Understanding the Korean dialysis cohort for mineral, vascular calcification, and fracture (ORCHESTRA) Study: Design, method, and baseline characteristics.

INTRODUCTION: End-stage renal disease (ESRD) is a growing disease in Korea and worldwide and is an important condition that affects patient outcomes. In order to provide optimal management for mineral disturbance, vascular calcification, and bone disease of ESRD patients, the ORCHESTRA study (Korean dialysis cohort for mineral, vascular calcification, and fracture) was conducted and enrolled Korean dialysis patients. METHODS: Sixteen university-affiliated hospitals and one Veterans Health Service Medical Center participated in this study. This prospective cohort study enrolled approximately 900 consecutive dialysis patients between May 2019 and January 2021. Enrolled subjects were evaluated at baseline for demographic information, laboratory tests, radiologic imaging, and bone mineral densitometry (BMD) scans. After enrollment, regular assessments of patients were performed and their biospecimens were collected according to the study protocol. Primary outcomes were occurrence of major adverse cardiovascular events (MACE), invasive treatment for peripheral artery disease (PAD), and osteoporotic fractures. Secondary outcomes were hospitalization for cerebro-cardiovascular disease or progression of abdominal aortic calcification (AAC). Participants will be assessed for up to three years to determine whether primary or secondary outcomes occur. RESULTS: From May 2019 to January 2021, all participating centers recruited 900 consecutive dialysis patients, including 786 undergoing hemodialysis (HD) and 114 undergoing peritoneal dialysis (PD). The mean age of subjects was 60.4 ± 12.3 years. Males accounted for 57.7%. The mean dialysis vintage was 6.1 ± 6.0 years. The HD group was significantly older, had a longer dialysis vintage, and more comorbidities. Overall, the severity of vascular calcification was higher and the level of BMD was lower in the HD group than in the PD group. CONCLUSION: This is a nationwide, multicenter, prospective cohort study that focuses on CKD-mineral and bone disorder (CKD-MBD) and aims to provide clinical evidence to establish optimal treatment guidelines for Asian dialysis patients.

Phosphodiesterase inhibitor ameliorates senescent changes of renal interstitial pericytes in aging kidney.

Pericytes are mesenchymal cells that surround endothelial cells, playing a crucial role in angiogenesis and vessel maturation. Additionally, they are associated with interstitial fibrosis as a major contributor to renal myofibroblasts. In this study, we aim to investigate whether the phosphodiesterase inhibitor, pentoxifylline (PTX), can ameliorate aging-related functional and histological deterioration in the kidney. We subjected aging C57BL/6 mice, dividing into young, aging, and PTX-treated aging groups. Renal function, albuminuria, and histological changes were assessed. Interstitial pericytes were assessed by immunohistochemistry analysis. We examined changes in pericytes in elderly patients using human kidney tissue obtained from healthy kidney donors for kidney transplantation. In vitro experiments with human pericytes and endothelial cells were performed. Aging mice exhibited declined renal function, increased albuminuria, and aging-related histological changes including mesangial expansion and tubulointerstitial fibrosis. Notably, number of pericytes declined in aging kidneys, and myofibroblasts increased. PTX treatment ameliorated albuminuria, histological alterations, and microvascular rarefaction, as well as modulated angiopoietin expression. In vitro experiments showed PTX reduced cellular senescence and inflammation. Human kidney analysis confirmed similar pericyte changes in aging kidneys. The phosphodiesterase inhibitor, PTX preserved microvascular density and improved renal interstitial fibrosis and inflammation in aging mice kidneys. These protective effects were suggested to be associated with the amelioration of pericytes reduction and the transition to myofibroblasts. Additionally, the upregulation of angiopoietin-1 expression may exert potential impacts. To the best of our knowledge, this is the first report on the changes in renal interstitial pericytes in aging human kidneys.

Salvage treatment of forearm arteriovenous fistula with small caliber inflow distal artery by percutaneous transluminal angioplasty.

BACKGROUND: Dysfunctional distal arteriovenous fistulas (AVFs) with small caliber distal inflow arteries theoretically require percutaneous transluminal angioplasty (PTA) throughout the entire arterial length. However, in clinical practice, whole distal inflow arterial PTA is not frequently performed due to concerns about possible arterial rupture. Therefore, we investigated the safety and efficacy of this procedure at our center, comparing it with the standard venous PTA. METHODS: From March 2017 to December 2022, 48 cases of distal AVF salvaged by whole distal inflow arterial PTA were assigned into a treatment group and 121 cases of distal AVF salvaged by venous standard PTA not involving the whole inflow artery were assigned into a control group. These two groups were then compared. RESULTS: Those in the treatment group (who received whole distal inflow arterial PTA) were older than those in the control group (mean age, 69 vs 59 years, p < 0.001). Otherwise, differences between the two groups were unremarkable. After the salvage treatment, primary patency seemed to decrease in the treatment group with whole distal inflow arterial PTA compared to the control group with conventional PTA, although such decrease was not significant (p = 0.072). However, primary assisted patency and secondary patency were comparable between the two groups (p = 0.350 and p = 0.590, respectively). And in the treatment group, only one arterial dissection occurred, which was successfully managed with balloon tamponade so that no distal AVF was abandoned due to complications following whole distal inflow arterial PTA. CONCLUSION: Whole distal inflow arterial PTA is an effective and safe option for distal AVF salvage with a narrowed inflow artery, frequently refractory to conventional venous PTA.

Clinical significance of neutrophil-to-lymphocyte ratio on the risk of abdominal aortic calcification and decreased bone mineral density in patients with end-stage kidney disease.

Inflammation plays a major role in the pathogenesis of chronic kidney disease (CKD), but the relationship between systemic inflammation and CKD-mineral bone disease is unclear. We aimed to investigate whether the neutrophil-to-lymphocyte ratio (NLR) is related to abdominal aortic calcification (AAC) and bone mineral density (BMD) in dialysis patients. In this cross-sectional analysis using baseline data of a multicenter cohort, a total of 759 patients were divided into three groups according to NLR level, and the associations between NLR and Kauppila AAC score (AACS) and BMD were assessed. The highest tertile NLR group had more males, alcohol consumers, higher diabetes prevalence, and higher comorbidity index than the lowest tertile NLR group. Fasting glucose and C-reactive protein levels were higher, while serum albumin, serum iron, and lipid profiles except triglycerides were lower in the highest tertile group. AACS was significantly higher in the highest tertile group than in the lowest and middle tertile groups (p = 0.017), but the mean areal BMD and T-score of the lumbar spine and femur were not different between groups. NLR level was positively correlated with AACS in all aortic wall segments except L1 and L3 anterior. In multivariable logistic regression analysis, the highest tertile NLR group was independently associated with AAC (odds ratio 2.876, 95% confidence interval 1.250-6.619, p = 0.013) but was not associated with osteoporosis in the lumbar spine and femur after adjusting for confounding factors. The NLR can be used as a potential indicator of AAC in dialysis patients.

Safety and durable patency of tunneled hemodialysis catheter inserted without fluoroscopy.

BACKGROUND: A tunneled hemodialysis (HD) catheter is preferred due to its lower incidence of infection and malfunction than non-tunneled ones. For safer insertion, fluoroscopic guidance is desirable. However, if the patient is unstable, transfer to the fluoroscopy may be impossible or inappropriate. METHODS: From June 2019 to September 2022, 81 tunneled HD catheter insertion cases performed under ultrasound guidance without fluoroscopy and 474 cases with fluoroscopy in our institutional HD catheter cohort were retrospectively compared. RESULTS: Immediate complications, later catheter-associated problems, including infections and catheter dysfunction, were comparable between the two groups (p = 0.20 and p = 0.37, respectively). The patency of tunneled catheters inserted without fluoroscopy was comparable to the patency of tunneled catheters inserted with fluoroscopic guidance (p = 0.90). CONCLUSION: Tunneled HD catheter insertion without fluoroscopy can be performed safely and has durable patency compared to the insertion with fluoroscopy. Therefore, this method can be considered for the selected unstable patients (e.g., ventilator care) in the intensive care unit.

Comparison of the performance of currently used estimated glomerular filtration rate equations with 24-hour urine creatinine clearance: sample analysis of randomised controlled trial participants.

OBJECTIVE: There are several equations for estimating the glomerular filtration rate (GFR), and each method has its limitations. We compared various estimated GFR (eGFR) equations with 24 hours urine creatinine clearance (24u-CCr). DESIGN: Sample analysis of randomised controlled trial participants. SETTING AND PARTICIPANTS: We compared the mean 24u-CCr values measured 2-3 times for 211 patients with eGFR values calculated using the following equations: isotope dilution mass spectrometry-Modification of Diet in Renal Disease (IDMS-MDRD) equation, Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation, equations for Koreans (KOR-IDMS-MDRD and KOR-CKD-EPI) and full age spectrum equation. OUTCOME MEASURES: Performance of various creatinine-based eGFR equations, including those with Korean coefficients, compared with the results of the 24u-CCr. RESULTS: IDMS-MDRD showed the best overall correlation with the 24u-CCr (R=0.949, p<0.001), and KOR-CKD-EPI showed the best agreement in terms of the intraclass correlation coefficient (ICC, 0.969, 95% CI 0.959 to 0.976, p<0.001). In subgroup analysis, IDMS-MDRD-GFR showed the highest ICCs in CKD stages 1 and 3 (ICC 0.872 in stage 1 and 0.927 in CKD stage 3, all p<0.001). KOR-CKD-EPI showed the highest ICC in CKD stage 2 (ICC 0.854, p<0.001). Overall, the accuracy of CKD-EPI (2021) was the highest at P15 (15%) and P30 (30%) (P15: 65.4 and P30: 97.6). In addition, CKD-EPI (2021) showed the highest P30 accuracy in CKD stage 1 (98.7), whereas KOR-IDMS-MDRD showed the highest P30 accuracy in CKD stages 2 and 3 (98.8 and 98.2, respectively). CONCLUSIONS: The IDMS-MDRD equation showed the best correlation and overall good agreement with the 24u-CCr; however, the accuracy was low. The most accurate measurements were obtained using the CKD-EPI (2021) equation in CKD stage 1 and the KOR-IDMS-MDRD equation in CKD stages 2-3; nevertheless, the CKD-EPI (2021) equation showed the best overall accuracy. TRIAL REGISTRATION NUMBER: NCT01552954.

Korean guidelines for the management of gout.

Gout is the most common form of arthritis, with the prevalence increasing worldwide. The present treatment guidelines provide recommendations for the appropriate treatment of acute gout, management during the inter-critical period, and prevention of chronic complications. The guidelines were developed based on evidence-based medicine and draft recommendations finalized after expert consensus. These guidelines are designed to provide clinicians with clinical evidence to enable efficient treatment of gout.

Korean guidelines for the management of gout.

Gout is the most common form of arthritis, with the prevalence increasing worldwide. The present treatment guidelines provide recommendations for the appropriate treatment of acute gout, management during the inter-critical period, and prevention of chronic complications. The guidelines were developed based on evidence-based medicine and draft recommendations finalized after expert consensus. These guidelines are designed to provide clinicians with clinical evidence to enable efficient treatment of gout.

Comparison of dominant and nondominant C3 deposition in primary glomerulonephritis.

BACKGROUND: Alternative complement pathway dysregulation plays a key role in glomerulonephritis (GN) and is associated with C3 deposition. Herein, we examined pathological and clinical differences between cases of primary GN with C3-dominant (C3D-GN) and nondominant (C3ND-GN) deposition. METHODS: We extracted primary GN data from the Korean GlomeruloNEphritis sTudy (KoGNET). C3D-GN was defined as C3 staining two grades greater than C1q, C4, and immunoglobulin via immunofluorescence analysis. To overcome a large difference in the number of patients between the C3D-GN and C3ND-GN groups (31 vs. 9,689), permutation testing was used for analysis. RESULTS: The C3D-GN group exhibited higher serum creatinine (p ≤ 0.001), a greater prevalence of estimated glomerular filtration rate of <60 mL/min/1.72 m2 (p ≤ 0.001), higher (but not significantly so) C-reactive protein level, and lower serum C3 level (p ≤ 0.001). Serum albumin, urine protein/creatinine ratio, number of patients who progressed to end-stage renal disease, and all-cause mortality were comparable between groups. Interstitial fibrosis and mesangial cellularity were greater in the C3D-GN group (p = 0.04 and p = 0.01, respectively) than in the C3ND-GN group. C3 deposition was dominant in the former group (p < 0.001), in parallel with increased subendothelial deposition (p ≤ 0.001). CONCLUSION: Greater progression of renal injury and higher mortality occurred in patients with C3D-GN than with C3ND-GN, along with pathologic differences in interstitial and mesangial changes.

Prognostic value of chronicity grading on renal outcomes in patients with IgA nephropathy.

Many studies have shown that chronic changes are strong predictors of renal outcomes in various kidney diseases, including IgA nephropathy. The Mayo Clinic/Renal Pathology Society suggested a glomerulonephritis reporting system with a proposal for standardized grading of chronic changes. The purpose of this study was to predict renal outcomes in patients with IgA nephropathy using chronicity grading in comparison to the Oxford classification which did not include global sclerosis. A total of 4,151 patients with IgA nephropathy were enrolled from the Korean GlomeruloNephritis Study Group registry. Chronicity grading was categorized into minimal, mild, moderate, and severe according to the extent of chronic changes. The Oxford T and S scores were considered as chronic lesions. Three prediction models were constructed: the Oxford classification model (Oxford S plus T), chronicity grading model A (chronicity grading), and chronicity grading model B (chronicity grading plus Oxford S). Using these three prediction models, the primary renal outcome (end-stage renal disease) was evaluated using Cox regression analysis and prediction performance. During the median follow-up of 6.1 (2.7-9.9) years, 304 (7.3%) patients progressed to end-stage renal disease with a cumulative incidence rate of 1.02 events per 100 person-years. In a fully adjusted multivariable model, chronicity grading was independently associated with the primary renal outcome in both models A and B. Compared to the Oxford model, both models A and B showed improvements in model fit, but not in discrimination (ΔC 0.001; 95% CI, -0.010 to 0.013 and ΔC 0.002; 95% CI, -0.005 to 0.008, respectively). Model B demonstrated improvements in integrated discrimination improvement (0.01; 95% CI, 0-0.03) and continuous net reclassification improvement (0.49; 95% CI, 0.02-0.72). The severity of chronicity grading is closely related to adverse renal outcomes in patients with IgA nephropathy, and chronicity grading could provide additional information in clinical practice alongside the Oxford classification.

A multicenter, randomized, open-label, comparative, phase IV study to evaluate the efficacy and safety of combined treatment with mycophenolate mofetil and corticosteroids in advanced immunoglobulin A nephropathy.

BACKGROUND: It remains unclear whether immunosuppressive agents are effective in patients with immunoglobulin A nephropathy (IgAN). We investigated the efficacy of a mycophenolate mofetil (MMF) and corticosteroid combination therapy in patients with advanced IgAN. METHODS: We conducted a multicenter, randomized, placebo-controlled, parallel-group study of 48 weeks administration of MMF and corticosteroids in biopsy-proven advanced IgAN patients with estimated glomerular filtration rate (eGFR) of 20-50 mL/min/1.73 m2 and urine protein-to-creatinine ratio (UPCR) of >0.75 g/day. The primary outcome was complete (UPCR < 0.3 g/day) or partial (>50% reduction of UPCR compared to baseline) remission at 48 weeks. RESULTS: Among the 48 randomized patients, the percentage that achieved complete or partial remission was greater in the combination therapy group than in the control group (4.2% vs. 0% and 29.1% vs. 5.0%, respectively). Compared with the combination therapy group, eGFR in the control group decreased significantly from week 36 onward, resulting in a final adjusted mean change of -4.39 ± 1.22 mL/min/1.73 m2 (p = 0.002). The adjusted mean changes after 48 weeks were 0.62 ± 1.30 and -5.11 ± 1.30 mL/min/1.73 m2 (p = 0.005) in the treatment and control groups, respectively. The UPCR was significantly different between the two groups; the adjusted mean difference was -0.47 ± 0.17 mg/mgCr and 0.07 ± 0.17 mg/mgCr in the treatment and control group, respectively (p = 0.04). Overall adverse events did not differ between the groups. CONCLUSION: In advanced IgAN patients with a high risk for disease progression, combined MMF and corticosteroid therapy appears to be beneficial in reducing proteinuria and preserving renal function.

Pressure-Natriuresis Response Is Diminished in Old Age.

BACKGROUND: Age-related alterations in renal sodium handling affect blood pressure (BP). We aimed to clarify whether the pressure-natriuresis response changes with age, leading to BP elevation. METHODS: A total of 4,859 participants with normal renal function from the Korean Genome and Epidemiology Study (KoGES) and 235 patients with non-diabetic chronic kidney disease (CKD) from the ESPECIAL trial were included and divided into the younger and older groups. In ESPECIAL, participants took olmesartan from weeks 0 to 16 and were educated about a low-salt diet (LSD) from weeks 8 to 16. RESULTS: In both studies, older participants showed lower estimated glomerular filtration rate (eGFR) and urine concentration index and higher albuminuria. In KoGES, BP was higher and urine sodium was lower in older participants. In ESPECIAL, diastolic BP at 0 week was lower in older participants. Olmesartan reduced BP in both groups, whereas LSD decreased systolic BP only in older participants. Urine sodium increased in younger participants but decreased in older participants after olmesartan use. In KoGES, urine sodium was correlated with BP in both groups after adjusting for age, sex, and eGFR; however, the correlation coefficient was lower in older participants. In ESPECIAL, only younger participants showed a significant positive association between systolic BP and urine sodium in multiple regression analysis. CONCLUSIONS: The pressure-natriuresis response was diminished in older participants with or without CKD.

Adiponectin receptor agonist ameliorates cardiac lipotoxicity via enhancing ceramide metabolism in type 2 diabetic mice.

Accumulation of lipids and their metabolites induces lipotoxicity in diabetic cardiomyopathy. Lowering ceramide concentration could reduce the impact of metabolic damage to target organs. Adiponectin improves lipotoxicity through its receptors (AdiopRs), which have sequence homology with ceramidase enzymes. Therefore, cardioprotective role of AdipoR agonism by AdipoRon was investigated. Sixteen-week-old male db/m and db/db mice were fed a diet containing AdipoRon for four weeks. Phenotypic and metabolic profiles with associated cellular signaling pathways involved in lipid metabolism were investigated in the mice heart and human cardiomyocytes to establish treatment effect of AdipoRon. AdipoRon ameliorated insulin resistance, fibrosis, M1-dominant inflammation, and apoptosis in association with reduced accumulations of free fatty acid, triglycerides, and TLR4-related ceramide in the heart. This resulted in overall reduction in the level of oxidative stress which ameliorated cardiac hypertrophy and its function. AdipoRon increased the expression of AdipoR1 and AdipoR2 via pAMPK/FoxO1-induced Akt phosphorylation resulting from a decrease in PP2A level. It also increased acid ceramidase activity which reduced ceramide and increased sphingosine-1 phosphate levels in the heart of db/db mice and cultured human cardiomyocytes. Consistent upregulation of AdipoRs and their downstream regulatory pathways involving pAMPK/PPARα/PGC-1α levels led to lipid metabolism enhancement, thereby improving lipotoxicity-induced peroxisome biogenesis and oxidative stress. AdipoRon might control oxidative stress, inflammation, and apoptosis in the heart through increased AdipoR expression, acid ceramidase activity, and activation of AMPK-PPARα/PGC-1α and related downstream pathways, collectively improving cardiac lipid metabolism, hypertrophy, and functional parameters.

Relationships between monocyte count to high-density lipoprotein cholesterol ratio and cardiovascular outcomes in patients commencing dialysis.

OBJECTIVE: High monocyte to high-density lipoprotein cholesterol ratio (MHR) is known to be a risk factor for cardiovascular (CV) complications. We aimed to evaluate the relationship between MHR and CV outcomes in patients commencing dialysis. METHODS: The medical records of patients who started maintenance dialysis between January 2006 and July 2017 were reviewed. The primary outcomes were all-cause mortality and overall CV mortality and the secondary outcomes were CV event-free survival and the incidence of CV complications. RESULTS: Five hundred ninety-seven patients were enrolled and allocated to low- or high-MHR groups. All-cause mortality did not differ between the groups during a mean follow-up period of 3.9 years. In addition, overall CV mortality did not differ between the groups. However, CV event-free survival was significantly lower in the high-MHR group than in the low-MHR group (47.5% vs. 59.0%). Multivariate Cox regression analysis showed that high MHR was an independent predictor of CV events (HR 1.886, 95% CI 1.015-3.505). CONCLUSION: High MHR at the time of initiation of dialysis may represent a useful predictor of CV complications.

Effects of periostin deficiency on kidney aging and lipid metabolism.

Periostin plays a crucial role in fibrosis, which is involved in kidney aging. A few studies have shown that lipid metabolism is involved in kidney aging. We investigated the role of periostin in lipid metabolism during kidney aging. Renal function, fibrosis, and inflammatory markers were studied using urine, blood, and tissue samples from wild-type (WT) C57BL/6 mice and Postn-null mice of 2 and 24 months of age. Lipids were quantitatively profiled using liquid chromatography-tandem mass spectrometry in the multiple reaction monitoring mode. Renal function was worse and tubular atrophy/interstitial fibrosis, periostin expression, and inflammatory and fibrotic markers were more severe in aged WT mice than in young WT mice. In aged Postn-null mice, these changes were mitigated. Thirty-five differentially regulated lipids were identified. Phosphatidylcholines, cholesteryl ester, cholesterol, ceramide-1-phosphate, and CCL5 expression were significantly higher in aged WT mice than in aged Postn-null mice. Particularly, linoleic acid, linolenic acid, arachidonic acid, and docosahexaenoic acid differed strongly between the two groups. Lysophosphatidylcholine acyltransferase 2, which converts lysophosphatidylcholine to phosphatidylcholine, was significantly higher in aged WT mice than in aged Postn-null mice. Periostin expression in the kidneys increased with age, and periostin ablation delayed aging. Changes in lipids and their metabolism were found in Postn-null mice. Further research on the precise mechanisms of and relationships between lipid expression and metabolism, kidney aging, and periostin expression is warranted.

Nicotine exacerbates tacrolimus-induced renal injury by programmed cell death.

BACKGROUND/AIMS: Cigarette smoking is an important modifiable risk factor in kidney disease progression. However, the underlying mechanisms for this are lacking. This study aimed to assess whether nicotine (NIC), a major toxic component of cigarette smoking, would exacerbates tacrolimus (TAC)-induced renal injury. METHODS: Sprague-Dawley rats were treated daily with NIC, TAC, or both drugs for 4 weeks. The influence of NIC on TAC-caused renal injury was examined via renal function, histopathology, oxidative stress, mitochondria, endoplasmic reticulum (ER) stress, and programmed cell death (apoptosis and autophagy). RESULTS: Both NIC and TAC significantly impaired renal function and histopathology, while combined NIC and TAC treatment aggravated these parameters beyond the effects of either alone. Increased oxidative stress, ER stress, mitochondrial dysfunction, proinf lammatory and profibrotic cytokine expressions, and programmed cell death from either NIC or TAC were also aggravated by the two combined. CONCLUSION: Our observations suggest that NIC exacerbates chronic TAC nephrotoxicity, implying that smoking cessation may be beneficial for transplant smokers taking TAC.

Role of Aberrantly Activated Lysophosphatidic Acid Receptor 1 Signaling Mediated Inflammation in Renal Aging.

The increasing load of senescent cells is a source of aging, and chronic inflammation plays a pivotal role in cellular senescence. In addition, senescent renal tubular epithelial cells are closely associated with renal aging. Lysophosphatidic acid (LPA) is a bioactive lipid mainly produced by the catalytic action of autotaxin (ATX), and its ligation to LPA receptor-1 (LPAR1) is associated with chronic inflammation and renal fibrosis; however, its role in renal aging is unclear. Male 2-, 12-, and 24-month-old C57BL/6 mice and Human renal proximal tubular epithelial cells (HRPTEpiC) were used in the present study. DNA damage and oxidative stress-induced senescence were simulated using doxorubicin (DOXO) and H2O2, respectively. The aged kidney showed decreased renal function, increased fractional mesangial area, and tubulointerstitial fibrosis. Both aged kidney and senescent cells showed increased levels of LPAR1, Nuclear factor κB (NF-κB), and inflammatory cytokines. In addition, LPAR1-knockdown reduced NF-κB and subsequent inflammatory cytokine induction, and NF-κB-knockdown resulted in decreased LPAR1 expression. Our study revealed a positive feedback loop between LPAR1 and NF-κB, which reinforces the role of inflammatory response, suggesting that blocking of aberrantly activated LPAR1 may reduce excessive inflammation, thereby providing a new possible therapeutic strategy to attenuate renal aging.

Renal Outcome of IgM Nephropathy: A Comparative Prospective Cohort Study.

Immunoglobulin M nephropathy (IgMN) is an idiopathic glomerulonephritis characterized by diffuse deposits of IgM in the glomerular mesangium. However, its renal prognosis remains unknown. We compared renal outcomes of IgMN patients with those of patients with minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), or mesangial proliferative glomerulonephritis (MsPGN) from a prospective observational cohort, with 1791 patients undergoing native kidney biopsy in eight hospitals affiliated with The Catholic University of Korea between December 2014 and October 2020. IgMN had more mesangial proliferation and matrix expansion than MsPGN and more tubular atrophy and interstitial fibrosis than MCD. IgMN patients had decreased eGFR than MCD patients in the earlier follow-up. However, there was no significant difference in urine protein or eGFR among all patients at the last follow-up. When IgMN was divided into three subtypes, patients with FSGS-like IgMN tended to have lower eGFR than those with MCD-like or MsPGN-like IgMN but higher proteinuria than MsPGN-like IgMN without showing a significant difference. The presence of hypertension at the time of kidney biopsy predicted ≥20% decline of eGFR over two years in IgMN patients. Our data indicate that IgMN would have a clinical course and renal prognosis similar to MCD, FSGS, and MsPGN.

Cardiovascular Risk Comparison between Expanded Hemodialysis Using Theranova and Online Hemodiafiltration (CARTOON): A Multicenter Randomized Controlled Trial.

Expanded hemodialysis (HDx) with medium cutoff (MCO) membranes, which remove middle-to-large molecules well, may be a good option to replace online hemodiafiltration (online-HDF). To provide more evidence, this randomized controlled trial compared several cardiovascular parameters between patients undergoing HDx and online-HDF. Eighty patients undergoing thrice-weekly hemodialysis were randomly assigned to receive either HDx with a Theranova membrane (n = 43) or online-HDF (n = 37). The primary endpoints were changes in brachial-ankle pulse wave velocity (baPWV), echocardiographic parameters, and coronary artery calcium (CAC) scores over 1 year, and the secondary endpoints included blood cardiovascular biomarkers, mortality, and patient-reported outcomes. A linear mixed model and log-rank test were used to estimate the group differences. 65 patients had completed the trial. The changes in baPWV and echocardiographic parameters did not differ between the two groups. The CAC scores remained stable in the online-HDF group, whereas an increasing trend was shown in the HDx group (P = 0.012). Other endpoints, including cardiovascular and all-cause mortalities, were similar between the two groups. The changes in cardiovascular parameters did not differ between HDx with an MCO membrane and online-HDF. However, attention may be needed in patients with high CAC scores or scores with an increasing tendency when online-HDF is replaced with HDx with an MCO membrane.