FHL2 in arterial medial calcification in chronic kidney disease.

BACKGROUND AND HYPOTHESIS: Arterial medial calcification (AMC) is a common complication in individuals with chronic kidney disease (CKD), which can lead to cardiovascular morbidity and mortality. The progression of AMC is controlled by a key transcription factor called runt-related transcription factor 2 (RUNX2), which induces vascular smooth muscle cells (VSMCs) transdifferentiation into a osteogenic phenotype. However, RUNX2 has not been targeted for therapy due to its essential role in bone development. The objective of our study was to discover a RUNX2 coactivator that is highly expressed in arterial VSMCs as a potential therapy for AMC. METHODS: We employed transcriptomic analysis of human data and an animal reporter system to pinpoint FHL2 as a potential target. Subsequently, we investigated the mRNA and protein expression patterns of FHL2 in the aortas of both human and animal subjects with CKD. To examine the role of FHL2 in the RUNX2 transcription machinery, we conducted coimmunoprecipitation (Co-IP) and chromatin immunoprecipitation (ChIP) experiments. Next, we manipulated FHL2 expression in cultured VSMCs to examine its impact on high phosphate-induced transdifferentiation. Finally, we employed FHL2 null mice to confirm the role of FHL2 in the development of AMC in vivo. RESULTS: Among all the potential RUNX2 cofactor, FHL2 displays selective expression within the cardiovascular system. In the context of CKD subjects, FHL2 undergoes upregulation and translocation from the cytosol to the nucleus of arterial VSMCs. Once in the nucleus, FHL2 interacts structurally and functionally with RUNX2, acting as a coactivator of RUNX2. Notably, the inhibition of FHL2 expression averts transdifferentiation of VSMCs into an osteogenic phenotype and mitigates aortic calcification in uremic animals, without causing any detrimental effects on the skeletal system. CONCLUSION: These observations provide evidence that FHL2 is a promising target for treating arterial calcification in patients with CKD.

Associations of urinary fetuin-A with histopathology and kidney events in biopsy-proven kidney disease.

Background: Fetuin-A is implicated in the pathogenesis of vascular calcification in chronic kidney disease (CKD); however, the relationship between fetuin-A, histopathologic lesions and long-term kidney outcomes in patients with various types of kidney disease remains unclear. Methods: We measured urinary fetuin-A levels in 335 individuals undergoing clinically indicated native kidney biopsy. The expressions of fetuin-A mRNA and protein in the kidney were assessed using RNA sequencing and immunohistochemistry. The association of urinary fetuin-A with histopathologic lesions and major adverse kidney events (MAKE), defined as a decline in estimated glomerular filtration rate (eGFR) of at least 40%, kidney failure or death, was analyzed. Results: Urinary fetuin-A levels showed a positive correlation with albuminuria (rs = 0.67, P < .001) and a negative correlation with eGFR (rs = -0.46, P < .001). After multivariate adjustment, higher urinary fetuin-A levels were associated with glomerular inflammation, mesangial expansion, interstitial fibrosis and tubular atrophy, and arteriolar sclerosis. Using a 1 transcript per million gene expression cutoff, we found kidney fetuin-A mRNA levels below the threshold in both individuals with normal kidney function and those with CKD. Additionally, immunohistochemistry revealed reduced fetuin-A staining in tubular cells of CKD patients compared with normal controls. During a median 21-month follow-up, 115 patients experienced MAKE, and Cox regression analysis confirmed a significant association between elevated urinary fetuin-A and MAKE. This association remained significant after adjusting for potential confounding factors. Conclusion: Urinary fetuin-A is associated with chronic histological damage and adverse clinical outcomes across a spectrum of biopsy-proven kidney diseases.

How renal toxins respond to renal function deterioration and oral toxic adsorbent in pH-controlled releasing capsule.

The number of patients with chronic kidney disease (CKD) is increasing. Oral toxin adsorbents may provide some value. Several uremic toxins, including indoxyl sulfate (IS), p-cresol (PCS), acrolein, per- and poly-fluoroalkyl substances (PFAS), and inflammation markers (interleukin 6 [IL-6] and tumor necrosis factor [TNF]-alpha) have been shown to be related to CKD progression. A total of 81 patients taking oral activated charcoal toxin adsorbents (AC-134), which were embedded in capsules that dissolved in the terminal ileum, three times a day for 1 month, were recruited. The renal function, hemoglobulin (Hb), inflammation markers, three PFAS (PFOA, PFOS, and PFNA), and acrolein were quantified. Compared with the baseline, an improved glomerular filtration rate (GFR) and significantly lower acrolein were noted. Furthermore, the CKD stage 4 and 5 group had significantly higher concentrations of IS, PCS, IL-6, and TNF but lower levels of Hb and PFAS compared with the CKD Stage 3 group at baseline and after the intervention. Hb was increased only in the CKD Stage 3 group after the trial (p = .032). Acrolein did not differ between the different CKD stage groups. Patients with improved GFR (responders) (about 77%) and nonresponders had similar baseline GFR. Responders had higher acrolein and PFOA levels throughout the study and a more significant reduction in acrolein, indicating a better digestion function. Responders had higher acrolein and PFOA levels throughout the study and a more significant reduction in acrolein, while PFOA increased in responders. Both the higher PFOA and lower acrolein may be related to improved eGFR (and possibly to improvements in proteinuria, which we did not measure. Proteinuria is associated with PFAS loss in the urine), AC-134 showed the potential to improve the GFR and decrease acrolein, which might better indicate renal function change. Future studies are needed with longer follow-ups.

Unusual Coincidence: Concurrent Cast Nephropathy and Lymphoma Infiltration in an Influenza A-Associated Acute Kidney Injury.

Acute kidney injury (AKI) poses a substantial challenge in the management of lymphoma patients and is frequently associated with diverse causative factors. Herein, we report an illustrative case involving a 47-year-old male with influenza A infection who developed severe AKI, which was incongruent with his medical history. Laboratory investigations disclosed aberrant immunoglobulin levels and urinary protein excretion, prompting further evaluation. A renal biopsy revealed the presence of infiltrating lymphoid cells and cast nephropathy, raising suspicion of an underlying hematological disorder. A comprehensive diagnostic workup, including positron emission tomography imaging and bone marrow biopsy, culminated in the definitive diagnosis of splenic marginal zone lymphoma. This case highlights the crucial significance of including lymphoma-associated kidney disorders in the evaluation of unexplained AKI, particularly when encountering unconventional clinical and laboratory results. Swift and precise intervention is of utmost importance in attaining positive results in these rare and complex clinical situations. This study underscores the persistent concern of AKI in lymphoma patients, with lymphocytic infiltration and cast nephropathy as notable elements contributing to the intricate nature of this condition.

Comparative analysis of hemodialysis and peritoneal dialysis on the risk of new onset diabetes mellitus.

BACKGROUND: Diabetes mellitus is a significant risk factor for cardiovascular events and mortality in dialysis patients. The impact of different dialysis modalities on the risk of new onset diabetes mellitus (NODM) remains a subject of debate. Previous studies did not adequately account for critical confounding factors such as pre-dialysis glycemic status, medication use, and nutritional status, which may influence the association between dialysis modality and NODM risk. METHODS: We conducted a retrospective cohort study of 1426 non-diabetic end-stage renal disease (ESRD) patients who underwent either hemodialysis (HD) or peritoneal dialysis (PD) at a single medical center. We used different statistical methods, adjusting for potential confounding factors, and accounted for competing risk of death. RESULTS: Over 12 years, 331 patients (23 %) developed NODM. After adjusting for potential confounding factors and mortality, PD patients had a significantly higher risk of NODM compared to HD patients (adjusted HR 1.52, p = 0.001). A propensity-matched cohort sensitivity analysis yielded similar results. Among patients with prediabetes, those receiving PD had a 2.93 times higher risk of developing NODM than those receiving HD (p for interaction <0.001), whereas no significant difference was observed among euglycemic patients. NODM was also associated with a 1.78 times increased risk of major cardiovascular events. CONCLUSION: Our study provides evidence that PD treatment may increase the risk of NODM in ESRD patients, particularly among those with preexisting prediabetes. These findings highlight the importance of personalized treatment approaches, and nephrologists should consider prediabetes when choosing the dialysis modality for their patients.

Circulating Activin A, Kidney Fibrosis, and Adverse Events.

BACKGROUND: Identification of reliable biomarkers to assess kidney fibrosis severity is necessary for patients with CKD. Activin A, a member of the TGF- ß superfamily, has been suggested as a biomarker for kidney fibrosis. However, its precise utility in this regard remains to be established. METHODS: We investigated the correlation between plasma activin A levels, kidney fibrosis severity, and the incidence of major adverse kidney events in patients who underwent native kidney biopsies at a tertiary medical center. We performed RNA sequencing and histological analyses on kidney biopsy specimens to assess activin A expression. In vitro experiments were also conducted to explore the potential attenuation of TGF- ß -induced fibroblast activation through activin A inhibition. RESULTS: A total of 339 patients with biopsy-confirmed kidney diseases were enrolled. Baseline eGFR was 36 ml/min per 1.73 m 2 , and the urine protein/creatinine ratio was 2.9 mg/mg. Multivariable logistic regression analysis revealed a significant association between plasma activin A levels and the extent of tubulointerstitial fibrosis. Our RNA sequencing data demonstrated a positive correlation between kidney INHBA expression and plasma activin A levels. Furthermore, the histological analysis showed that myofibroblasts were the primary activin A-positive interstitial cells in diseased kidneys. During a median follow-up of 22 months, 113 participants experienced major adverse kidney events. Cox proportional hazards analysis initially found a positive association between plasma activin A levels and kidney event risk, but it became insignificant after adjusting for confounders. In cultured fibroblasts, knockdown of activin A significantly attenuated TGF- ß -induced fibroblast-myofibroblast conversion. CONCLUSIONS: Plasma activin A levels correlate with kidney fibrosis severity and adverse outcomes in various kidney disorders.

Survival benefit of a third dose of the COVID-19 vaccine among hemodialysis patients: A prospective cohort study.

BACKGROUND: Hemodialysis (HD) patients are particularly vulnerable to severe coronavirus disease 2019 (COVID-19) due to their immunocompromised state and comorbid conditions. Timely vaccination could be the most effective strategy to reduce morbidity and mortality. However, data on the survival benefit of the COVID-19 vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and death among HD patients are limited, especially during the Omicron-dominant period. METHODS: In this prospective hospital-based cohort study, we identified HD patients from July 1, 2021, to April 29, 2022. The patients were divided into fully vaccinated and partially vaccinated groups. We compared the humoral response, risk of developing SARS-CoV-2 infection, and all-cause mortality between the two groups. RESULTS: Among the 440 HD patients included, 152 patients were fully vaccinated, and 288 patients were partially vaccinated. Patients in the fully vaccinated group exhibited higher anti-spike protein receptor-binding domain (S protein RBD) antibody levels and lower risks of all-cause mortality (adjusted hazard ratio, 0.35; 95% confidence interval, 0.17-0.73; p = 0.005) than the partially vaccinated group. However, the risk for SARS-CoV-2 infection did not significantly differ between the two groups. Irrespective of the number of vaccinations, the risk of all-cause mortality was lower in patients with anti-S protein RBD antibody levels in the higher tertile. CONCLUSION: A third dose of the COVID-19 vaccine was associated with a decreased risk of all-cause mortality among HD patients during the Omicron-dominant period. A higher post-vaccination anti-S protein RBD antibody level was also associated with a lower risk of mortality.

Key pathological features characterize minimal change disease-like IgA nephropathy.

AIMS: A subset of IgA nephropathy (IgAN) patients exhibiting minimal change disease (MCD) like features present with nephrotic-range proteinuria and warrants immunosuppressive therapy (IST). However, the diagnosis of MCD-like IgAN varied by reports. We aimed to identify the key pathological features of MCD-like IgAN. METHODS: In this cohort, 228 patients had biopsy-proven IgAN from 2009 to 2021, of which 44 without segmental sclerosis were enrolled. Patients were classified into segmental (< 50% glomerular capillary loop involvement) or global (> 50%) foot process effacement (FPE) groups. We further stratified them according to the usage of immunosuppressant therapy after biopsy. Clinical manifestations, treatment response, and renal outcome were compared. RESULTS: 26 cases (59.1%) were classified as segmental FPE group and 18 cases (40.9%) as global FPE group. The global FPE group had more severe proteinuria (11.48 [2.60, 15.29] vs. 0.97 [0.14, 1.67] g/g, p = 0.001) and had a higher proportion of complete remission (81.8% vs. 20%, p = 0.018). In the global FPE group, patients without IST experienced more rapid downward eGFR change than the IST-treated population (-0.38 [-1.24, 0.06] vs. 1.26 [-0.17, 3.20]mL/min/1.73 m2/month, p = 0.004). CONCLUSIONS: The absence of segmental sclerosis and the presence of global FPE are valuable pathological features that assist in identifying MCD-like IgAN.

Hybrid Method for Peritoneal Dialysis Catheter Insertion: A New Technique for Improved Outcomes and Reduced Costs.

INTRODUCTION: Peritoneal dialysis (PD) is a well-established treatment choice for end-stage kidney disease (ESKD). While there are several methods for PD catheter insertion, they each have limitations. In this study, we present a new hybrid method for PD catheter insertion and compare it to the conventional laparoscopic method. METHODS: This retrospective study included 171 patients who were undergoing their first PD catheter insertion, and a total of 20% of the enrolled patients had a past medical history of abdominal surgery. Out of these, 101 patients underwent the laparoscopic method and 70 underwent a new invented hybrid method. The study aimed to compare the surgical outcomes, incidence of early and late complications, hospital stay, and medical expenses between the two groups. RESULTS: There were no notable differences in basic demographic features and comorbid conditions between the two groups. The results of our data revealed that the hybrid group had a significantly shorter break-in period and did not require temporary hemodialysis. Additionally, length of hospital stay and medical costs were significantly lower in the hybrid group (all p < 0.05). The incidence of early complications was lower in the hybrid group, while the incidence of late complications was comparable between the two groups. CONCLUSION: Our study demonstrates that the hybrid method of PD catheter insertion provides a safe and efficient alternative to the traditional laparoscopic method, enabling urgent-start PD and reducing hospital stays and medical expenses. Our findings support the use of the hybrid method as a new standard of care for ESKD patients undergoing PD catheter insertion.

Macrophage inflammatory protein-1ß as a novel therapeutic target for renal protection in diabetic kidney disease.

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease worldwide and the prevalence of DKD has increased over recent decades. Inflammation is involved in the development and progression of DKD. In this study, we explored the potential role of macrophage inflammatory protein-1ß (MIP-1ß) in DKD. Clinical non-diabetic subjects and DKD patients with different levels of urine albumin-to-creatinine ratio (ACR) were enrolled in the study. Leprdb/db mice and MIP-1ß knockout mice were also used as mouse models for DKD. We found that serum MIP-1ß levels were elevated in the DKD patients, especially those with ACRs that were less than or equal to 300, suggesting that MIP-1ß is activated in clinical DKD. The administration of anti-MIP-1ß antibodies attenuated DKD severity in the Leprdb/db mice, which also showed reduced glomerular hypertrophy and podocyte injury, as well as decreased inflammation and fibrosis, suggesting that MIP-1ß plays a role in the development of DKD. The MIP-1ß knockout mice showed improved renal function and decreased renal glomerulosclerosis and fibrosis in DKD. Furthermore, podocytes from the MIP-1ß knockout mice showed less high glucose-induced inflammation and fibrosis compared to those from wild-type mice. In conclusion, the inhibition or deletion of MIP-1ß protected podocytes, modulated renal inflammation, and ameliorated experimental DKD, suggesting that novel anti-MIP-1ß strategies could potentially be used to treat DKD.

The Associations between Erythropoietic Response with Inflammation Markers and Perfluorinated Chemicals in Hemodialysis Patients.

Erythropoiesis-stimulating agents (ESA) are used to treat anemia in hemodialysis (HD) patients. We investigated the role of inflammation and accumulation of environmental toxins (perfluorinated chemicals (PFCs), such as perfluorooctanoic acid and perfluorooctane sulfonate) in the erythropoietic response of HD patients who receive a fixed monthly continuous erythropoietin receptor activator (CERA) dosage. Forty-five patients underwent three successive phases of ESA treatment for two months each (phase one: 100 µg CERA once monthly; phase two: 50 µg CERA twice monthly; phase three: 100 µg CERA once monthly). Patient data were collected to determine the association of various factors with erythropoietic response (change in hematocrit). Liquid chromatography-tandem mass spectrometry was used to analyze perfluorinated chemicals. Twenty-eight patients exhibited a poor erythropoietic response that was significantly associated with: age > 80 years, initial hematocrit > 36%, glucose > 200 mg/dL, alanine aminotransferase > 21 U/L, c-reactive protein > 1 mg/dL, interleukin-6 > 10 ng/mL, lactate dehydrogenase ≤ 190 U/L, and chloride ≤ 93 mEq/L. There was also a borderline significant association between inflammation and PFCs, although PFCs failed to show any impact on ESA response. Age, glucose, chloride, liver function, and inflammation may be associated with cost-effective fixed CERA dosage administered at an increased frequency.

Double Filtration Plasmapheresis with Polyvinyl Alcohol-Based Membrane Lowers Serum Inflammation and Toxins in Patients with Hyperlipidemia.

Hyperlipidemia is increasing in prevalence and is highly correlated with cardiovascular disease (CVD). Lipid-lowering medications prevent CVD but may not be suitable when the side effects are intolerable or hypercholesterolemia is too severe. Double-filtration plasmapheresis (DF) has shown its therapeutic effect on hyperlipidemia, but its side effects are not yet known. We enrolled 45 adults with hyperlipidemia in our study. The sera before and two weeks after DF were evaluated, and we also analyzed perfluorochemicals to see if DF could remove these lipophilic toxins. After DF, all lipid profile components (total cholesterol, triglycerides, high-density lipoprotein [HDL], and low-density lipoprotein [LDL]) had significantly decreased. Leukocyte counts increased while platelet levels decreased, which may have been caused by the puncture wound from DF and consumption of platelets during the process. As for uremic toxins and inflammation, levels of C-reactive protein, uric acid, and alanine transaminase (ALT) all decreased, which may be related to the removal of serum perfluorooctane sulfonate (PFOS) and improvement of renal function. The total cholesterol/HDL ratio and triglycerides were significantly higher in the diabetes mellitus (DM) group at baseline but did not significantly differ after DF. In conclusion, DF showed potential for improving inflammation and removing serum lipids and PFOS in adults with hyperlipidemia.

The Effects of Yoga Exercise on Blood Pressure and Hand Grip Strength in Chronic Stroke Patients: A Pilot Controlled Study.

BACKGROUND: We investigated the beneficial effect of add-on yoga with rehabilitation on blood pressure (BP) and hand grip strength in patients with chronic stroke (more than 90 days). METHODS: The study included patients 30-80 years of age who could stand independently for 1 min. Patients with psychiatric diseases or undergoing other therapies (like acupuncture) were excluded. The yoga group received training (1 h session twice weekly) with standard rehabilitation for 8 weeks. The control group received standard rehabilitation only. There were no differences in age, gender, hand grip strength, or BP between the two groups (16 subjects in each group) at baseline. RESULTS: The systolic BP (p = 0.01) decreased significantly, and the diastolic BP also decreased but not significantly in the yoga group (p = 0.11). For hand grip strength, both the unaffected hand (p = 0.00025) and the affected hand (p = 0.027) improved significantly. The control group showed no significant change in systolic or diastolic BP, nor did the grip strength change in both hands. Gender and age also affected the results of overall rehabilitation in that women benefited more from a decrease in BP, while men and young people (lower than the mean age of 60) benefited from hand grip strength improvement. CONCLUSIONS: Combining yoga with rehabilitation in chronic stroke patients can improve hand grip strength and decrease systolic BP.

Sacubitril/Valsartan in Patients With Heart Failure and Concomitant End-Stage Kidney Disease.

Background Heart failure with reduced ejection fraction (HFrEF) is a chronic disease with substantial mortality. Management of HFrEF has seen significant breakthrough after the launch of neprilysin inhibitor. The PARADIGM-HF (Prospective Comparison of ARNI with ACEI to Determine Impacton Global Mortality and Morbidity in Heart Failure) trial showed that sacubitril/valsartan significantly reduces HFrEF mortality and the heart failure hospitalization rate. However, in patients with advanced kidney disease, who have the highest prevalence of heart failure, the efficacy and safety of sacubitril/valsartan remains uncertain. We aim to study the efficiency of sacubitril/valsartan in patients with end-stage kidney disease. Methods and Results Heart function was screened by echocardiogram among all patients with end-stage kidney disease in 2 hospitals. Patients with HFrEF received either sacubitril/valsartan or conventional treatment. Fifteen echocardiographic parameters were compared before and after treatment. After 1-year sacubitril/valsartan treatment, parameters of systolic (left ventricular ejection fraction 31.3% to 45.1%, P<0.0001; left ventricular end-systolic volume 95.7 to 70.1 mL, P=0.006; left ventricular internal diameter at end-systole phase 47.2 to 40.1 mm, P=0.005), and diastolic (E/A ratio 1.3 to 0.8, P=0.009; E/Med e' ratio 25.3 to 18.8, P=0.010) function improved in patients with HFrEF and end-stage kidney disease. These parameters were unchanged in the conventional treatment group. Serum potassium did not increase in the sacubitril/valsartan group. Conclusions Sacubitril/valsartan improves left ventricular systolic and diastolic function in patients with HFrEF and end-stage kidney disease.

Perfluorooctanesulfonate Can Cause Negative Bias in Creatinine Measurement in Hemodialysis Patients Using Polysulfone Dialysis Membranes.

Serum creatinine is an important clinical marker for renal clearance. However, two conventional methods (Jaffe and enzymatic) are prone to interferences with organic compounds as compared to the standard method (isotope dilution-liquid chromatography-mass spectrometry) and can cause a significant negative bias. Perfluorooctanesulfonate (PFOS) and perfluorooctanoic acid (PFOA) are two common perfluorochemicals (PFCs) that can easily be accumulated in humans. We aimed to verify whether this bias is the result of an accumulation of PFCs. The serum creatinine values of 124 hemodialysis patients were analyzed using the three methods. We also aimed to evaluate which biochemical parameters will influence the difference between the conventional methods and the standard method. We found that a significant underestimation occurred when using the conventional methods. Albumin is an independent factor associated with negative bias, but it loses this correlation after dialysis, likely due to the removal of protein-bound uremic toxins. PFOS can cause negative bias when using the enzymatic method. Furthermore, this linear correlation is more significant in patients who used polysulfone-based dialysis membranes, possibly due to the better clearance of other uremic toxins. The serum creatinine of uremic patients can be significantly underestimated when using conventional methods. PFCs, as well the type of dialysis membrane being used, can be influencing factors.

Far-Infrared Therapy Improves Arteriovenous Fistula Patency and Decreases Plasma Asymmetric Dimethylarginine in Patients with Advanced Diabetic Kidney Disease: A Prospective Randomized Controlled Trial.

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase and plays a significant role in the pathogenesis of arteriovenous fistula (AVF) dysfunction. The aim of this study is to evaluate the effect of far-infrared (FIR) therapy on the maturation and patency of newly-created AVFs in patients with advanced diabetic kidney disease (DKD) as well as the concurrent change in plasma ADMA. The study enrolled 144 participants with advanced DKD where 101 patients were randomly allocated to the FIR therapy group (N = 50) and control group (N = 51). Patients receiving FIR therapy had a decreased AVF failure rate within 12 months (16% versus 35.3%; p = 0.027); decreased incremental change of ADMA concentration at the 3rd and 12th month; increased AVF blood flow at the 1st, 3rd, and 12th month; increased 3-month physiologic maturation rate (88% versus 68.6%; p = 0.034); increased 1-year unassisted AVF patency rate (84% versus 64.7%; p = 0.017); and increased clinical AVF maturation rate within 12 months (84% versus 62.7%; p = 0.029) compared to the control group. The study demonstrates that FIR therapy can reduce the incremental changes in plasma ADMA concentration, which may be associated with the improvement of AVF prognosis in patients with advanced DKD.

Chronic Kidney Disease Is Associated With Increased Cardiac Corin Expression But Decreased Proatrial Natriuretic Peptide Conversion Activity.

Background Chronic kidney disease (CKD) is associated with an increased risk of cardiovascular disease. Corin converts proatrial natriuretic peptide into its active form after being activated by PCSK6 (proprotein convertase subtilisin/kexin type 6) protease. It remains unknown whether the PCSK6/corin/atrial natriuretic peptide pathway plays a role in CKD-induced cardiomyopathy. Methods and Results Serum corin, left ventricular mass index, and corin-left ventricular mass index correlation were compared between outpatients with versus without CKD. Cardiac corin expression and activity as well as serum corin were compared between 5/6 nephrectomy CKD animal models and sham controls. The effects of indoxyl sulfate, a uremic toxin, on cardiomyocytes were examined in vitro in H9c2 cells. A total of 543 patients were enrolled in this study. Serum corin levels were elevated in patients with CKD compared with levels in patients without CKD. Serum corin levels correlated negatively with left ventricular mass index in participants without CKD, but not in patients with CKD. Compared with sham controls, CKD mice had higher serum corin levels and increased cardiac expression of corin but reduced cardiac corin conversion activity. Indoxyl sulfate stimulated corin expression while suppressing serine protease activity in H9c2 cardiomyoblasts. Lower PCSK6 expression in CKD mouse hearts and indoxyl sulfate-treated H9c2 cardiomyoblasts may explain, at least partly, the observed CKD-associated reduction in corin activity. Conclusions In CKD, cardiac and serum levels of corin are increased, yet corin activity is suppressed. The latter may be attributable to reduced PCSK6 expression. These findings suggest that corin dysfunction may play a significant role in the pathogenesis of CKD-associated cardiomyopathy.

Baseline Peritoneal Membrane Transport Characteristics Are Associated with Peritonitis Risk in Incident Peritoneal Dialysis Patients.

The peritoneal equilibration test (PET) is a semi-quantitative measurement that characterizes the rate of transfer of solutes and the water transfer rate across the peritoneum in patients treated with peritoneal dialysis (PD). The results of the PET are used to maximize daily peritoneal ultrafiltration and solute clearances. Previous studies have shown that high transport status is associated with ultrafiltration failure, malnutrition, and reduced survival; however, the way in which peritoneum transport characteristics affect peritonitis risk is unknown. In the current cohort study, we recruited 898 incident-PD patients and used intention-to-treat analysis to test if baseline PET affected the subsequent 3-year peritonitis rate. Among all recruited PD patients, 308 (34.2%) developed peritonitis within three years. Multivariate Cox regression analysis showed that the high-transport group has the greatest peritonitis risk (HR 1.98, 95% CI: 1.08-3.62) even after an adjustment for demographics, comorbid diseases, and biochemical measurements. We concluded that a baseline high peritoneal membrane transport rate is an independent risk factor for peritonitis in incident PD patients.

Artificial Kidney Engineering: The Development of Dialysis Membranes for Blood Purification.

The artificial kidney, one of the greatest medical inventions in the 20th century, has saved innumerable lives with end stage renal disease. Designs of artificial kidney evolved dramatically in decades of development. A hollow-fibered membrane with well controlled blood and dialysate flow became the major design of the modern artificial kidney. Although they have been well established to prolong patients' lives, the modern blood purification system is still imperfect. Patient's quality of life, complications, and lack of metabolic functions are shortcomings of current blood purification treatment. The direction of future artificial kidneys is toward miniaturization, better biocompatibility, and providing metabolic functions. Studies and trials of silicon nanopore membranes, tissue engineering for renal cell bioreactors, and dialysate regeneration are all under development to overcome the shortcomings of current artificial kidneys. With all these advancements, wearable or implantable artificial kidneys will be achievable.

Peritoneal-Membrane Characteristics and Hypervolemia Management in Peritoneal Dialysis: A Randomized Control Trial.

Excessive bodily-fluid retention is the major cause of hypertension and congestive heart failure in patients with end-stage renal disease. Compared to hemodialysis, peritoneal dialysis (PD) uses the abdominal peritoneum as a semipermeable dialysis membrane, providing continuous therapy as natural kidneys, and having fewer hemodynamic changes. One major challenge of PD treatment is to determine the dry weight, especially considering that the speed of small solutes and fluid across the peritoneal membrane varies among individuals; considerable between-patient variability is expected in both solute transportation and ultrafiltration capacity. This study explores the influence of peritoneal-membrane characteristics in the hydration status in patients on PD. A randomized control trial compares the bioimpedance-assessed dry weight with clinical judgment alone. A high peritoneal membrane D/P ratio was associated with the extracellular/total body water ratio, dialysate protein loss, and poor nutritional status in patients on PD. After a six-month intervention, patients with monthly bioimpedance analysis (BIA) assistance had better fluid (-1.2 ± 0.4 vs. 0.1 ± 0.4 kg, p = 0.014) and blood-pressure (124.7 ± 2.7 vs. 136.8 ± 2.8 mmHg, p < 0.001) control; however, hydration status and blood pressure returned to the baseline after we prolonged BIA assistance to a 3-month interval. The dry-weight reduction process had no negative effect on residual renal function or peritoneal-membrane function. We concluded that peritoneal-membrane characteristics affect fluid and nutritional status in patients on PD, and BIA is a helpful objective technique for fluid assessment for PD.