2 pregnancies: 1.04 [0.56 to 1.93]; ≥3 pregnancies: 1.48 [0.78 to 2.77]) in adjusted models. Moreover, there was no difference in annual eGFR slope ( β -estimate: -0.14 [95% CI, -2.72 to 2.44]) and %ΔTKV ( β -estimate: 0.04 [95% CI, -3.74 to 3.82]) in women who became pregnant matched to women who did not became pregnant during their participation in the study. CONCLUSIONS:Pregnancy was not associated with ADPKD progression among women with early- and late-stage ADPKD enrolled in the HALT-PKD trial.

The Kelvin-Helmholtz instability (KHI) is a shear-driven phenomenon frequently observed at the Earth's low-latitude magnetopause when the velocity shear is super Alfvénic. KHI represents a way for plasmas to give rise to a turbulent scenario and to convert the energy due to the large-scale motion of the shear flow into heat. Indeed, the evolution of the KHI is characterized by the nonlinear coupling of different modes, which tends to generate smaller and smaller vortices along the shear layer. Both kinetic simulations and in situ measurements, focusing on the kinetic effects during the nonlinear phase of the instability, have shown the generation of strong current sheets between well-developed vortices, and temperature anisotropy and agyrotropy at both ion and electron scales, in accordance with the multi-scale nature of the phenomenon.Moreover, KHI is thought to play a crucial role in the transport of solar wind plasma into the magnetosphere and to efficiently contribute to the formation of the low latitude boundary layer. Although the instability threshold is equally satisfied during both northward and southward interplanetary magnetic field (IMF) conditions, in-situ measurements show that KHI privileges the northward orientation. We investigate this different behavior by analyzing the kinetic features at both boundaries and inside the KH structures. Thus, we statistically investigate several KHI crossings observed by the Magnetospheric Multiscale mission for different IMF orientations. Our statistical study can provide a better understanding about the global dynamics of the near Earth's environment and gives an important contribution to the solar wind-magnetosphere coupling mechanism.

Autosomal recessive polycystic kidney disease (ARPKD) is a rare, inherited condition associated with pathogenic variants in the PKHD1 gene, leading to fibrocystin dysfunction. ARPKD carries significant morbidity, involving progressive kidney dysfunction that often necessitates transplantation or dialysis. Liver complications commonly accompany renal manifestations and contribute to marked clinical heterogeneity and challenging disease management. Current therapies focus on alleviating complications rather than halting or reversing disease progression. Against this backdrop, patient-focused drug development (PFDD) has emerged to incorporate patients' perspectives and priorities into medical product development and care. On August 29, 2023, an externally led PFDD meeting brought together ARPKD patients, caregivers, clinicians, researchers, industry stakeholders, and regulators. These discussions highlighted the urgent need for treatments that address both renal and hepatic complications, improve quality of life, and mitigate disease burdens. This initiative also provided an opportunity to compare ARPKD patient-identified priorities with outcomes from previous Standard Outcome in Nephrology Group efforts. Commonalities included the emphasis on quality of life and functional measures. ARPKD- externally led PFDD-specific considerations were early-onset disease and combined kidney-liver pathology. Incorporating these insights into clinical trial designs and regulatory frameworks holds promise for more meaningful outcome measures and the advancement of ARPKD novel therapies.

Key PointsParticipants are less concerned about mortality than they are about kidney health.Psychological effect emerged as the most important theme regarding the effects of polycystic kidney disease on patients.BackgroundPatient involvement in research can help to ensure that the evidence generated aligns with their needs and priorities. In the Establishing Meaningful Patient-Centered Outcomes with Relevance for Patients with Polycystic Kidney Disease (PKD) project, we aimed to identify patient-important outcomes and discuss the effect of PKD on patients.MethodsNine focus groups were held with adult patients with PKD, caregivers, and clinical or research experts in PKD. We used a nominal, multivote technique to rank patient-important outcomes to be prioritized by future PKD research. We conducted a thematic analysis of verbatim transcriptions to identify themes regarding the effect of PKD on their daily lives. Other focus group topics included insurability and patient engagement.ResultsNinety patients and/or caregivers and eight clinicians and/or researchers participated in the focus groups. Nine focus groups yielded 35 outcomes important to patients that were grouped into six categories, ranked in order of importance: kidney health, comorbidities, lifestyle, psychological effect, family and awareness, and mortality. Regarding the effect of PKD on the patient's daily lives, we identified five themes, listed in order of importance: psychological effect, effect on daily living, issues affecting decision making, health care-related issues, and PKD-specific testing dilemmas.ConclusionsThis study of stakeholder engagement in patients with PKD revealed important priorities and values that should be considered for future research and when caring for patients with PKD. Future research should focus on kidney health and managing comorbidities in patients with PKD. This will help to bridge the knowledge gap and develop meaningful comparative effectiveness research in PKD.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic cause of kidney failure. Scientific advances have improved the approach to diagnosis, prognosis, and management of renal and extrarenal manifestations. The combination of total kidney volume, kidney function, and the genetic mutation (if known), predicts risk for progression to kidney failure, thereby identifying patients in whom disease modifying therapy is recommended. Currently there is one therapy approved by the US Food and Drug Administration (FDA) for slowing ADPKD progression, the V2 receptor antagonist, tolvaptan. Other therapies are under active investigation for ADPKD. This Core Curriculum discusses diagnosis and management of the renal and extrarenal manifestations seen in ADPKD including acute and chronic pain and cyst infection and polycystic liver disease and intracranial aneurysm. Management of hypertension and women's health and pregnancy management in ADPKD are covered. This review was aligned with the findings of the recently published Kidney Disease Improving Global Outcomes (KDIGO) clinical practice guideline for the Evaluation, Management, and Treatment of ADPKD.

Key PointsAcute effects impact the clinical endpoint independently of treatment effects on the chronic slope.Our findings support the 3-year total slope as the primary slope-based outcome in randomized trials.BackgroundSlope of the GFR is considered a validated surrogate endpoint for CKD trials. However, differing short-term and long-term treatment effects on GFR slope can create ambiguities concerning the appropriate period for evaluating slope, in part because current methods cannot separate the distinct contributions of the acute (before 3 months) and chronic (after 3 months) slopes for treatment effects on clinical endpoints (CEs).MethodsWe estimated treatment effects on the acute and chronic GFR slopes and on the established CE of kidney failure or serum creatinine doubling for 66 randomized treatment comparisons from previous CKD clinical trials. We used a novel Bayesian meta-regression framework to relate treatment effects on the established CE to both the acute and chronic slopes in a single multivariable model to determine the independent contributions of the acute and chronic slopes.ResultsTreatment effects on both the acute and chronic slopes independently predicted the treatment effect on the established CE with a high median R2 (95% credible interval) of 0.95 (0.79 to 1.00). For a fixed treatment effect on the chronic slope, each 1 ml/min per 1.73 m2 greater acute GFR decline for the treatment versus control increased the hazard ratio for the established CE by 11.4% (7.9%-15.0%), against the treatment. The optimal weights for the acute and chronic slopes were consistent with the 3-year total slope defined as the average slope extending from baseline to 3 years.ConclusionsTreatment effects on both the acute and chronic GFR slopes are independent determinants of the effects on the established CE, with variation in acute effects accounting for much of the observed variation in treatment effects on the CE across previous trials. Our results establish that acute effects affect the CE independently of treatment effects on the chronic slope and support the 3-year total slope as the primary slope-based outcome in randomized trials.

Rationale & Objective Data from clinical practice are needed to characterize the effectiveness of pharmacotherapy outside the controlled setting of clinical trials but lack an untreated placebo group for comparison. To assess the effectiveness of tolvaptan for autosomal dominant polycystic kidney disease (ADPKD) in nephrology practice, we performed a chart review of US patients and compared it with a historical matched control cohort. Study Design Patient data from charts were provided by US nephrologists who participated in an online survey. Historical control data for patients with ADPKD not treated with tolvaptan were extracted from a database of ADPKD clinical studies (Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease, HALT Progression of Polycystic Kidney Disease, and OVERTURE). Setting & Participants Nephrologist respondents (n=57) provided baseline data and up to 4 years of follow-up on estimated glomerular filtration rate (eGFR) for tolvaptan-treated adults (n=149). Historical ADPKD-affected controls were adults in Mayo imaging risk classes 1C-1E (ie, at increased risk of rapid progression, consistent with the tolvaptan indication). Exposure Cases had to receive tolvaptan continuously for >= 2 years. Historical controls received nontolvaptan standard of care, including various antihypertensive regimens. Outcome Annual rate of eGFR change. Analytical Approach Cases and controls were matched on baseline clinical characteristics (matched set A: age, sex, and chronic kidney disease stage [110 matched pairs]; matched set B: age, sex, and eGFR [98 matched pairs]) and compared using a mixed model. Results The annual rate of eGFR decline was slower in tolvaptan-treated patients versus historical controls, by 1.40mL/min/1.73m(2) (95% CI, 0.05-2.74; P=0.04) in set A. Set B demonstrated a similar trend: 1.18mL/min/1.73m(2) per year (95% CI, -0.22 to 2.58; P=0.10). Limitations Risk of bias from convenience sampling and potential residual confounding after case/historical control matching. Conclusions Tolvaptan was associated with slower eGFR decline in routine clinical practice, consistent with the results of controlled trials.

Background: Slope of the glomerular filtration rate (GFR) is considered a validated surrogate endpoint for chronic kidney disease (CKD) trials. However, differing short and long-term treatment effects on GFR slope can create ambiguities concerning the appropriate time period for evaluating slope, in part because current methods cannot separate the distinct contributions of the acute (before three months) and chronic (after three months) slopes for treatment effects on clinical endpoints. Methods: We estimated treatment effects on the acute and chronic GFR slopes and on the established clinical endpoint (CE) of kidney failure or serum creatinine doubling for 66 randomized treatment comparisons from previous CKD clinical trials. We used a novel Bayesian meta-regression framework to relate treatment effects on the established CE to both the acute and chronic slopes in a single multivariable model to determine the independent contributions of the acute and chronic slopes. Results: Treatment effects on both the acute and chronic slopes independently predicted the treatment effect on the established CE with a high median R 2 (95% credible interval) of 0.95 (0.79,1.00). For a fixed treatment effect on the chronic slope, each 1 mL/min/1.73m 2 greater acute GFR decline for the treatment vs. control increased the HR for the established CE by 11.4% (7.9%, 15.0%), against the treatment. The optimal weights for the acute and chronic slopes were consistent with the three-year total slope defined as the average slope extending from baseline to three years. Conclusion: Treatment effects on both the acute and chronic GFR slopes are independent determinants of the effects on the established CE, with variation in acute effects accounting for much of the observed variation in treatment effects on the CE across previous trials. Our results establish that acute effects impact the CE independently of treatment effects on the chronic slope, and support the three-year total slope as the primary slope-based outcome in randomized trials.

Ion velocity distribution functions in solar wind are often found to be non-Maxwellian. Streams of accelerated particles and temperature anisotropies are typical non-thermal features, whose origin is debated since the early years of in situ measurements. In order to disentangle the kinetic processes which may play a role in the generation of such distortions, particle double streams need to be identified and isolated. To this purpose, we have developed a numerical approach that leverages the clustering technique employed in machine learning. Here, we present the results obtained applying our technique to the ion distribution functions of a typical fast Alfvénic wind stream observed by Solar Orbiter-PAS in mid-September 2022, at a heliocentric distance of about 0.58 au. We could separate up to four ion families, namely proton core and beam and alpha core and beam. This allows us to characterize and compare their features, like the relative densities and temperatures. Differently from the better-known proton beam, alpha beam represents a relevant fraction of the alpha population, around 40%. Separating such a massive beam may shed new light on alpha kinetic features like the anomalous overheating mechanism. Moreover, the study of the velocity drift of the various ion populations indicates that both the alpha core and the alpha beam are sensitive to the Alfvénic fluctuations, and the surfing effect found in literature can be recovered only when considering the core and the beam as a single population.The similarities between proton and alpha beams would suggest a common generation mechanism, apparently due to local physical conditions in the plasma.

AbstractVelocity distribution functions (VDFs) measured by the Magnetospheric Multiscale (MMS) mission are complex 3D data sets that can be represented as a superposition of multiple beams. Recent work proposed the use of the Gaussian Mixture Model (GMM) to identify different populations. Here we investigate the approach by considering first synthetic distributions made by synthetically creating beams of either Maxwellian distributions or kappa distributions with varying power law index. By varying the inter‐beam average difference and the beam standard deviation we evaluate the ability of the GMM in recognizing correctly the beam. We then apply the method systematically to MMS data in the tail and in the dayside of the Earth's magnetosphere. The approach relies on a GMM algorithm to detect and characterize the number of distinct clusters within a VDF, and a model selection approach based on the Bayesian Information Criterion to determine the optimal number of clusters. The conclusion of the analysis is that the GMM can estimate the complexity of a VDF in terms of the number of optimal beams provided by information theory criteria. By evaluating the complexity of VDFs, we can identify regions of interest within the plasma where significant physical phenomena may be present.

Key PointsThe Autosomal Dominant Polycystic Kidney Disease Centers of Excellence Program aims to improve specialized care for autosomal dominant polycystic kidney disease patients. It introduces two designations to accommodate diverse care settings and enhance patient access to specialists: Center of Excellence and Partner Clinic.The program draws inspiration from successful models in other diseases, such as cystic fibrosis and muscular dystrophy, which have demonstrated the effectiveness of standardized care centers in improving patient outcomes.Key needs and programmatic goals identified through patient and clinician stakeholder interviews include establishing a core care team with defined referral processes, implementing mentorship and shared care models, providing patient navigation services, and offering education on expert consensus and care guidelines. The Autosomal Dominant Polycystic Kidney Disease (ADPKD) Centers of Excellence (COE) Program, launched by the Polycystic Kidney Disease Foundation in 2022, aims to bridge the gap in specialized care for individuals with ADPKD. This program seeks to enhance the availability of specialized clinicians and simplify the process for patients seeking expert care. It is founded on three pillars: improving care for all individuals with ADPKD, educating and empowering the community, and advancing polycystic kidney disease research. The program draws inspiration from successful models in other diseases, such as cystic fibrosis and muscular dystrophy, which have demonstrated the effectiveness of standardized care centers in improving patient outcomes. Patient and clinician stakeholder interviews have identified key areas where a national program could make a significant effect, including the need for a core care team with defined referral processes, mentorship and shared care models, patient navigation services, and education around expert consensus and care guidelines. The program introduces two designations to accommodate diverse care settings and enhance patient access to specialists: COE and Partner Clinic. The Partner Clinic designation ensures that patients in smaller community practices have access to specialized care through mentorship and guidance from experts at COE. The program also emphasizes the importance of specialized services, especially in underserved communities experiencing health disparities, to manage the complexities of ADPKD care. Patient focus groups have highlighted the need for care navigation services, centralized sources of knowledge, and access to local care. The program aims to address these needs by providing a structured framework for care coordination, enhancing patient self-advocacy, and improving overall outcomes for individuals with ADPKD.

Context. It has been recently accepted that the standard classification of the solar wind solely according to flow speed is outdated, and particular interest has been devoted to the study of the origin and evolution of so-called Alfvenic slow solar wind streams and to what extent such streams resemble or differ from fast wind. Aims. In March 2022, Solar Orbiter completed its first nominal phase perihelion passage. During this interval, it observed several Alfvenic streams, allowing for characterization of fluctuations in three slow wind intervals (AS1-AS3) and comparison with a fast wind stream (F) at almost the same heliocentric distance. Methods. This work makes use of Solar Orbiter plasma parameters from the Solar Wind Analyzer (SWA) and magnetic field measurements from the magnetometer (MAG). The magnetic connectivity to the solar sources of selected solar wind intervals was reconstructed using a ballistic extrapolation based on measured solar wind speed down to the (spherical) source surface at 2.5 Rs below which a potential field extrapolation was used to map back to the Sun. The source regions were identified using SDO/AIA observations. A spectral analysis of in situ measured magnetic field and velocity fluctuations was performed to characterize correlations, Alfvenicity, normalized cross-helicity, and residual energy in the frequency domain as well as intermittency of the fluctuations and spectral energy transfer rate estimated via mixed third-order moments. A machine learning technique was used to separate proton core, proton beam, and alpha particles and to study v-b correlations for the different ion populations in order to evaluate the role played by each population in determining the Alfvenic content of solar wind fluctuations. Results. The comparison between fast wind and Alfvenic slow wind intervals highlights the differences between the two solar wind regimes: The fast wind is characterized by larger amplitude fluctuations, and magnetic and velocity fluctuations are closer to equipartition of energy. In fact the Alfvenic slow wind streams appear to be on a spectrum of wind types, with AS1, originating from open field lines neighboring active regions and displaying similarities with the fast wind in terms of fluctuation amplitude and turbulence characteristics, but not with respect to the alpha particles and proton beams. The other two slow streams differed both in their sources as well as plasma characteristics, with AS2 coming from the expansion of a narrow coronal hole corridor and AS3 from a region straddling a pseudostreamer. The latter displayed the coldest and highest density but the slowest stream with the smallest fluctuation amplitude and greatest magnetic energy excess. It also showed the largest scatter in proton beam speeds and the greatest difference in speed between proton beam and alpha particles. Conclusions. This study shows how the old fast-slow solar wind dichotomy, already called into question by the observations of slower Alfvenic solar wind streams, should further be refined, as the Alfvenic slow wind, originating in different solar wind regions, show significant differences in density, temperature, and proton and alpha-particle properties in the inner heliosphere. The observations presented here provide the starting point for a better understanding of the origin and evolution of different solar wind streams as well as the evolving turbulence contained within.

The Kidney Disease: Improving Global Outcomes (KDIGO) 2025 Clinical Practice Guideline for the Evaluation, Management, and Treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD) represents the first KDIGO guideline on this subject. Its scope includes nomenclature, diagnosis, prognosis, and prevalence; kidney manifestations; chronic kidney disease (CKD) management and progression, kidney failure, and kidney replacement therapy; therapies to delay progression of kidney disease; polycystic liver disease; intracranial aneurysms and other extrarenal manifestations; lifestyle and psychosocial aspects; pregnancy and reproductive issues; pediatric issues; and approaches to the management of people with ADPKD. The guideline has been developed with patient partners, clinicians, and researchers around the world, with the goal to generate a useful resource for healthcare providers and patients by providing actionable recommendations. The development of this guideline followed an explicit process of evidence review and appraisal, based on a rigorous, formal systematic literature review. The strength of recommendations follows the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The guideline also provides practice points serving to direct clinical care or activities relating to areas for which a systematic review was not conducted. Limitations of the evidence are discussed. Research recommendations to address gaps in knowledge, and implications for policy and payment, are provided. The guideline targets a broad audience of healthcare providers, people living with ADPKD, and stakeholders involved in the various aspects of ADPKD care.

Albuminuria is a central biomarker in chronic kidney disease (CKD), used for the detection and prognosis of the disease. In clinical trials assessing CKD progression, change in the level of albuminuria is a candidate surrogate endpoint for kidney failure. Evaluation of the validity of this surrogate endpoint across a diverse range of interventions and populations is required to support its further acceptance. Here, in an individual participant data analysis of 48 randomized controlled trials (studies) involving 85,681 participants, we assessed the association between treatment effects on 6-month urinary albumin:creatinine ratio (UACR) change and the established clinical endpoint of kidney failure or doubling of serum creatinine concentrations. Across all trials, each 30% reduction in the geometric mean of the UACR in the treatment group relative to the control group was associated with an average of 19% lower hazard for the clinical endpoint (95% Bayesian credible interval (BCI): 5-30%); median coefficient of determination (R2) = 0.66 (95% BCI: 0.06-0.98). There was no clear evidence that this association varied by CKD etiology. These results provide further support for use of albuminuria change as a surrogate endpoint in CKD clinical trials.

Background: Autosomal dominant polycystic kidney disease (ADPKD) is a common, inherited nephropathy often resulting in kidney failure. It is genetically heterogeneous; along with the major genes, PKD1 and PKD2 , at least 8 others have been suggested. ALG8 pathogenic variants have been associated with autosomal dominant polycystic liver disease and implicated in ADPKD, while ALG9 has been suggested as an ADPKD gene, but details of the phenotypes and penetrance are unclear. Methods: We screened >3900 families with cystic kidneys and/or livers using global approaches to detect ALG8 or ALG9 pathogenic variants. In addition, population cohorts with sequence data (Genomics England 100kGP (100kGP), UK Biobank (UKBB), and Mayo Clinic Biobank (MCBB)), were screened for ALG8 / ALG9 pathogenic variants. Results: Multicenter screening of individuals with polycystic kidney and/or liver disease identified 51 (1.3%) ALG8 (7 multiplex) and 23 (0.6%) ALG9 (5 multiplex) families; frequencies that were ∼10x and ∼24x greater than non-polycystic kidney disease (PKD) controls. Analysis of individuals with PKD phenotypes in 100kGP, UKBB, and MCBB identified 9 ALG8 (0.39%) and 9 ALG9 (0.39%) families, an enriched frequency over controls. Two individuals had PKD1 and ALG8 pathogenic changes. Eighty-nine percent of individuals with ALG8 mutations with imaging in the entire MCBB had kidney cysts (56%, >10 cysts), with greater median kidney and liver cyst numbers than controls. For ALG9, 78% had kidney cysts (27%, >10 cysts). Individuals with ALG8 mutations typically had mild cystic kidneys with limited enlargement. Liver cysts were common (71%) with enlarged livers (>2L) found in 11/62 patients although surgical intervention was rare. The ALG9 kidney phenotype was also of mild cystic kidneys but enlarged livers were rare; for both genes chronic kidney disease or kidney failure were rare. Conclusions: ALG8 and ALG9 are defined as cystic kidney/liver genes but with limited penetrance for lower eGFR.

Electromagnetic Ion Cyclotron (EMIC) waves mediate energy transfer from the solar wind to the magnetosphere, relativistic electron precipitation, or thermalization of the ring current population, to name a few. How these processes take place depends on the wave properties, such as the wavevector and polarization. However, inferring the wavevector from in-situ measurements is problematic since one needs to disentangle spatial and time variations. Using 8 years of Magnetospheric Multiscale (MMS) mission observations in the dayside magnetosphere, we present an algorithm to detect proton-band EMIC waves in the Earth's dayside magnetosphere, and find that they are present roughly 15% of the time. Their normalized frequency presents a dawn-dusk asymmetry, with waves in the dawn flank magnetosphere having larger frequency than in the dusk, subsolar, and dawn near subsolar region. It is shown that the observations are unstable to the ion cyclotron instability. We obtain the wave polarization and wavevector by comparing Single Value Decomposition and Ampere methods. We observe that for most waves the perpendicular wavenumber (k(perpendicular to)) is larger than the inverse of the proton gyroradius (rho(i)), that is, k(perpendicular to)rho(i) > 1, while the parallel wavenumber is smaller than the inverse of the ion gyroradius, that is, k(& Vert;)rho(i) < 1. Left-hand polarized waves are associated with small wave normal angles (theta(Bk) < 30 degrees), while linearly polarized waves are associated with large wave normal angles (theta(Bk) > 30 degrees). This work constitutes, to our knowledge, the first attempt to statistically infer the full wavevector of proton-band EMIC waves observed in the outer magnetosphere.