Mother-child correlation of kidney function: data from the Yamanashi Adjunct Study of Japan Environment and Children's Study (JECS).

BACKGROUND: Individual variation in kidney function can be affected by both congenital and acquired factors, and kidney function in children is possibly correlated with that in their mothers. However, the mother-child correlation in kidney function remains directly unconfirmed. METHODS: We conducted a cross-sectional study of 655 healthy pairs of 7- or 8-year-old children and their mothers as an adjunct study of a nationwide epidemiological study (Japan Environment and Children's Study). RESULTS: Both serum creatinine level (all children, r = 0.324, p < 0.001; girls, r = 0.365, p < 0.001; boys, r = 0.278, p < 0.001) and estimated glomerular filtration rate (eGFR) (r = 0.274, p < 0.001; r = 0.352, p < 0.001; r = 0.195, p < 0.001, respectively) in children were weakly associated with their maternal values. In the single linear regression analyses, maternal values of serum creatinine and eGFR were significantly associated with the children's values. Moreover, several body composition values in children, such as weight-SDS, fat (%), and predicted muscle weight, were also significantly associated with kidney function values in children. In the multiple linear regression analysis for serum creatinine levels in children, in which weight-SDS and predicted muscle weight in children were selected as adjustment factors, maternal serum creatinine level showed a significant positive association (B = 0.214, p < 0.001 in the adjusted model). Moreover, in the multiple linear regression analysis for eGFR value in children, in which fat (%) and predicted muscle weight in children were selected as adjustment factors, maternal eGFR values showed a significant positive association (B = 0.319, p < 0.001). CONCLUSIONS: We directly confirmed mother-child correlations in both serum creatinine levels and eGFR values, particularly in girls. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information.

The Effects of Sacran, a Sulfated Polysaccharide, on Gut Microbiota Using Chronic Kidney Disease Model Rats.

The aim of this study was to investigate the beneficial effects of sacran, a sulfated polysaccharide, on renal damage and intestinal microflora, in 5/6 nephrectomy rats as a model for chronic kidney disease (CKD). 5/6 Nephrectomy rats were divided into sacran treated and non-treated groups and examined for lethality after 4 weeks. The 5/6 nephrectomy rats were also divided into three groups: sacran treated, non-treated and AST-120 treated groups, and treated orally in a concentration-dependent manner for 4 weeks. Renal function was estimated by biochemical and histopathological analyses. Metagenomic analysis of feces from each group after 4 weeks was also performed and changes in intestinal microflora were compared. The administration of sacran to CKD rats at ≥19 mg/d increased their survival. In addition, the sacran-treated group improved CKD-related parameters in a concentration-dependent manner, and the inhibitory effect of 40 mg/d of sacran was comparable to that of AST-120. The changes in the intestinal microflora of the sacran treated group were positively correlated with an increase in the number of Lactobacillus species, which are known to be rich in beneficial bacteria, and the increment of this beneficial bacteria was negatively correlated with the concentration of indoxyl sulfate, a uremic toxin, in plasma. These results strongly suggest that the oral administration of sacran could contribute to the stabilization of intestinal microflora in CKD rats and to the reduction of oxidative stress as well as the inhibition of progression of CKD.

Prevention Measures for COVID-19 and Changes in Kawasaki Disease Incidence.

BACKGROUND: Kawasaki disease is suspected to be triggered by previous infection. The prevention measures for coronavirus disease 2019 (COVID-19) have reportedly reduced transmission of certain infectious diseases. Under these circumstances, the prevention measures for COVID-19 may reduce the incidence of Kawasaki disease. METHODS: We conducted a retrospective study using registration datasets of patients with Kawasaki disease who were diagnosed in all 11 inpatient pediatric facilities in Yamanashi Prefecture. The eligible cases were 595 cases that were diagnosed before the COVID-19 pandemic (from January 2015 through February 2020) and 38 cases that were diagnosed during the COVID-19 pandemic (from March through November 2020). Incidence of several infectious disease were evaluated using data from the Infectious Disease Weekly Report conducted by the National Institute of Infectious Diseases. RESULTS: Epidemics of various infectious diseases generally remained at low levels during the first 9 months (March through November 2020) of the COVID-19 pandemic. Moreover, the incidence of COVID-19 was 50-80 times lower than the incidence in European countries and the United States. The total number of 38 cases with Kawasaki disease for the 9 months during the COVID-19 pandemic was 46.3% (-3.5 standard deviations [SDs] of the average [82.0; SD, 12.7 cases] for the corresponding 9 months of the previous 5 years. None of the 38 cases was determined to be triggered by COVID-19 based on their medical histories and negative results of severe acute respiratory syndrome coronavirus 2 testing at admission. CONCLUSION: These observations provide a new epidemiological evidence for the notion that Kawasaki disease is triggered by major infectious diseases in children.

Sacran, a sulfated polysaccharide, suppresses the absorption of lipids and modulates the intestinal flora in non-alcoholic steatohepatitis model rats.

AIMS: The objective of this study was to investigate the effects of administering sacran, a sulfated polysaccharide, on liver biology, gut microbiota, oxidative stress, and inflammation on stroke-prone spontaneously hypertensive (SHRSP5/Dmcr) rats that develop fibrotic steatohepatitis with histological similarities to that of non-alcoholic steatohepatitis (NASH). MAIN METHODS: Four groups of 8-week-old SHRSP5/Dmcr rats were fed a high fat-cholesterol (HFC) diet for 4 and 8 weeks and administered either sacran (80 mg/kg/day) or a non-treatment, respectively. Liver function was evaluated by biochemical and histopathological analyses. Hepatic inflammatory markers were measured using mRNA expression. Fecal microbial profiles were determined via 16S rRNA sequencing. A triglyceride (TG) absorption test was administered to the 8-week-old Sprague-Dawley (SD) rats. KEY FINDING: Sacran administration was observed to decrease the extent of oxidative stress and hepatic biochemical parameters in serum and hepatic injury with the levels of transforming growth factor-beta (TGF-ß1) and tumor necrosis factor-alpha (TNF-α), being increased compared to those of the non-treatment group. At the genus level, sacran administration caused a significant decrease in the harmful Prevotella genus, and a significant increase in the useful Blautia genus was observed. Sacran administration also decreased the serum TG increase that was induced by administering corn oil to the SD rats. SIGNIFICANCE: We conclude that sacran administration has the potential to reduce the absorption of lipids into blood and to improve several gut microbiotas, in the gastrointestinal tract, thereby inhibiting the subsequent development of oxidative stress and hepatic markers in the systematic circulation on NASH.

Association of Self-Reported Medication Adherence with Potentially Inappropriate Medications in Elderly Patients: A Cross-Sectional Pilot Study.

BACKGROUND: Polypharmacy (PP) and potentially inappropriate medications (PIMs) cause problematic drug-related issues in elderly patients; however, little is known about the association between medication adherence and PP and PIMs. This study evaluated the association of self-reported medication adherence with PP and PIMs in elderly patients. METHODS: A cross-sectional pilot study was conducted using data collected from electronic medical records of 142 self-administering patients aged ≥65 years, excluding emergency hospitalization cases. Self-reported medication adherence was assessed using the visual analogue scale (VAS). RESULTS: Of the 142 patients, 91 (64.1%) had PP and 80 (56.3%) used at least one PIM. In univariate analysis, patients with a VAS score of 100% had a significantly higher number of female patients and ≥1 PIM use compared to other patients. We found no association between the VAS score and PP. In multivariable analysis, the use of PIMs was significantly associated with a VAS score of 100% (odds ratio = 2.32; 95% confidence interval = 1.16-4.72; p = 0.017). CONCLUSIONS: Use of PIMs by elderly patients is significantly associated with self-reported medication adherence. Pharmacists should pay more attention to prescribed medications of self-administering elderly patients in order to improve their prescribing quality.

Effects of surface-deacetylated chitin nanofibers on non-alcoholic steatohepatitis model rats and their gut microbiota.

Nonalcoholic steatohepatitis (NASH), a more advanced form of nonalcoholic fatty liver disease (NAFLD), is associated with increased cardiovascular and liver-related mortality. Stroke-prone spontaneously hypertensive rats (SHRSP5/Dmcr) that are fed a high-fat and high-cholesterol diet develop hepatic lesions that are similar to those observed in human NASH pathology. We investigated the hepatic protective and antioxidant effects of surface-deacetylated chitin nanofibers (SDACNFs) that were administered to SHRSP5/Dmcr rats for 8 weeks. The administration of SDACNFs (80 mg/kg/day) resulted in a significant decrease in hepatic injury, oxidative stress, compared with the non-treatment. The SDACNFs also caused a reduction in the population of harmful members of the Morganella and Prevotella genus, and increased the abundance of the Blautia genus, a useful bacterium in gut microbiota. We therefore conclude that SDACNF exerts anti-hepatic and antioxidative effects not only by adsorbing lipid substances but also by reforming the community of intestinal microflora in the intestinal tract.

Physical activity and its related factors in Japanese people with haemophilia.

INTRODUCTION: In the general population, benefits of physical activity (PA) include improvement of physical function, prevention of lifestyle diseases and improvement of bone mineral content and quality of life. PA is recommended for patients with haemophilia (PwH), especially for those receiving advanced haemostatic treatment. We hypothesised many PwH engage in insufficient PA. AIM: This study aimed to clarify PA levels and the associated factors in Japanese PwH. METHODS: Physical activity was assessed using the International Physical Activity Questionnaire short version, and basic data, activities of daily living (ADLs) and self-efficacy were also collected. RESULTS: A total of 106 questionnaires were completed. The average age of participant was 40.8 years. The median PA was 693.0 metabolic equivalent-min/wk. More than half of the participants (59.4%) were classified into the low activity group. PA showed a significant inverse correlation with age (P = 0.022) and a positive correlation with self-efficacy (P = 0.018). However, PA did not show a significant relationship with haemophilic severity, prophylactic treatment, annual intra-articular bleeding frequency, body mass index and ADL. In PwH receiving guidance in sports, such as activities that are safe to participate in or performing prophylaxis prior to a physical activity, self-efficacy was significantly higher (P = 0.033), ADL was better (P < 0.001), and mean age was younger (P = 0.01) than in those not receiving guidance in sports. CONCLUSION: As for PA level, 60% of the subjects showed low activity. To promote PA in PwH, improvement of self-efficacy and appropriate guidance may be necessary.

Investigation of a Dipeptidyl Peptidase-4 Inhibitor/Thiazolidinedione Combination Drug for Patients With Type 2 Diabetes and Poor Glycemic Control: Difficulty With Patient Enrollment.

BACKGROUND: One of the treatment options for type 2 diabetes mellitus (DM) is a combination drug (CD) that contains the dipeptidyl peptidase-4 inhibitor (DPP4I) alogliptin (AG) together with pioglitazone (PG). This CD can improve impaired insulin secretion and insulin resistance, which are the two major pathologic factors for type 2 DM, and is also expected to increase adherence to treatment. We conducted a multicenter open-label prospective study to examine the usefulness of this CD for routine management of type 2 DM. METHODS: In type 2 DM patients with poor glycemic control who had been taking a DPP4I for ≥ 1 month, PG (15 mg/day) was added (first point). When the safety of PG was confirmed after 1 - 3 months, the DPP4I and PG were switched to the CD containing AG (25 mg) and PG (15 mg) (second point). Three months after switching to the CD was defined as the final point. Evaluation of objective findings, laboratory test results, and medication adherence was performed at these three points. RESULTS: Nineteen subjects completed the study, but this was far short of the target (160 subjects). Compared to the first point, white blood cell count (WBC), aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-glutamyl transpeptidase (γ-GTP), and fasting blood glucose (FBG) all showed a significant decrease at both the second and final points. No change in medication adherence was observed throughout the study period. The most notable point about this study was the extremely small number of subjects enrolled. As a possible explanation, we considered whether the preferences of the study doctors for antidiabetic drugs differed between specialties. The study doctors were mainly gastroenterologists, followed by endocrinologists/diabetologists and cardiologists in equal numbers. As an additional investigation, we determined the percentages of specialist doctors prescribing DPP4Is, sodium-glucose cotransporter-2 inhibitors (SGLT2Is), PG, or biguanides (BGs) as the main treatment for DM in 1 month at our hospital. We found that a low percentage of endocrinologists/diabetologists prescribing PG compared to other drugs, while cardiologists prescribed PG frequently. CONCLUSIONS: It was confirmed that the combination of DPP4I with PG was effective for the treatment of type 2 DM and improving metabolic function. Our data also showed that prescription of antidiabetic drugs differed between specialties, suggesting differences in their response to the results of various clinical studies and adverse reaction reports.

Design and Evaluation of An Extended-Release Olmesartan Tablet Using Chitosan/Cyclodextrin Composites.

Sustained-release olmesartan tablets (OLM) were prepared by the simple, direct compression of composites of anionic sulfobutyl ether-ß-cyclodextrin (SBE-ß-CD) and cationic spray-dried chitosan (SD-CS), and were evaluated for use as a sustained release preparation for the treatment of hypertension. An investigation of the interaction between OLM and SBE-ß-CD by the solubility method indicated that the phase diagram of the OLM/SBE-ß-CD system was the AL type, indicating the formation of a 1:1 inclusion complex. The release of OLM from tablets composed of the SD-CS/SBE-ß-CD composite was slow in media at both pH 1.2 and at 6.8. The in vitro slow release characteristics of the SD-CS/SBE-ß-CD composite were reflected in the in vivo absorption of the drug after normal rats were given an oral administration of the preparation. Furthermore, the SD-CS/SBE-ß-CD composite continuously increased the antihypertensive effect of OLM in hypertensive rats, compared with that of the drug itself. These results suggest that a simple mixing of SD-CS and SBE-ß-CD can be potentially useful for the controlled release of a drug for the continuous treatments of hypertension.

Preparation and evaluation of freeze dried surface-deacetylated chitin nanofiber/sacran pellets for use as an extended-release excipient.

Pelleted preparations were formulated from sacran (Sac), an anionic, sulfated, carboxyl-containing polysaccharide, which is extracted from the Japanese indigenous cyanobacterium Aphanothece sacrum, and surface-deacetylated chitin nanofibers (SDACNF). The use of this material as an extended-release excipient for tetrahydrocurcumin (THC), a model drug that is used to treat wounds via its radical scavenging ability was examined. The THC used in the study was complexed with 2-hydroxypropyl-ß-cyclodextrin (HP-ß-CD), which increases its water solubility. The radical scavenging activity of the THC/HP-ß-CD complex (molar ratio of 1:1) was significantly higher than the values for SDACNF or Sac alone. The rate of release of THC from the Sac/SDACNF pellets containing the THC/HP-ß-CD complex decreased with increasing Sac content in the pellet, suggesting that Sac/SDACNF (1:1) and Sac alone pellets function as extended-release excipients for THC. The findings reported here indicate that this can be attributed to the ability of the Sac component to retain fluids, thus extending the effects of the drug. In view of the above experimental outcomes, i.e. wound healing efficacy, fluid absorption, retention and the extended drug release of the system indicates that this preparation, in the appropriate ratios, has the potential for use as a controlled-release drug in wound healing.

Association between medication adherence and illness perceptions in atrial fibrillation patients treated with direct oral anticoagulants: An observational cross-sectional pilot study.

OBJECTIVE: The aim of this study was to examine the association between medication adherence and illness perceptions, and to explore the factors associated with poor medication adherence in atrial fibrillation (AF) patients receiving direct oral anticoagulants (DOACs) in a real-world clinical setting. METHODS: An observational cross-sectional pilot study was conducted at a single Japanese university hospital. One hundred and twenty-nine patients who were diagnosed with AF and who were taking DOACs were recruited from outpatients between January 4th and April 25th, 2017. We evaluated medication adherence to DOACs using the Morisky Medication Adherence Scale-8 (MMAS-8) and illness perceptions using the Brief Illness Perception Questionnaire (BIPQ). The patients' characteristics and clinical data were collected from electronic medical records. RESULTS: Ninety-nine (76.7%) patients (male, n = 74; mean age, 71.4±9.8 years) participated in this study. According to the MMAS-8, 21 (21.2%) of the patients were classified into the poor adherence group (MMAS-8 score of <6), and 78 (78.8%) were classified into the good adherence group (MMAS-8 score of 6-8). A multivariate logistic regression analysis revealed that age (per year, odds ratio [OR] 0.912, 95% confidence interval [CI] 0.853-0.965, p = 0.001), a history of warfarin use (OR 0.181, 95% CI 0.033-0.764, p = 0.019), duration of DOAC exposure (per 100 days, OR 1.245, 95% CI 1.084-1.460, p = 0.001), and the BIPQ emotional response score (per 1 point, OR 1.235, 95% CI 1.015-1.527, p = 0.035) were significantly associated with poor medication adherence in AF patients receiving DOACs. CONCLUSION: Poor medication adherence to DOACs was strongly associated with a stronger emotional response (i.e. stronger feelings of anger, anxiety, and depression), as well as younger age, the absence of a history of warfarin treatment, and longer DOAC exposure. Further evaluation of the factors associated with medication adherence in AF patients and the development and execution of strategies for improving poor adherence are warranted in the real-world clinical setting.

Urinary fibrin/fibrinogen degradation products measured using an anti-fibrinogen antibody predict orthostatic proteinuria.

BACKGROUND: The aim of this study was to assess the diagnostic value of urinary fibrin/fibrinogen degradation products (uFDP) measured using an anti-fibrinogen antibody in patients with orthostatic proteinuria (OP), and their use in differentiating between OP and glomerulonephritis (GN). METHODS: uFDP were measured using first urine in the morning (supine) and non-first urine during a hospital visit (upright) and then normalized to urine creatinine (uFDP/Cr, ng/mgCr). We compared (i) OP patients (n = 16); (ii) those in remission from nephrotic syndrome (NS, n = 14) and from GN (IgA nephropathy [IgAN], n = 14; Henoch-Schönlein purpura nephritis [HSPN], n = 12); and (iii) those with active GN (IgAN, n = 12; HSPN, n = 19). RESULTS: The uFDP/Cr ratio increased from supine to upright urine in patients with OP (P < 0.001), but decreased in one case. uFDP were excreted in supine urine in 94% of OP patients, with no excretion in NS remission patients or in 92% of GN remission patients (P < 0.001 for both). uFDP/Cr in supine urine was similar between the OP and active GN patients (P = 0.40), whereas proteinuria in supine urine was in the normal range in all OP patients, but was significantly higher in upright urine in the OP patients (P < 0.001). In upright urine, urinary protein/creatinine ratio was significantly lower in patients with OP than in those with active GN (P = 0.005). A uFDP/Cr ratio cut-off of 1,108 ng/mgCr in upright urine correctly differentiated OP from active GN, with a sensitivity of 87.5% and a specificity of 100%. CONCLUSION: Comparison of uFDP levels in supine/upright urine can be reliable for diagnosing OP and for differentiating it from active GN.

Strategies to encourage physical activity in patients with hemophilia to improve quality of life.

Hemophilia is a bleeding disorder caused by a congenital abnormality of blood coagulation. Until the mid-1970s, patients with hemophilia (PWH) were advised to refrain from physical activity (PA) because of a perceived increased risk of bleeding. Since then, PA, which is recognized as being essential for health maintenance, is now recommended by the World Federation of Hemophilia. Moreover, a number of studies reported that PA can improve treatment efficacy and prevent bleeding in PWH. Physical assessment and intervention in PA are currently used in clinical practice. However, the necessity of PA is not emphasized, and many PWH generally have low- to- no PA. Therefore, a behavior change approach to encourage patient motivation is becoming ever more important. In this article, we review articles addressing PA in PWH and discuss strategies to encourage PA through a behavior change approach by focusing on factors relevant to hemophilia, such as benefits and bleeding risk of PA, risk management of bleeding, PA characteristics, and difficulty with exercise adherence. The trust relationship between clinicians and patients, a transtheoretical model of behavior change, and motivation theory as approaches to promote PA are introduced. Finally, we review a case report of the clinical success of a behavior change approach to promote PA. Many PWH find it difficult to continue PA because of aging, fear of bleeding, insufficient recognition of PA benefits, and psychological problems. Therefore, it is essential and important to perform prophylaxis with PWH and to heighten their understanding of the benefits and risks of PA, before initiating the exercise regimen. For those patients who find it difficult to participate in PA, it is necessary to plan individual-based behavior change approach and encourage self-efficacy.

High-Contrast Imaging of Intermediate-Mass Giants with Long-Term Radial Velocity Trends.

A radial velocity (RV) survey for intermediate-mass giants has been operated for over a decade at Okayama Astrophysical Observatory (OAO). The OAO survey has revealed that some giants show long-term linear RV accelerations (RV trends), indicating the presence of outer companions. Direct imaging observations can help clarify what objects generate these RV trends. We present the results of high-contrast imaging observations of six intermediate-mass giants with long-term RV trends using the Subaru Telescope and HiCIAO camera. We detected co-moving companions to γ Hya B ( 0.61 - 0.14 + 0.12 M ⊙ ) , HD 5608 B (0.10 ± 0.01M ⊙), and HD 109272 B (0.28 ± 0.06M ⊙). For the remaining targets(ι Dra, 18 Del, and HD 14067) we exclude companions more massive than 30-60 M Jup at projected separations of 1''-7''. We examine whether these directly imaged companions or unidentified long-period companions can account for the RV trends observed around the six giants. We find that the Kozai mechanism can explain the high eccentricity of the inner planets ι Dra b, HD 5608 b, and HD 14067 b.

Near-infrared imaging polarimetry of LkCa 15: A possible warped inner disk.

We present high-contrast H-band polarized intensity images of the transitional disk around the young solar-like star LkCa 15. By utilizing Subaru/HiCIAO for polarimetric differential imaging, the angular resolution and the inner working angle reach 0.07 and r = 0″.1, respectively. We obtained a clearly resolved gap (width ≲ 27 au) at ~48 au from the central star. This gap is consistent with images reported in previous studies. We also confirmed the existence of a bright inner disk with a misaligned position angle of 13° ±4° with respect to that of the outer disk, i.e., the inner disk is possibly warped. The large gap and the warped inner disk both point to the existence of a multiple planetary system with a mass of ≲ 1 M Jup.

Joint Function and Arthropathy Severity in Patients with Hemophilia.

BACKGROUND: The Arnold-Hilgartner classification is one of the most popular evaluation systems for the progression hemophilic arthropathy. A previous study reported an association between arthropathy severity and arc range of motion (ROM). However, associations between arthropathy severity and angular ROM and muscle strength remain unclear. AIM: The purpose of this study was to clarify the association between joint function and arthropathy severity in hemophilia. METHODS: We studied the knee, ankle, and elbow joints of 31 patients with hemophilia (PWH). The condition of the affected joints was evaluated on the basis of the interview data, joint function measurements, and roentgenography of the affected joints. In assessment of joint function, we evaluated knee strength (flexor, extensor) and grip strength as well as the passive ROM of the elbow, knee, and ankle. During the interview, all patients were asked about the history of intra-articular bleeding over the past year and pain. RESULTS: As arthropathy severity worsened, knee flexor strength, knee extensor strength, grip strength, and ROM (elbow flexion, elbow extension, knee flexion, knee extension, and ankle extension) significantly decreased. Even patients with mild arthropathies experienced knee extensor weakness and extension limitation. In addition, joint function of severe ankle arthropathy was significantly related to the history of intra-articular bleeding and pain. CONCLUSION: Our results suggest that physical therapy is necessary to improve joint function in PWH and mild or no arthropathy. Pain control and prophylactic hematological management are necessary for patients with severe arthropathy because intra-articular bleeding and pain significantly decrease joint function.

H3(+) spectroscopy and the ionization rate of molecular hydrogen in the central few parsecs of the galaxy.

We report observations and analysis of infrared spectra of H3(+) and CO lines in the Galactic center, within a few parsecs of the central black hole, Sgr A*. We find a cosmic ray ionization rate typically an order of magnitude higher than outside the Galactic center. Notwithstanding, the elevated cosmic ray ionization rate is 4 orders of magnitude too short to match the proton energy spectrum, as inferred from the recent discovery of the TeV γ-ray source in the vicinity of Sgr A*.

The renin-angiotensin system and hypertension in autosomal recessive polycystic kidney disease.

Hypertension is a well-recognized complication of autosomal recessive polycystic kidney disease (ARPKD). The renin-angiotensin system (RAS) is a key regulator of blood pressure; however, data on the RAS in ARPKD are limited and conflicting, showing both up- and down-regulation. In the current study, we characterized intrarenal and systemic RAS activation in relationship to hypertension and progressive cystic kidney disease in the ARPKD orthologous polycystic kidney (PCK) rat. Clinical and histological measures of kidney disease, kidney RAS gene expression by quantitative real-time PCR, angiotensin II (Ang II) immunohistochemistry, and systemic Ang I and II levels were assessed in 2-, 4-, and 6-month-old cystic PCK and age-matched normal rats. PCK rats developed hypertension and progressive cystic kidney disease without significant worsening of renal function or relative kidney size. Intrarenal renin, ACE and Ang II expression was increased significantly in cystic kidneys; angiotensinogen and Ang II Type I receptor were unchanged. Systemic Ang I and II levels did not differ. This study demonstrates that intrarenal, but not systemic, RAS activation is a prominent feature of ARPKD. These findings help reconcile previous conflicting reports and suggest that intrarenal renin and ACE gene upregulation may represent a novel mechanism for hypertension development or exacerbation in ARPKD.