The difference between cystatin C- and creatinine-based eGFR is associated with adverse cardiovascular outcome in patients with chronic kidney disease.

BACKGROUND AND AIMS: Decreased kidney function is an important risk factor for cardiovascular disease (CVD). However, assessing risk of CVD may be difficult when there is a gap between creatinine- and cystatin C-based estimated glomerular filtration rate (eGFR). We studied the association of the difference in eGFRs with major adverse cardiovascular events (MACE) in patients with chronic kidney disease (CKD). METHODS: This prospective cohort study was conducted in 2076 patients with CKD stages based on the KDIGO guideline (eGFR categories of G1: ≥90; G 2: 60-89; G3: 30-59; G4: 15-29; G5: <15 mL/min/1.73 m2 without kidney replacement therapy). The difference in eGFR (eGFRdiff) was calculated by subtracting the cystatin C-based eGFR (eGFRcys) from the creatinine-based eGFR (eGFRcreat). The primary outcome was MACE, defined as non-fatal acute myocardial infarction and unstable angina, stroke, congestive heart failure, symptomatic arrhythmia, and cardiac death. RESULTS: During a median follow-up of 4.1 years, MACE occurred in 147 patients (incidence rate, 15.0 per 1000 patient-years). When patients were categorized into baseline eGFRdiff tertiles, the highest tertile was associated with a significantly higher risk of MACE (hazard ratio, 2.12; 95% confidence interval [CI], 1.28-3.51) than the lowest tertile when adjusted for eGFRcreat, eGFRcys, or eGFR based on both creatinine and cystatin C. Patients in the highest tertile had more baseline coronary artery calcification (CAC) than those in the lowest tertile (odds ratio [OR], 1.38; 95% CI, 1.03-1.86). In addition, 978 patients had data for both baseline and follow-up CAC at year 4. In this subgroup, baseline eGFRdiff was significantly associated with accelerated CAC progression (≥50/year) (OR, 1.03; 95% CI, 1.01-1.05). CONCLUSIONS: A large positive difference between eGFRcreat and eGFRcys was associated with a higher risk of MACE and faster CAC progression in patients with CKD. Therefore, careful monitoring of CVD is needed for patients with a higher eGFRdiff.

Smoking Cessation and Coronary Artery Calcification in CKD.

BACKGROUND AND OBJECTIVES: Smoking is associated with vascular calcification and a higher risk of cardiovascular disease. In this study, we investigated the association of smoking dose and cessation with coronary artery calcification (CAC) in patients with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: From a nationwide, prospective cohort of Korean patients with CKD, 1914 participants were included. Prevalent CAC was defined as an Agatston score >0, using computed tomography. CAC progression was defined as ≥30%/yr increase in Agatston score at the 4-year follow-up examination in patients with baseline CAC. RESULTS: Prevalent CAC was observed in 952 (50%) patients. Compared with never smokers, former smokers had a similar prevalence ratio for CAC, but current smokers had a 1.25-fold higher prevalence ratio (95% confidence interval [95% CI], 1.10 to 1.42). Among former smokers, a lower smoking load of <10 pack-years (prevalence ratio, 0.77; 95% CI, 0.65 to 0.90) and longer duration of smoking cessation (prevalence ratio for 10 to <20 years, 0.85; 95% CI, 0.73 to 0.98: prevalence ratio for ≥20 years, 0.83; 95% CI, 0.73 to 0.96) were associated with lower risk of prevalent CAC compared with current smoking. The prevalence ratios did not differ between never smoking and long-term cessation. However, short-term cessation with heavy smoking load was associated with a higher risk of prevalent CAC (prevalence ratio, 1.21; 95% CI, 1.03 to 1.40) compared with never smoking. CAC progression was observed in 111 (33%) patients with baseline CAC. Compared with never smokers, former smokers showed a similar risk of CAC progression, but current smokers had a higher risk (relative risk, 1.92; 95% CI, 1.30 to 2.86). CONCLUSIONS: In CKD, former smoking with a lower smoking load and long-term cessation were associated with a lower risk of prevalent CAC than current smoking. CAC progression was more pronounced in current smokers.

Association between the transtubular potassium gradient and progression of chronic kidney disease: results from KNOW-CKD.

BACKGROUND: The transtubular potassium gradient which reflects potassium secretion by the kidney through the cortical collecting duct, has not yet been tested as a surrogate marker of kidney function decline. Here, we investigate the relationship between the transtubular potassium gradient and chronic kidney disease (CKD) progression. METHODS: We studied 1672 patients from the KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease (KNOW-CKD) cohort. The transtubular potassium gradient was calculated using a standard equation. The study endpoint was CKD progression, defined as a composite of a ≥ 50% decrease in estimated glomerular filtration rate (eGFR) from baseline values or end-stage kidney disease. RESULTS: During a median follow-up of 4.1 years (7149 person-years), 441 participants reached the endpoint. In cause-specific competing risk analysis, the highest tertile was associated with a significantly lower risk of an adverse kidney outcome compared with the lowest tertile [hazard ratio (HR), 0.73; 95% confidence interval (CI), 0.55-0.97]. When the transtubular potassium gradient was treated as a continuous variable, an increase of 1 in the transtubular potassium gradient was associated with a 6% lower risk of CKD progression (95% CI, 0.90-0.99). This association was particularly evident in patients with an eGFR ≥ 45 mL/min/1.73 m2. A time-updated transtubular potassium gradient model showed similar results. The predictive performance of the transtubular potassium gradient was significantly less than that of the eGFR, but similar to that of proteinuria, serum bicarbonate, and urine osmolality. CONCLUSIONS: A higher transtubular potassium gradient is associated with a significantly lower risk of CKD progression, suggesting that it may offer insights into the prognosis of CKD.

Smoking, Smoking Cessation, and Progression of Chronic Kidney Disease: Results From KNOW-CKD Study.

INTRODUCTION: In patients with chronic kidney disease (CKD), studies investigating the association between smoking and deterioration of kidney function are scarce. AIMS AND METHODS: We analyzed data for 1,951 patients with an estimated glomerular filtration rate (eGFR) ≥15 mL/min/1.73 m2 enrolled in the KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD) from 2011 to 2016. Patients were categorized by smoking load. Primary outcome was a composite of a ≥50% reduction in eGFR, initiation of dialysis, or kidney transplantation. RESULTS: There were 967 never-smokers and 369, 276, and 339 smokers who smoked <15, 15 to 29, ≥30 pack-years, respectively. During a mean follow-up of 3.0 years, the incidence rates (95% confidence interval [CI]) of the primary outcome were 54.3 (46.4-63.5), 46.9 (35.9-61.4), 69.2 (52.9-90.6), and 76.3 (60.7-96.0) events per 1,000 person-yr in never-, <15, 15 to 29, and ≥30 pack-year smokers. In cause-specific hazard model after adjustment of confounding factors, smokers were associated with 1.09 (0.73-1.63), 1.48 (1.00-2.18), and 1.94 (1.35-2.77) fold increased risk (95% CI) of primary outcome in <15, 15-29, and ≥30 pack-year smokers compared with never-smokers. The association of longer smoking duration with higher risk of CKD progression was evident particularly in patients with eGFR < 45 mL/min/1.73 m2 and proteinuria ≥ 1.0 g/g. In contrast, the risk of adverse kidney outcome decreased with longer smoking-free periods among former-smokers. CONCLUSIONS: These findings suggest potentially harmful effects of the degree of exposure to smoking on the progression of CKD. IMPLICATIONS: Among patients with CKD, there has been lack of studies on the association between smoking and CKD progression and studies to date have yielded conflicting results. In this prospective cohort study involving Korean CKD patients, smoking was associated with significantly higher risk of worsening kidney function. Furthermore, the risk of adverse kidney outcome was incrementally higher as smoking pack-years were higher. As the duration of smoking cessation increased, the hazard ratios for adverse kidney outcome were attenuated, suggesting that quitting smoking may be a modifiable factor to delay CKD progression.

eGFR and coronary artery calcification in chronic kidney disease.

BACKGROUND: The independent association between eGFR and coronary artery calcification (CAC) is complex and not clear. The aim of this study was to investigate the relationship between eGFR calculated from different equations and CAC in predialysis CKD patients in Korea. METHODS: In this cross-sectional study, we analysed 1533 patients from the KNOW-CKD cohort. eGFR was calculated by a four-variable MDRD equation (eGFRMDRD ), CKD-EPI creatinine equations (eGFRCr ), CKD-EPI cystatin C equation (eGFRCys ) and CKD-EPI creatinine-cystatin equation (eGFRCrCys ). Participants were divided into eGFR categories (<30, 30-59, 60-89, ≥90 mL/min/1.73 m2 ). CACS (coronary artery calcium score) was measured using cardiac computed tomography. CAC was defined as CACS >100. RESULTS: Coronary artery calcification was found in 334 (21.8%) patients and was more prevalent in the lower eGFR groups (P < 0.001). In multivariate Tobit regression, CACS increased gradually as eGFRCrCys decreased (P for trend = 0.034). In multivariate logistic regression, there were gradual associations between lower eGFR and CAC when an eGFRCys or eGFRCrCys was used. The adjusted OR for CAC in the group with eGFR <30 mL/min/1.73 m2 compared to the group with eGFR ≥90 mL/min/1.73 m2 was 2.64 (95% CI, 1.09-3.60) when eGFRCrCys was used. Of the four eGFR formulas, only adding eGFRCrCys significantly improved CAC prediction models without eGFR (P = 0.046). CONCLUSIONS: There was a gradual and independent association between low eGFR and CAC in a predialysis CKD cohort in Korea. eGFRCrCys predicted CAC better than other equations in this population.

High fibroblast growth factor 23 is associated with coronary calcification in patients with high adiponectin: analysis from the KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD) study.

Background: The association between fibroblast growth factor 23 (FGF23) and coronary artery calcification (CAC) was inconclusive. Recently it was shown that adiponectin modulates renal handling of calcium and phosphorus. We hypothesized that adiponectin plays a role in the effect of FGF23 on CAC and explored whether the association between FGF23 and CAC is modified by serum adiponectin level in chronic kidney disease (CKD) patients. Methods: This cross-sectional study analyzed 1435 predialysis CKD patients from the Korean Cohort Study for Outcome in Patients with CKD cohort. Participants were divided into two groups according to their serum adiponectin (upper half and lower half). Each group was further divided into three groups according to their FGF23 levels as follows: low (<5.0 RU/mL), middle (5.0-29.9 RU/mL) and high (≥30.0 RU/mL). The coronary artery calcium score (CACS) was assessed using cardiac computed tomography and CAC was defined as a CACS >100. Results: The median CACS did not differ between the low and high adiponectin groups {3.2 [interquartile range (IQR) 0.0-98.1] versus 0.5 [0.0-99.5], P = 0.988}. The CACS ratio comparing high FGF23 to low FGF23 was significantly increased in the high adiponectin group, but not in the low adiponectin group [2.35 (IQR 1.14-4.85) versus 1.10 (0.60-2.03)]. The odds ratio for CAC in the high FGF23 group compared with the low group was 1.97 (IQR 1.10-3.53). The association between FGF23 and CAC was modified significantly by adiponectin level (P for interaction = 0.023). Conclusions: High serum FGF23 was associated with CAC in CKD patients with high adiponectin, but not in those with low adiponectin. Further studies are warranted to verify the role of adiponectin in FGF23-related CAC.

The Correlation of Serum Osteoprotegerin with Non-Traditional Cardiovascular Risk Factors and Arterial Stiffness in Patients with Pre-Dialysis Chronic Kidney Disease: Results from the KNOW-CKD Study.

BACKGROUND: Osteoprotegerin (OPG) plays protective roles against the development of vascular calcification (VC) which greatly contributes to the increased cardiovascular events in patients with chronic kidney disease (CKD). The present study aimed to find the non-traditional, kidney-related cardiovascular risk factors correlated to serum OPG and the effect of serum OPG on the arterial stiffness measured by brachial ankle pulse wave velocity (baPWV) in patients with the pre-dialysis CKD. METHODS: We cross-sectionally analyzed the data from the patients in whom baPWV and the serum OPG were measured at the time of enrollment in a prospective pre-dialysis CKD cohort study in Korea. RESULTS: Along with traditional cardiovascular risk factors such as age, diabetes mellitus, pulse pressure, and baPWV, non-traditional, kidney-related factors such as albuminuria, plasma level of hemoglobin, total CO2 content, alkaline phosphatase, and corrected calcium were independent variables for serum OPG in multivariate linear regression. Reciprocally, the serum OPG was positively associated with baPWV in multivariate linear regression. The baPWV in the 3rd and 4th quartile groups of serum OPG were higher than that in the 1st quartile group after adjustments by age, sex and other significant factors for baPWV in linear mixed model. CONCLUSION: Non-traditional, kidney-related cardiovascular risk factors in addition to traditional cardiovascular risk factors were related to serum level of OPG in CKD. Serum OPG level was significantly related to baPWV. Our study suggests that kidney-related factors involved in CKD-specific pathways for VC play a role in the increased secretion of OPG into circulation in patients with CKD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01630486.

Cystatin C is Better than Serum Creatinine for Estimating Glomerular Filtration Rate to Detect Osteopenia in Chronic Kidney Disease Patients.

PURPOSE: Recent studies have reported that loss of bone mass is associated with renal function decline and increased fracture risks in chronic kidney disease (CKD) patients. The aim of this study was to investigate the best estimated glomerular filtration rate (eGFR) equation to detect osteopenia in CKD patients. MATERIALS AND METHODS: This was a cross-sectional study, and 780 patients aged 50 years or above were classified into normal bone mass or osteopenia groups according to the -1.0 of T-scores at total hip and femur neck. Comparisons of area under the receiver operating characteristic (ROC) curves (AUC) were performed to investigate significant differences among three eGFR formulas: Modification of Diet in Renal Disease, CKD-Epidemiology Collaboration (EPI) creatinine, and CKD-EPI cystatin C (CKD-EPI-Cys). RESULTS: The mean age was 61 years old and the proportion of females was 37.3%. The total hip osteopenia group showed lower CKD-EPI-Cys eGFR levels (osteopenia group, 33.3±19.0 mL/min/1.73 m²; normal group, 48.1±26.2 mL/min/1.73 m², p<0.001). In multiple logistic regression analysis, CKD-EPI-Cys eGFR was independently associated with osteopenia at the total hip (per 1 mL/min/1.73 m² increase, odds ratio 0.98, 95% confidence interval 0.97-0.99, p=0.004) after adjusting for confounding variables. ROC curve analyses indicated that CKD-EPI-Cys shows the largest AUC for osteopenia at the total hip (AUC=0.678, all p<0.01) and the femur neck (AUC=0.665, all p<0.05). CONCLUSION: Decreased renal function assessed by CKD-EPI-Cys equation correlates with osteopenia better than creatinine-based methods in CKD patients, and the CKD-EPI-Cys formula might be a useful tool to assess skeletal-related event risks.

Association of Serum Osteoprotegerin Levels with Bone Loss in Chronic Kidney Disease: Insights from the KNOW-CKD Study.

Osteoprotegerin, a potent osteoclast activation inhibitor, decreases bone resorption and positively affects bone mineral density. This study examined the association between serum osteoprotegerin levels and bone loss in patients with chronic kidney disease, a condition associated with increased risk of mineral and bone disorders. The bone mineral densities of the lumbar spine, total hip, and femur neck were assessed by dual-energy X-ray absorptiometry; serum osteoprotegerin levels were measured at baseline for 1,423 patients enrolled in the prospective KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD). Patients aged ≥50 years and with a T-score ≤ -2.5 were diagnosed as having osteoporosis. Multivariable linear regression analysis indicated independent association between serum osteoprotegerin levels and decreased bone mineral density in the lumbar spine (B: -0.489, 95% confidence interval [CI]: -0.883 to -0.095, P = 0.015), and total hip (B: -0.349, 95% CI: -0.672 to -0.027, P = 0.027). However, bone mineral density of the femur neck was not associated with serum osteoprotegerin levels in women. After adjustments, no independent association was found between serum osteoprotegerin levels and bone mineral density in men. In multivariable logistic regression analysis, serum osteoprotegerin levels were associated with increased risk of osteoporosis in women (odds ratio [OR]: 4.72, 95% CI: 1.35 to 16.52, P = 0.015), but not in men (OR: 0.21; 95% CI: 0.04 to 1.31, P = 0.095). To summarize, in female patients with chronic kidney disease, increased serum osteoprotegerin levels were independently associated with decreased bone mineral density in the lumbar spine and total hip, and with increased risk of osteoporosis. Therefore, the measurement of serum osteoprotegerin concentration might be useful as a surrogate marker for determining bone loss in patients with chronic kidney disease, especially for women, although not so much for men.

Smoking-Related Renal Histologic Injury in IgA Nephropathy Patients.

PURPOSE: Smoking reportedly exerts deleterious effects on renal function; however, its effects on histology have not been clarified in patients with IgA nephropathy (IgAN). MATERIALS AND METHODS: Renal histology was evaluated in a cohort of 397 patients diagnosed with IgAN according to smoking status and dose in relation to renal function. RESULTS: Among the study cohort, which was predominantly male (88.5%), 52 patients (13%) were current smokers. These current smokers demonstrated more frequent hypertension and higher serum creatinine levels than non/ex-smokers at the time of diagnosis, which was apparent with increased smoking dose. The percentages of global glomerulosclerosis and arteriolar hyalinosis increased with increased smoking dose, whereas tubulointerstitial fibrosis or arterial intimal thickening did not. Glomerular mesangial alpha-smooth muscle actin expression were similar between current and non/ex-smokers matched for age, gender, hypertension, and histologic severity, although the number of glomerular CD68+ cells was significantly fewer in smokers. Initial serum creatinine level, estimated glomerular filtration rate (eGFR), and global glomerulosclerosis were found to be risk factors of serum creatinine doubling in both smokers and non/ex-smokers by univariate analysis during a mean follow-up of 3.8 years. CONCLUSION: In addition to dose dependent renal functional decline and hypertension, smoking contributes to renal disease progression by eliciting microvascular injury in IgAN patients.

Glomerular epithelial CD44 expression and segmental sclerosis in IgA nephropathy.

BACKGROUND: CD44 is a marker of activated parietal epithelial cells (PECs), and is expressed in glomerular visceral epithelial cells (VECs) during development of segmental sclerosis. We explored the significance of glomerular epithelial CD44 expression in relation to segmental sclerosis in patients with mild IgA nephropathy (IgAN). METHODS: A total of 126 cases of IgAN were divided into three groups based on glomerular morphology: normal (group A, n = 30), mild mesangial proliferation without segmental sclerosis or synechia (SS) (group B, n = 31), or mild mesangial proliferation with SS (group C, n = 65). The number of CD44-expressing PECs and VECs was counted in each glomerulus and expressed as the mean number per case. RESULTS: CD44 staining was positive in VECs in 59.5 %, in PECs in 79.4 % and in both cell types in 56.3 % of cases. The number of CD44+ PECs or VECs was significantly higher in group C than in groups A or B. Cases with >1 CD44+ cell (PECs and VECs) per glomerulus were associated with increased urine protein/creatinine ratio (UPCr) at last follow-up. The presence of >1 CD44+ VEC/glomerulus was associated with increased UPCr and serum creatinine levels, and decreased estimated glomerular filtration rate (eGFR) even in the absence of SS at the time of biopsy. CONCLUSION: CD44 was expressed in PECs and VECs in association with SS in IgAN. Increased CD44 expression in VECs is a sign of active glomerular injury and dysfunction in these patients.

Optimal proteinuria target for renoprotection in patients with IgA nephropathy.

BACKGROUND: Proteinuria is a target for renoprotection in kidney diseases. However, optimal level of proteinuria reduction in IgA nephropathy (IgAN) is unknown. METHODS: We conducted a retrospective observational study in 500 patients with biopsy-proven IgAN. Time-averaged proteinuria (TA-P) was calculated as the mean of every 6 month period of measurements of spot urine protein-to-creatinine ratio. The study endpoints were a 50% decline in estimated glomerular filtration rate (eGFR), onset of end-stage renal disease (ESRD), and slope of eGFR. RESULTS: During a median follow-up duration of 65 (12-154) months, a 50% decline in eGFR occurred in 1 (0.8%) patient with TA-P of <0.3 g/g compared to 6 (2.7%) patients with TA-P of 0.3-0.99 g/g (hazard ratio, 2.82; P = 0.35). Risk of reaching a 50% decline in eGFR markedly increased in patients with TA-P of 1.0-2.99 g/g (P = 0.002) and those with TA-P≥3.0 g/g (P<0.001). ESRD did not occur in patients with TA-P<1.0 g/g compared to 26 (20.0%) and 8 (57.1%) patients with TA-P of 1.0-2.99 and ≥3.0 g/g, respectively. Kidney function of these two groups deteriorated faster than those with TA-P<1.0 g/g (P<0.001). However, patients with TA-P of 0.3-0.99 g/g had a greater decline of eGFR than patients with TA-P<0.3 g/g (-0.41±1.68 vs. -0.73±2.82 ml/min/1.73 m2/year, P = 0.03). CONCLUSION: In this study, patients with TA-P<1.0 g/g show favorable outcomes. However, given the faster eGFR decline in patients with TA-P of 0.3-0.99 g/g than in patients with TA-P<0.3 g/g, the ultimate optimal goal of proteinuria reduction can be lowered in the management of IgAN.

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.

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.

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.

A case of Tsutsugamushi disease presenting with nephrotic syndrome.

Nephrotic syndrome associated with Tsutsugamushi disease has not been previously reported. We are describing a case of Tsutsugamuchi disease presenting with nephrotic syndrome. A 72-year-old woman presented with fever and generalized edema. Laboratory studies revealed a leukocytosis, hypoalbuminemia, and hypercholesterolemia. Her urine protein excretion was 5.4 g/day. The anti-Tsutsugamushi antibody test was strongly positive (1:2,560). A renal biopsy was performed, and pathologic findings revealed membranous glomerulonephritis. The patient's clinical symptoms improved markedly after treatment with doxycycline.

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.

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.

A case of membranous nephropathy as a manifestation of graft-versus-host disease.

Nephrotic syndrome (NS) rarely occurs after hematopoietic stem cell transplantation (HSCT) as a late manifestation of graft-versus-host disease (GVHD). Herein, we report a case of HSCT-associated membranous nephropathy in a female patient with aplastic anemia. The patient received an allogeneic HSCT from her human leukocyte antigen-identical brother following myeloablative conditioning chemotherapy. NS occurred 21 months after HSCT without any concurrent features of chronic GVHD. The patient was treated with prednisolone and cyclosporine after renal biopsy confirmed membranous nephropathy, and achieved complete remission. Our report contradicts previous assumptions that concomitant chronic GVHD is responsible for the development of NS, suggesting that NS can develop as a new, independent manifestation of GVHD.

Renal histologic parameters influencing postoperative renal function in renal cell carcinoma patients.

BACKGROUND: Pre-existing non-neoplastic renal diseases or lesions may influence patient renal function after tumor removal. However, its description is often neglected or omitted in pathologic reports. To determine the incidence and clinical significance of non-neoplastic lesions, we retrospectively examined renal tissues obtained during 85 radical nephrectomies for renal cell carcinoma. METHODS: One paraffin-embedded tissue block from each case containing a sufficient amount of non-tumorous renal parenchyma was cut and processed with hematoxylin and eosin and periodic acid-Schiff methods. Non-neoplastic lesions of each histological compartment were semi-quantitatively and quantitatively evaluated. RESULTS: Among the various histologic lesions found, tubular atrophy, arterial intimal thickening, and glomerulosclerosis were the most common (94.1%, 91.8%, and 88.2%, respectively). Glomerulosclerosis correlated with estimated glomerular filtration rate at the time of surgery, as well as at 1- and 5-years post-surgery (p=.0071), but tubulointerstitial fibrosis or arterial fibrous intimal thickening did not. Post-hoc analysis revealed that glomerulosclerosis of more than 20% predicted post-operative renal function. However, its significance disappeared when gender and age were considered. CONCLUSIONS: In conclusion, non-neoplastic lesions, especially with regard to glomerulosclerosis percentage, should be described in pathology reports to provide additional information on renal function decline.