Using the Oxford classification of IgA nephropathy to predict long-term outcomes of Henoch-Schönlein purpura nephritis in adults.

Recently, there has been emerging concern that crescents, the main histologic feature of Henoch-Schönlein purpura nephritis, merely reflect active inflammation, and may not be useful in predicting long-term outcomes. We therefore conducted a single-center retrospective study to evaluate whether the new Oxford classification of immunoglobulin A nephropathy can be used to predict long-term outcome in patients with Henoch-Schönlein purpura nephritis. We included 61 biopsy-proven patients with Henoch-Schönlein purpura nephritis between January 1991 and August 2010. In addition to the International Study of Kidney Disease in Children classification, pathologic findings were also evaluated by the Oxford classification. Primary outcomes were defined as either the onset of estimated glomerular filtration rate <60 ml/min per 1.73 m(2) with ≥30% decrease in estimated glomerular filtration rate from baseline or end-stage renal disease. During a median follow-up of 49.3 months, 13 (21%) patients reached the primary end point. A Kaplan-Meier plot showed that renal event-free survival was significantly longer in patients with <50% crescents than in those with crescents in ≥50% of glomeruli (P=0.003). Among the components of the Oxford classification, patients with endocapillary hypercellularity (E1; P=0.016) and tubular atrophy/interstitial fibrosis (T1/T2; P=0.018) had lower renal survival rates than those with E0 and T0. In a multivariate Cox model adjusted for clinical and pathologic factors, E1 (hazard ratio=8.91; 95% confidence interval=1.47-53.88; P=0.017) and T1/T2 (hazard ratio=8.74; 95% confidence interval=1.40-54.38; P=0.020) were independently associated with reaching a primary outcome, whereas the extent of crescentic lesions was not. Our findings suggest that the Oxford classification can be used in predicting long-term outcomes of Henoch-Schönlein purpura nephritis.

Increased dialysate MCP-1 is associated with cardiovascular mortality in peritoneal dialysis patients: a prospective observational study.

BACKGROUND: The aim of this study was to investigate the association between the dialysate MCP-1 (dMCP-1) and systemic inflammatory and nutritional markers in peritoneal dialysis (PD) patients. In addition, we examined the prognostic value of dMCP-1 on all-cause or cardiovascular mortality in these patients. METHODS: We prospectively followed 169 prevalent PD patients from April 1st 2008 to December 31st 2012. At baseline, dMCP-1 and serum biochemical parameters including high sensitivity CRP (hs-CRP) and albumin were checked. All-cause mortality and cause of death were evaluated during the follow-up period. Based on the median level of dMCP-1, patients were classified as either low or high dMCP-1 groups. RESULTS: Mean age, hs-CRP, and D/Pcr ratio at 4 h were significantly higher, while serum albumin levels and %lean body mass (LBM) were significantly lower in the high dMCP-1 group. During the mean follow-up period of 47.7 months, all-cause mortality and cardiovascular mortality rate were significantly higher in the high dMCP-1 group (9.6 and 6.3 per 100 person-years, respectively) compared to the low dMCP-1 group (5.1 and 3.1 per 100 person-years, respectively; p = 0.021, 0.038). In multivariate Cox analysis, high dMCP-1 was a significant independent predictor of all-cause mortality (hazard ratio: 1.83, 95% confidence interval: 1.03-3.24, p = 0.039). CONCLUSIONS: dMCP-1 levels are closely correlated with nutritional and systemic inflammatory markers in PD patients. In addition, increased dMCP-1 is significantly associated with higher all-cause and cardiovascular mortality. These findings suggest that local peritoneal inflammation could contribute to poor clinical outcomes in PD patients.

Interdialytic weight gain and cardiovascular outcome in incident hemodialysis patients.

BACKGROUND: Interdialytic weight gain (IDWG) has been regarded as a surrogate of volume overload, but also as a marker of a better nutritional status in end-stage renal disease (ESRD) patients on hemodialysis (HD). This paradoxical meaning of IDWG requires further investigation, particularly in adverse cardiovascular outcomes. METHODS: A prospective cohort of 1,013 incident HD patients from 36 HD centers of the Clinical Research Center for ESRD in Korea was included. Patients were categorized into five groups according to the IDWG%, a ratio of absolute IDWG to dry weight: <1.0, ≥4.0, and every 1.0 increment in between. Primary outcome was major adverse cardiac and cerebrovascular events (MACCE). RESULTS: During a mean follow-up of 18.7 months, primary outcome was observed in 104 patients (10.3%). In multivariate analysis, compared to patients with IDWG% of 1.0-1.9 (reference group), the hazard ratios (HRs) for primary outcome in the IDWG% <1.0, 2.0-2.9, 3.0-3.9, and ≥4.0 groups were 1.10 [95% confidence interval (CI) 0.55-2.20, p = 0.80], 1.15 (95% CI 0.59-2.27, p = 0.68), 1.80 (95% CI 0.95-3.41, p = 0.07), and 1.93 (95% CI 1.02-3.64, p = 0.04), respectively. Furthermore, even when residual renal function and 24-hour urine volume were adjusted, IDWG% ≥4.0 remained as a significant predictor of primary outcome (HR 2.03, 95% CI 1.02-4.02, p = 0.04). CONCLUSION: Increased IDWG% is a significant independent predictor of MACCE in incident HD patients. It could be helpful to prevent excessive IDWG for improving clinical outcomes in incident HD patients.

Clinical implication of crescentic lesions in immunoglobulin A nephropathy.

BACKGROUND: To date, there has been much controversy about the role of crescentic lesion as a significant prognostic factor in immunoglobulin A nephropathy (IgAN). This study evaluated whether crescentic lesions predict adverse renal outcomes in IgAN patients. METHODS: A total of 430 patients with biopsy-proven IgAN between January 2000 and December 2009 were included. Histological variables of the Oxford classification (Oxford-MEST) and the presence of crescents were assessed. The primary endpoint was a 50% decline in estimated glomerular filtration rate. RESULTS: Of the 430 patients, 81 (18.8%) had a crescentic lesion. During a mean follow-up of 61 months, the primary outcome occurred in 19 (23.5%) patients with crescents compared with 40 (11.5%) patients without crescents (P=0.01). A Kaplan-Meier plot showed that the 10-year renal survival rate was significantly lower in patients with crescents than patients without crescents (P=0.01). However, in a multivariable Cox analysis which included clinical factors and the Oxford-MEST, crescents were not significantly associated with an increased risk of developing the primary outcome [hazard ratio: 0.71, 95% confidence interval (CI) 0.36-1.41, P=0.33]. Furthermore, adding crescents to the Oxford-MEST did not improve the discriminative ability for the prediction of renal outcomes [c-statistic: 0.86 (0.81-0.91) vs. 0.86 (0.80-0.91), P=0.21]. CONCLUSION: Crescentic lesion was not an independent prognostic factor, suggesting that crescents have limited value in predicting renal outcomes of IgAN.

Circulating α-klotho levels in CKD and relationship to progression.

BACKGROUND: α-Klotho is reported to have protective effects against kidney injury, and its renal expression is decreased in many experimental models of kidney disease. However, circulating α-klotho levels in human chronic kidney disease (CKD) and the relationship to progression are unknown. STUDY DESIGN: Post hoc analysis of a prospective cohort study. SETTING & PARTICIPANTS: 243 of 301 participants from a CKD cohort at our institution between January 2006 and December 2011 were eligible for the study. PREDICTOR: Baseline α-klotho levels. OUTCOMES: Primary outcome was the composite of doubling of baseline serum creatinine concentration, end-stage renal disease, or death. End-stage renal disease was defined as onset of treatment by renal replacement therapy. MEASUREMENTS: Serum α-klotho and fibroblast growth factor 23 (FGF-23) were measured using enzyme-linked immunosorbent assay. RESULTS: Lower serum α-klotho levels were associated with more severe CKD stage in the cross-sectional analysis of the baseline data (P for trend < 0.001). In the adjusted multivariable linear regression model, log(α-klotho) was associated independently with estimated glomerular filtration rate (ß = 0.154; P = 0.001). Cox regression analysis showed that baseline α-klotho level independently predicted the composite outcome after adjustment for age, diabetes, blood pressure, estimated glomerular filtration rate, proteinuria, parathyroid hormone level, and FGF-23 level (HR per 10-pg/mL increase, 0.96; 95% CI, 0.94-0.98; P < 0.001). When patients were categorized into 2 groups according to baseline median α-klotho value, 43 (35.2%) patients with α-klotho levels ≤396.3 pg/mL reached the primary composite outcome compared with 19 (15.7%) with α-klotho levels >396.3 pg/mL (HR, 2.03; 95% CI, 1.07-3.85; P = 0.03). LIMITATIONS: Uncontrolled dietary phosphorus intake and use of frozen samples. CONCLUSIONS: This observational study showed that low circulating α-klotho levels were associated with adverse kidney disease outcome, suggesting that α-klotho is a novel biomarker for CKD progression. More data from larger prospective longitudinal studies are required to validate our findings.

Diastolic dysfunction is associated with an increased risk of contrast-induced nephropathy: a retrospective cohort study.

BACKGROUND: Contrast-induced nephropathy (CIN) is the third leading cause of hospital-acquired acute kidney injury, and it is associated with poor long-term clinical outcomes. Although systolic heart failure is a well-known risk factor for CIN, no studies have yet evaluated the association between diastolic dysfunction and CIN. METHODS: We conducted a retrospective study of 735 patients who underwent percutaneous transluminal coronary angioplasty (PTCA) and had an echocardiography performed within one month of the procedure at our institute, between January 2009 and December 2010. CIN was defined as an increase of ≥ 0.5 mg/dL or ≥ 25% in serum creatinine level during the 72 hours following PTCA. RESULTS: CIN occurred in 64 patients (8.7%). Patients with CIN were older, had more comorbidities, and had an intra-aortic balloon pump (IABP) placed more frequently during PTCA than patients without CIN. They showed greater high-sensitivity C-reactive protein (hs-CRP) levels and lower estimated glomerular filtration rates (eGFR). Echocardiographic findings revealed lower ejection fraction and higher left atrial volume index and E/E' in the CIN group compared with non-CIN group. When patients were classified into 3 groups according to the E/E' values of 8 and 15, CIN occurred in 42 (21.6%) patients in the highest tertile compared with 20 (4.0%) in the middle and 2 (4.3%) in the lowest tertile (p < 0.001). In multivariate logistic regression analysis, E/E' > 15 was identified as an independent risk factor for the development of CIN after adjustment for age, diabetes, dose of contrast media, IABP use, eGFR, hs-CRP, and echocardiographic parameters [odds ratio (OR) 2.579, 95% confidence interval (CI) 1.082-5.964, p = 0.035]. In addition, the area under the receiver operating characteristic curve of E/E' was 0.751 (95% CI 0.684-0.819, p < 0.001), which was comparable to that of ejection fraction and left atrial volume index (0.739 and 0.656, respectively, p < 0.001). CONCLUSIONS: This study demonstrated that, among echocardiographic variables, E/E' was an independent predictor of CIN. This in turn suggests that diastolic dysfunction may be a useful parameter in CIN risk stratification.

The effect of HMG-CoA reductase inhibitor on insulin resistance in patients undergoing peritoneal dialysis.

BACKGROUND: Insulin resistance is associated with the progression of atherosclerosis and is reported to predict cardiovascular mortality in patients with end-stage renal disease (ESRD). Although statins exert pleiotropic effects, it is uncertain whether statin therapy improves insulin resistance in these patients. In this prospective randomized controlled trial, we aimed to evaluate the effects of statin on insulin resistance among 70 patients undergoing peritoneal dialysis (PD). METHODS: Patients were randomized into a statin group (n = 35) or a control group (n = 35). The statin group received 10 mg per day of rosuvastatin for 6 months. We determined insulin resistance by homeostatic model assessment of insulin resistance (HOMA-IR) index. Serum concentrations of adipokines such as adiponectin, leptin, and resistin were measured using enzyme-linked immunosorbent (ELISA) assay. As inflammatory markers, high sensitive C-reactive protein (hsCRP) and interleukin-6 were also measured. RESULTS: There were no significant differences in baseline characteristics between the two groups. Compared to baseline value, statin treatment significantly decreased HOMA-IR index from 2.37 ± 1.08 to 2.05 ± 0.82 (P = 0.014). There was a concordant decrease in hsCRP levels in the statin group (2.05 ± 1.57 to 1.21 ± 0.84 mg/L, P < 0.001), but such improvements were not observed in the control group. When between-group differences in these parameters were compared, hsCRP levels were more decreased in the statin group than in the control group (P = 0.021 for between-group difference), whereas HOMA-IR index was not (P = 0.189 for between-group difference). During this period, statin treatment did not result in the improved adipokine profiles. CONCLUSION: This study showed that statin therapy failed to improve insulin resistance in PD patients despite a significant decline in hsCRP levels after statin treatment. Our finding suggests that reducing inflammation by statin is of limited help to fully attenuate insulin resistance in these patients.

Changes in echocardiographic parameters according to the rate of residual renal function decline in incident peritoneal dialysis patients.

Residual renal function (RRF) is associated with left ventricular (LV) hypertrophy as well as all-cause and cardiovascular (CV) mortality in patients with end-stage renal disease. However, no studies have yet examined the serial changes in echocardiographic findings according to the rate of RRF decline in incident dialysis patients. A total of 81 patients who started peritoneal dialysis (PD) between 2005 and 2012 at Yonsei University Health System, Seoul, South Korea, and who underwent baseline and follow-up echocardiography within the first year of PD were recruited. Patients were dichotomized into "faster" and "slower" RRF decline groups according to the median values of RRF decline slope (-1.60 mL/min/y/1.73 m(2)). Baseline RRF and echocardiographic parameters were comparable between the 2 groups. During the first year of PD, there were no significant changes in LV end-diastolic volume index (LVEDVI), left atrial volume index (LAVI), or LV mass index (LVMI) in the "faster" RRT decline group, while these indices decreased in the "slower" RRT decline group. The rate of RRF decline was a significant determinant of 1-year changes in LVEDVI, LAVI, and LVMI. The linear mixed model further confirmed that there were significant differences in the changes in LVEDVI, LAVI, and LVMI between the 2 groups (P = 0.047, 0.048, and 0.001, respectively). During a mean follow-up duration of 31.9 months, 4 (4.9%) patients died. Compared with the "slower" RRF decline group, CV composite (20.29/100 vs 7.18/100 patient-years [PY], P = 0.098), technique failure (18.80/100 vs 4.19/100 PY, P = 0.006), and PD peritonitis (15.73/100 vs 4.95/100 PY, P = 0.064) developed more frequently in patients with "faster" RRF decline rate. On multivariate Cox regression analysis, patients with "faster" RRF decline rate showed 4.82-, 4.44-, and 7.37-fold higher risks, respectively, for each clinical outcome. Preservation of RRF is important for conserving cardiac performance, resulting in an improvement in clinical outcomes of incident PD patients.

Diastolic dysfunction is an independent predictor of cardiovascular events in incident dialysis patients with preserved systolic function.

BACKGROUND: Diastolic heart failure (HF), the prevalence of which is gradually increasing, is associated with cardiovascular (CV) morbidity and mortality in the general population and, more specifically, in patients with end-stage renal disease (ESRD). However, the impact of diastolic dysfunction on CV outcomes has not been studied in incident dialysis patients with preserved systolic function. METHODS: This prospective observational cohort study investigates the clinical consequence of diastolic dysfunction and the predictive power of diastolic echocardiographic parameters for CV events in 194 incident ESRD patients with normal or near normal systolic function, who started dialysis between July 2008 and August 2012. RESULTS: During a mean follow-up duration of 27.2 months, 57 patients (29.4%) experienced CV events. Compared to the CV event-free group, patients with CV events had a significantly higher left ventricular (LV) mass index, ratio of early mitral flow velocity (E) to early mitral annulus velocity (E') (E/E'), LA volume index (LAVI), deceleration time, and right ventricular systolic pressure, and a significantly lower LV ejection fraction and E'. In multivariate Cox proportional hazard analysis, E/E'>15 and LAVI>32 mL/m2 significantly predicted CV events (E/E'>15: hazard ratio [HR] = 5.40, 95% confidence interval [CI] = 2.73-10.70, P< .001; LAVI>32 mL/m2: HR = 5.56, 95% CI = 2.28-13.59, P< .001]. Kaplan-Meier analysis revealed that patients with both E/E'>15 and LAVI>32 mL/m2 had the worst CV outcomes. CONCLUSION: An increase in E/E' or LAVI is a significant risk factor for CV events in incident dialysis patients with preserved LV systolic function.

Decreased circulating klotho levels in patients undergoing dialysis and relationship to oxidative stress and inflammation.

INTRODUCTION: It has been reported that klotho deficiency is associated with oxidative stress and inflammation in experimental kidney disease models. Patients with endstage renal disease (ESRD) are particularly characterized by increased oxidative stress and inflammation. However, little is known about the relationship between these features and klotho in patients with ESRD. METHODS: We conducted a single-center, cross-sectional study of 78 patients receiving peritoneal dialysis (PD). Serum concentrations of klotho, high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and 8-isoprostane were measured by enzyme-linked immunosorbent assay. To define factors independently associated with klotho, we determined Spearman's correlation coefficients for between co-variates and conducted multiple linear regression analyses. RESULTS: Patients were classified by median concentration of klotho. In patients with klotho levels > 329.6 pg/mL, serum 8-isoprostane and IL-6 levels were significantly higher than in those with klotho levels < 329.6 pg/mL. In correlation analyses, log 8-isoprostane (γ = -0.310, p = 0.006) and log IL-6 (γ = -0.343, p = 0.002) were inversely correlated with log klotho. After adjustment for age, gender, mean arterial pressure, log intact parathyroid hormone, and log IL-6, log 8-isoprostane was independently associated with log klotho (ß = -0.158, p = 0.040). However, the significant relationship between klotho and IL-6 was not seen in an adjusted model. CONCLUSIONS: This study showed that circulating klotho levels were significantly associated with 8-isoprostane levels in patients undergoing PD, suggesting a potential link between klotho deficiency and enhanced oxidative stress in ESRD patients.

Mean platelet volume is a prognostic factor in patients with acute kidney injury requiring continuous renal replacement therapy.

PURPOSE: Platelet size has been demonstrated to reflect platelet activity and to predict poor clinical outcomes in patients with cardiovascular disease. However, the prognostic value of platelet size for mortality has not been studied in patients with acute kidney injury (AKI). MATERIALS AND METHODS: A total of 349 patients who received continuous renal replacement therapy (CRRT) for AKI between August 2009 and October 2011 were divided into 2 groups based on the median mean platelet volume (MPV) at the time of CRRT initiation. Twenty-eight-day mortality rate was determined using Kaplan-Meier plots and time-dependent receiver operating characteristic curves were constructed. In addition, multivariate Cox analysis for mortality was used to evaluate the independent prognostic value of MPV. RESULTS: The mean age was 61.3 years, and 218 patients (62.5%) were male. At the initiation of CRRT, MPV level was inversely correlated with platelet count, whereas it was positively associated with Acute Physiology and Chronic Health Evaluation II scores. During the study period, 231 deaths (66.2%) occurred. Kaplan-Meier curve showed that 28-day all-cause mortality was significantly higher in patients with MPV≥10.2 fL compared with those with MPV<10.2 fL (P<.001). Moreover, Cox regression analysis revealed that MPV was an independent predictor for 28-day all-cause mortality after adjustment of age, age-adjusted Charlson Comorbidity Index, cause of AKI, platelet count, Acute Physiology and Chronic Health Evaluation II score, presence of malignancy, albumin, and C-reactive protein (hazard ratio, 1.080; 95% confidence interval, 1.010-1.155; P=.023). CONCLUSION: Mean platelet volume at the time of CRRT initiation may be an inexpensive and useful predictor for 28-day all-cause mortality in patients with AKI requiring CRRT.

The relationship of initial transferrin saturation to cardiovascular parameters and outcomes in patients initiating dialysis.

BACKGROUND: The prognostic importance of anemia for cardiovascular (CV) events and mortality has been extensively investigated. However, little is known about the impact of transferrin saturation (TSAT), a marker reflecting the availability of iron for erythropoiesis, on clinical outcome in dialysis patients. METHODS: A total of 879 anemic incident dialysis patients were recruited from the Clinical Research Center for End-Stage Renal Disease in Korea and were divided into 3 groups according to baseline TSAT of ≤20%, 20-40%, and >40%. RESULTS: There were no differences in hemoglobin levels and the proportion of patients on erythropoiesis-stimulating agents or iron supplements among the 3 groups. During a mean follow-up duration of 19.3 months, 51 (5.8%) patients died. CV composite (11.71 vs. 5.55 events/100 patient-years, P = 0.001) and all-cause mortality rates (5.38 vs. 2.31 events/100 patient-years, P = 0.016) were significantly higher in patients with TSAT ≤20% compared to those with TSAT 20-40% (reference group). Cox regression analysis revealed that patients with TSAT ≤20% had 1.62- and 2.19-fold higher risks for CV composite outcome (P = 0.046) and all-cause mortality (P = 0.030). Moreover, TSAT ≤20% was significantly associated with left ventricular hypertrophy [odds ratio (OR)  = 1.46], high-sensitivity C-reactive protein ≥3 mg/dL (OR = 2.09), N-terminal pro B-type natriuretic peptide ≥10000 pg/mL (OR  = 2.04), and troponin-T≥0.1 ng/mL (OR  = 2.02), on logistic regression analysis. CONCLUSIONS: Low TSAT was a significant independent risk factor for adverse clinical outcome in incident dialysis patients with anemia, which may be partly attributed to cardiac dysfunction and inflammation.

Effect of peritoneal dialysis modality on the 1-year rate of decline of residual renal function.

PURPOSE: The effect of different peritoneal dialysis (PD) modalities on the decline in residual renal function (RRF) is unclear due to inconsistencies among studies. In particular, the effect of automated peritoneal dialysis (APD) modalities [continuous cyclic peritoneal dialysis (CCPD) and nightly intermittent peritoneal dialysis (NIPD)] on RRF has not been examined in a large cohort. MATERIALS AND METHODS: We conducted a single-center retrospective study to investigate the association between PD modalities and decline in RRF in 142 incident PD patients [34 on CCPD, 36 on NIPD, and 72 on continuous ambulatory peritoneal dialysis (CAPD)]. RRF was measured within 2 months from PD start and at 1 year after PD initiation. RESULTS: The RRF at 1 year after PD initiation was 1.98±2.20 mL/min/1.73 m² in CCPD patients and 3.63±3.67 mL/min/1.73 m² in NIPD patients, which were moderately lower than 4.23±3.51 mL/min/1.73 m² in CAPD patients (p=0.064). Moreover, there was no significant difference in the 1-year rate of decline of RRF between CCPD and NIPD patients, although APD patients had a faster 1-year RRF decline rate than CAPD patients (CCPD and NIPD vs. CAPD: -45.68 and -36.69 vs. 1.17%/year, p=0.045). APD was associated with a more rapid decline in RRF in patients with end-stage renal disease undergoing PD, although multivariate analysis attenuated the significance of this finding (ß=-31.50; 95% CI, -63.61 to 0.62; p=0.052). CONCLUSION: Our results suggest that CAPD might be more helpful than APD for preserving RRF during the first year of dialysis therapy, although there was no significant difference in the 1-year rate of decline of RRF between the two APD modalities.

Comparison of the Haas and the Oxford classifications for prediction of renal outcome in patients with IgA nephropathy.

Pathologic features can provide valuable information for determining prognosis in IgA nephropathy (IgAN). However, it is uncertain whether the Oxford classification, a new classification of IgAN, can predict renal outcome better than previous ones. We conducted a retrospective cohort study in 500 patients with biopsy-proven IgAN between January 2002 and December 2010 to compare the ability of the Haas and the Oxford classifications to predict renal outcome. Primary outcome was a doubling of the baseline serum creatinine concentration (D-SCr). During a mean follow-up of 68 months, 52 (10.4%) and 35 (7.0%) developed D-SCr and end-stage renal disease, respectively. There were graded increases in the development of D-SCr in the higher Haas classes. In addition, the primary endpoint of D-SCr occurred more in patients with the Oxford M and T lesions than those without such lesions. In multivariate Cox regression analyses, the Haas class V (HR, 12.19; P=.002) and the Oxford T1 (hazard ratio [HR], 6.68; P<.001) and T2 (HR, 12.16; P<.001) lesions were independently associated with an increased risk of reaching D-SCr. Harrell's C index of each multivariate model with the Haas and the Oxford classification was 0.867 (P=.015) and 0.881 (P=.004), respectively. This was significantly higher than that of model with clinical factors only (C=0.819). However, there was no difference in C-statistics between the 2 models with the Haas and the Oxford classifications (P=.348). This study suggests that the Haas and the Oxford classifications are comparable in predicting progression of IgAN.

Thyroid hormone replacement therapy attenuates the decline of renal function in chronic kidney disease patients with subclinical hypothyroidism.

BACKGROUND: Subclinical hypothyroidism (SCH) is not a rare condition in females, the elderly, or patients with chronic kidney disease (CKD). Even though previous studies have demonstrated that thyroid hormone replacement therapy (THRT) improves cardiac function and dyslipidemia in patients with SCH, it remains unclear as to whether THRT can improve renal function in CKD patients with SCH. This study investigated the impact of THRT on changes in estimated glomerular filtration rates (eGFR) in this patient population. METHODS: A total of 113 CKD patients with SCH who were treated with L-thyroxine and had eGFR available for at least 24 months before and after THRT were enrolled between January 2005 and December 2011. A linear mixed model was used to compare patients' clinical and biochemical parameters at various time points. The slope of the decline in eGFR over time, both before and after THRT, was also calculated and compared using a linear mixed model. RESULTS: The mean age of the study participants was 63.2±12.7 years, and 36 patients (31.9%) were men. The mean follow-up duration before and after THRT was 28.6±4.5 and 30.6±6.4 months respectively. After 24 months of THRT, serum thyrotropin (TSH) levels were significantly reduced-8.86±0.49 versus 1.41±0.73 µIU/mL, p<0.001-but there were no significant changes in triiodothyronine and free thyroxine concentrations. Serum albumin, calcium, phosphate, cholesterol, and triglyceride levels were also comparable before and after THRT. The rates of decline in eGFR were significantly attenuated by THRT (-4.31±0.51 vs.-1.08±0.36 [mL/min]/[year·1.73 m²], p<0.001), even after adjustment for age, sex, diabetes, mean arterial pressure, and serum albumin, cholesterol, and triglyceride concentrations (p<0.001). CONCLUSION: THRT attenuated the rate of decline in renal function in CKD patients with SCH, suggesting that THRT may delay reaching end-stage renal disease in these patients.

Stepwise treatment using corticosteroids alone and in combination with cyclosporine in korean patients with idiopathic membranous nephropathy.

PURPOSE: We undertook an observational study to investigate the effects of immunosuppressive treatment on proteinuria and renal function in 179 Korean idiopathic membranous nephropathy patients with nephrotic syndrome. MATERIALS AND METHODS: The primary outcome was regarded as the first appearance of remission and the secondary outcomes as a decline in estimated glomerular filtration rate (eGFR) >50% or initiation of dialysis, and all-cause mortality. Seventy-two (40.2%) and 50 (27.9%) patients were treated with corticosteroids alone (C) and corticosteroids plus cyclosporine (C+C), respectively, whereas 57 (31.8%) did not receive immunosuppressants (NTx). Cyclosporine was added if there was no reduction in proteinuria of >50% from baseline by corticosteroids alone within 3 months. RESULTS: There were no differences in baseline renal function and the amount of proteinuria among the three groups. Overall, complete remission (CR) was achieved in 88 (72.1%) patients by immunosuppressants. In a multivariate analysis adjusted for covariates associated with adverse renal outcome, the probability of reaching CR was significantly higher in the C [hazard ratio (HR), 4.09; p<0.001] and C+C groups (HR, 2.57; p=0.003) than in the NTx group. Kaplan-Meier analysis revealed that 5-year CR rates of C, C+C, and NTx groups were 88.5%, 86.2%, and 56.7% (p<0.001). Ten-year event-free rates for the secondary endpoints in these three groups were 91.7%, 79.9%, and 57.2% (p=0.01). CONCLUSION: Immunosuppressive treatment was effective in inducing remission and preserving renal function in these patients. Therefore, stepwise treatment using corticosteroids alone and in combination with cyclosporine is warranted in these patients.

Membranous glomerulonephritis in a patient with myelodysplastic syndrome-refractory cytopenia with multilineage dysplasia.

A 74-year-old woman presented with edema in the lower extremities. Laboratory tests revealed anemia, thrombocytopenia, hypoalbuminemia, hypercholesterolemia, and nephrotic-range proteinuria. Myelodysplastic syndrome-refractory cytopenia with multilineage dysplasia (MDS-RCMD) was confirmed by bone marrow biopsy. Renal biopsy demonstrated membranous glomerulonephritis (MGN), stage I. Based on these clinicopathologic results, she was diagnosed as having MGN with MDS-RCMD. This is a rare case report of MGN in a parient with MDS-RCMD featuring nephrotic syndrome.

The impact of low triiodothyronine levels on mortality is mediated by malnutrition and cardiac dysfunction in incident hemodialysis patients.

OBJECTIVE: Little is known about the impact of low triiodothyronine (T3) levels on mortality in end-stage renal disease (ESRD) patients starting hemodialysis (HD) and whether this impact is mediated by malnutrition, inflammation, or cardiac dysfunction. DESIGN AND METHODS: A prospective cohort of 471 incident HD patients from 36 dialysis centers within the Clinical Research Center for ESRD in Korea was selected for this study. Based on the median value of T3, patients were divided into 'higher' and 'lower' groups, and all-cause and cardiovascular (CV) mortality rates were compared. In addition, associations between T3 levels and various nutritional, inflammatory, and echocardiographic parameters were determined. RESULTS: Compared with those in the 'higher' T3 group, albumin, cholesterol, and triglyceride levels, lean body mass estimated by creatinine kinetics (LBM-Cr), and normalized protein catabolic rate (nPCR) were significantly lower in patients with 'lower' T3 levels. The 'lower' T3 group also had a higher left ventricular mass index (LVMI) and a lower ejection fraction (EF). Furthermore, correlation analysis revealed significant associations between T3 levels and nutritional and echocardiographic parameters. All-cause and CV mortality rates were significantly higher in patients with 'lower' T3 levels than in the 'higher' T3 group (113.4 vs 18.2 events per 1000 patient-years, P<0.001, and 49.8 vs 9.1 events per 1000 patient-years, P=0.001, respectively). The Kaplan-Meier analysis also showed significantly worse cumulative survival rates in the 'lower' T3 group (P<0.001). In the Cox regression analysis, low T3 was an independent predictor of all-cause mortality even after adjusting for traditional risk factors (hazard ratio=3.76, P=0.021). However, the significant impact of low T3 on all-cause mortality disappeared when LBM-Cr, nPCR, LVMI, or EF were incorporated into the models. CONCLUSION: Low T3 has an impact on all-cause mortality in incident HD patients, partly via malnutrition and cardiac dysfunction.

Association between the ratio of insulin-like growth factor-I to insulin-like growth factor binding protein-3 and inflammation in incident automated peritoneal dialysis patients.

BACKGROUND: The insulin-like growth factor (IGF) system is known to be associated with inflammation in various populations. However, the association between the IGF system and inflammation has not previously been investigated in automated peritoneal dialysis (APD) patients. Therefore, the aim of this study was to investigate whether the IGF system correlates with inflammation in APD patients. METHODS: We prospectively determined IGF-I activity, the ratio of serum IGF-I concentrations to those of IGF binding protein-3 (IGFBP-3), and inflammatory markers at initiation of APD and after 6 months of follow-up in 21 incident APD patients. RESULTS: The mean age was 55.2 ± 13.1 years, and 11 patients (52.3%) were male. Continuous cyclic PD (CCPD) was performed in 11 patients, and nocturnal intermittent PD (NIPD) in 10 patients. The mean value of IGF-I/IGFBP-3 was 0.21 ± 0.13. At baseline, IGF-I/IGFBP-3 was negatively correlated with high-sensitivity C-reactive protein (hs-CRP) (r = -0.27, P = 0.032) and interleukin-6 (IL-6) (r = -0.19, P = 0.046) concentrations. After 6 months, IGF-I/IGFBP-3 (P = 0.048) had decreased significantly, while the hs-CRP (P = 0.036) increased significantly in the CCPD group. However, there were no significant changes in IGF-I/IGFBP-3 (P = 0.59) and hs-CRP (P = 0.14) during 6 months in the NIPD group. Furthermore, compared with the NIPD group, IGF-I/IGFBP-3 (P = 0.041) decreased greater, whereas hs-CRP (P = 0.048) concentrations increased greater in the CCPD group. CONCLUSIONS: The IGF system was significantly associated with inflammatory markers in incident APD patients, and different APD modalities modulate the IGF system and inflammation.

Sagittal abdominal diameter is an independent predictor of all-cause and cardiovascular mortality in incident peritoneal dialysis patients.

BACKGROUNDS AND AIMS: Visceral fat has a crucial role in the development and progression of cardiovascular disease, the major cause of death in end-stage renal disease (ESRD). Although sagittal abdominal diameter (SAD), as an index of visceral fat, significantly correlated with mortality in the general population, the impact of SAD on clinical outcomes has never been explored in ESRD patients. Therefore, we sought to elucidate the prognostic value of SAD in incident peritoneal dialysis (PD) patients. METHODS: We prospectively determined SAD by lateral abdominal X-ray at PD initiation, and evaluated the association of SAD with all-cause and cardiovascular mortality in 418 incident PD patients. RESULTS: The mean SAD was 24.5 ± 4.3 cm, and during a mean follow-up of 39.4 months, 97 patients (23.2%) died, and 49.4% of them died due to cardiovascular disease. SAD was a significant independent predictor of all-cause [3rd versus 1st tertile, HR (hazard ratio): 3.333, 95% CI (confidence interval): 1.514-7.388, P = 0.01; per 1 cm increase, HR: 1.071, 95% CI: 1.005-1.141, P = 0.03] and cardiovascular mortality (3rd versus 1st tertile, HR: 8.021, 95% CI: 1.994-32.273, P = 0.01; per 1 cm increase, HR: 1.106, 95% CI: 1.007-1.214, P = 0.03). Multivariate fractional polynomial analysis also showed that all-cause and cardiovascular mortality risk increased steadily with higher SAD values. In addition, SAD provided higher predictive value for all-cause (AUC: 0.691 vs. 0.547, P<0.001) and cardiovascular mortality (AUC: 0.644 vs. 0.483, P<0.001) than body mass index (BMI). Subgroup analysis revealed higher SAD (≥ 24.2 cm) was significantly associated with all-cause mortality in men, women, younger patients (<65 years), and patients with lower BMI (<22.3 kg/m(2)). CONCLUSIONS: SAD determined by lateral abdominal X-ray at PD initiation was a significant independent predictor of all-cause and cardiovascular mortality in incident PD patients. Estimating visceral fat by SAD could be useful to stratify mortality risk in these patients.