Abstract Although various strategies for steroid withdrawal after transplantation have been attempted, there are few reports of the long‐term results of steroid withdrawal regimens in kidney transplantation. Earlier, we reported on a 5‐year prospective, randomized, single‐center trial comparing the safety and efficacy of cyclosporine (CsA) plus mycophenolate mofetil ( MMF ) with that of tacrolimus ( TAC ) plus MMF , when steroids were withdrawn 6 months after kidney transplantation in low‐risk patients. We now report the 10‐year observational data on the study population. We collected data from the database of the Organ Transplantation Center, Samsung Medical Center for 5 years after completion of the original study ( TAC group n = 62; CsA group n = 55). The 10‐year patient survival, death‐censored graft survival, and acute rejection‐free survival did not differ between groups (98% vs 96%; P = 0.49, 78% vs 85%; P = 0.75 and 84% vs 76%; P = 0.14 in the TAC group vs CsA group, respectively). In low‐risk patients, there was no difference in long‐term patient and graft survival between TAC ‐ and CsA‐based late steroid withdrawal regimens that included MMF treatment. More long‐term randomized clinical trials are needed to clarify the benefits of late steroid withdrawal in kidney transplantation.
It remains uncertain whether albuminuria can identify elderly patients with diabetes at a high risk of incident end-stage kidney disease (ESKD) or mortality. 3065 patients (aged ≥ 65 years) with type 2 diabetes were included. We examined the association between albuminuria stages (normoalbuminuria, A1; microalbuminuria, A2; and macroalbuminuria, A3) and the risk of incident ESKD and all-cause mortality for each age group (65-69, 70-74, and ≥ 75 years). A2 and A3 were observed in 25.5% and 9.4% of the subjects, respectively. For A1, A2, and A3, the probabilities of ESKD at 8 years were 1.0%, 6.3%, and 29.7% (P < 0.001 for all), and the all-cause mortality was 13.1%, 27.4%, and 31.7% (P < 0.001 for A1 vs A2, P < 0.001 for A1 vs A3), respectively. Albuminuria stages were independently associated with an increased risk of ESKD [fully adjusted hazard ratios (HR): 3.650 (1.987-6.702) for A2, 10.404 (5.706-18.972) for A3 vs. A1]. The HRs of all-cause mortality were 1.742 (1.411-2.153) for A2 and 1.810 (1.344-2.441) for A3. The associations between albuminuria stages and the risk of ESKD and all-cause mortality were consistent across all age groups. Even microalbuminuria is also a risk factor for incident ESKD and mortality in elderly patients with diabetes.
Abstract It remains uncertain whether albuminuria can identify elderly patients with diabetes at a high risk of incident end-stage kidney disease (ESKD) or mortality. 3,065 patients (aged ≥65 years) with type 2 diabetes were included. We examined the association between albuminuria stages (normoalbuminuria, A1; microalbuminuria, A2; and macroalbuminuria, A3) and the risk of incident ESKD and all-cause mortality for each age group (65–69, 70–74, and ≥75 years). A2 and A3 were observed in 25.5% and 9.4% of the subjects, respectively. For A1, A2, and A3, the probabilities of ESKD at 8 years were 1.0%, 6.3%, and 29.7% ( P <0.001 for all), and the all-cause mortality was 13.1%, 27.4%, and 31.7% ( P <0.001 for A1 vs A2, P <0.001 for A1 vs A3), respectively. Albuminuria stages were independently associated with an increased risk of ESKD [fully adjusted hazard ratios (HR): 3.650 (1.987–6.702) for A2, 10.404 (5.706–18.972) for A3 vs. A1]. The HRs of all-cause mortality were 1.742 (1.411–2.153) for A2 and 1.810 (1.344–2.441) for A3. The associations between albuminuria stages and the risk of ESKD and all-cause mortality were consistent across all age groups. Microalbuminuria is also a risk factor for incident ESKD and mortality in elderly patients with diabetes.
INTRODUCTION AND AIMS: Glomerular disease involves morphological changes in podocyte cells resulting in defective filtration and proteinuria accompanied by inflammation and fibrosis.Changes in podocyte motility are associated with foot process effacement and proteinuria.The actin cytoskeleton plays an important role maintaining the podocyte foot process.Cardiotrophin-1 (CT-1), a member of the interleukin-6 family of cytokines, induces hypertrophy in cardiomyocytes and binds to receptors glycoprotein 130 (gp130) and leukemia inhibitory factor receptor (LIFR).CT-1 has a protective effect in several organs, promoting survival and exerting antiapoptotic and anti-inflammatory effects.Moreover, CT-1 regulates migration in cardiomyofibroblasts and endothelial cells.However, little is known about the role of CT-1 on glomerular injury and in the biology of podocytes.Thus, we analyzed CT-1 glomerular expression in a mouse model of nephrotoxic serum-induced glomerulonephritis (NTS) and we assessed whether modulating CT-1 levels has any effect on podocyte migration, proliferation and actin cytoskeleton.METHODS: Glomerular disease was induced by nephrotoxic serum (NTS) injection.Kidneys were collected from mice 7 (n=7) or 21 days (n=6) after NTS administration and from control mice without disease (n=5).Differentiated immortalized mouse podocytes were cultured and transfected with 10nM siRNA against CT-1 or stimulated with 40 ng/ml CT-1 to assess changes on migration, proliferation, the actin cytoskeleton, and RhoA and Cdc42 activation.RESULTS: The protein level of CT-1 around the glomerulus was reduced in diseased kidneys after 7 or 21 days of NTS administration compared with healthy kidneys.CT-1 and its receptors (LIFR and GP130) were localized in podocytes, both in vivo and in vitro (in primary culture of mouse podocytes and in immortalized mouse podocytes) and podocyte CT-1 expression was not changed in disease.Although knock-down of endogenous CT-1 in immortalized mouse podocytes did not influence cell viability, it increased migration, reduced Cdc42 activity, reduced the percentage of cells with stress actin fiber organization, and reduced area and mean fluorescence observed by phalloidin immunofluorescence.Exogenous administration of CT-1 in these cells did not modify viability and motility but reduced RhoA activity, increased the percentage of cells with stress actin fiber organization and the area and mean fluorescence observed by phalloidin inmunofluorescence CONCLUSIONS: This study shows that CT-1 levels are altered in glomerulonephritis and that CT-1 can modulate podocyte shape and function, thus suggesting a therapeutic application of this molecule in the progression of the glomerular damage.
Arteriovenous graft for hemodialysis shows poorer outcomes than arteriovenous fistula, due to frequent stenosis and thrombosis. We investigated arteriovenous graft patency outcomes and prognostic factors for these outcomes.We included a single-center cohort of patients receiving arteriovenous graft for hemodialysis access from 2010 to 2014. Demographics, laboratory data, comorbidities, and medications were collected from medical records. Surgical factors related to graft operation including the type and diameter of connected vessels, graft location, and type of operation (elective or emergency) were also recorded. Outcomes included primary and secondary patency. Survival analysis was conducted using the Kaplan-Meier method; univariate and multivariate analyses were used to evaluate the prognostic factors.Data from 225 grafts were analyzed. During the follow-up period (mean: 583 days, range: 1-1717 days), 138 (61%) grafts required intervention and 46 (20%) permanently failed. Primary patency at one, two, and three years was 42%, 20%, and 16%, respectively. Secondary patency at one, two, and three years was 85%, 72%, and 64%, respectively. Multivariate analysis showed that primary patency was negatively associated with increasing age and location of vessel anastomosis (reference-brachiobrachial anastomosis; brachiobasilic - HR, 0.569; 95% CI, 0.376-0.860; p = 0.007; brachioaxillary anastomosis - HR 0.407; 95% CI, 0.263-0.631; p < 0.0001); secondary patency was positively associated with diastolic blood pressure, serum albumin level, and hemoglobin over 10 g/dL. Adverse events other than stenosis or thrombosis, such as infection/inflammation or pseudoaneurysm were observed in approximately 20% of grafts.Factors associated with diminished primary arteriovenous graft patency included increased patient age and location of vessel anastomosis (brachiobrachial type compared to brachiobasilic or brachioaxillary type); diminished secondary patency was associated with low diastolic blood pressure, low serum albumin, and hemoglobin level under 10 g/dL. Among these factors, diastolic blood pressure, serum albumin, and hemoglobin level may be modifiable and could improve arteriovenous graft patency outcomes.
Abstract Background IgA nephropathy (Ig AN ) is the most frequent primary glomerular disease and the leading cause of end‐stage renal disease. We investigated clinicopathologic predictors of renal survival in patients with Ig AN with a focus on glomerular filtration rate ( GFR ) decline slope. Materials and methods We screened all patients with primary Ig AN between 1995 and 2012. Renal progression was defined as doubling of serum creatinine. Using serial serum creatinine levels during the first‐year, we calculated the GFR decline slopes. Further, we defined patients in the steepest GFR slope quartile as rapid decliners and those in the second steepest GFR slope quartile as slow decliners. Others were defined as nondecliners. Results Of 214 participants, baseline GFR was 81 (62, 100) mL/min/1.73 m 2 , which was not different among the 3 groups. Rapid decliners and slow decliners had higher levels of urinary protein/creatinine ratio (0.88, 0.89 and 0.58 g/ gC r, respectively, P < .001). Five‐year renal survival was 76% in rapid decliners, 91% in slow decliners and 100% in nondecliners ( P < .001, rapid or slow decliners vs nondecliners). After adjustment for clinicopathologic variables, slow decliners were associated with an 8.8‐fold higher risk of progression ( P = .011), and rapid decliners were associated with a 10.2‐fold increased risk of progression ( P = .007) compared with nondecliners. Conclusions First‐year GFR slope was associated with increased risk of renal progression, independent of proteinuria and histologic findings. Further studies are needed to investigate whether early GFR change can identify high‐risk patients who benefit from immunosuppressive treatment in Ig AN .
Abstract Crescentic glomerulonephritis (CrGN) usually requires urgent immunosuppressive treatment. However, aggressive immunosuppressive treatment is often difficult because of the patients’ medical conditions or comorbidities. Prognostic markers including urinary cytokines/chemokines as noninvasive biomarkers were explored in CrGN patients. This prospective cohort study included 82 patients with biopsy-confirmed CrGN from 2002 to 2015 who were followed up for 5 years. Urine and serum cytokines/chemokines on the day of kidney biopsy were analyzed in 36 patients. The median age was 65 years and 47.6% were male. Baseline estimated glomerular filtration rate (eGFR) and interstitial fibrosis and tubular atrophy (IFTA) scores were identified as significant prognostic factors. Among patients with cytokines/chemokines measurement, increased IL-10 level was identified as an independent predictor of good prognosis, and increased levels of urinary MCP-1 and fractalkine tended to be associated with good prognosis after adjusting for baseline eGFR and IFTA score. However, semiquantitative analysis of intrarenal leukocytes did not show prognostic value predicting renal outcome or correlation with urinary cytokines/chemokines. This study supports the clinical importance of baseline eGFR and IFTA scores and suggests potential usefulness of urinary IL-10, MCP-1, and fractalkine as prognostic markers for predicting renal outcomes in patients with CrGN.
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