Efficacy and cost-effectiveness of darbepoetin alfa once every 4 weeks versus continuous erythropoietin receptor activator once every 4 weeks for anemia correction in patients with chronic kidney disease not on dialysis.

BACKGROUND: For anemia management in patients with chronic kidney disease not on dialysis, darbepoetin alfa (DA), which has a shorter half-life but is more inexpensive than continuous erythropoietin receptor activator (CERA), is preferred in Korea. This study evaluated the efficacy, safety, and cost-effectiveness of once-in-4-weeks DA compared with once-in-4-weeks CERA in patients with chronic kidney disease not on dialysis. METHODS: In this randomized, prospective, non-inferiority study, 40 erythropoiesis-stimulating agent-naïve patients with chronic kidney disease not on dialysis were randomized 1:1 to the DA group and CERA group. They received the study drug once in 4 weeks during 10- or 12-week correction period and 24-week efficacy evaluation period. The primary outcomes were the mean difference in the changes in hemoglobin levels between baseline and efficacy evaluation period and hemoglobin response rates during the correction period. The secondary outcomes included differences in adverse events and costs. RESULTS: DA was non-inferior to CERA for anemia correction; the mean difference in the change in hemoglobin levels between the groups was -0.070 g/dL (95% confidence interval, -0.730 to 0.590 g/dL). Hemoglobin response rates were 100% with DA and 94.1% with CERA. Adverse events were comparable. The mean cost of DA was approximately one-third that of CERA (34,100 ± 7,600 Korean won/4 weeks vs. 115,500 ± 23,600 Korean won/4 weeks; p < 0.001). CONCLUSION: Once-in-4-weeks DA safely corrects anemia in erythropoiesis-stimulating agent-naïve patients with chronic kidney disease not on dialysis and is more cost-effective than once-in-4-weeks CERA.

Identification of a novel HLA-B allele, HLA-B*54:47, in a Korean individual.

B*54:47 allele differs from B*54:01:01:01 in codon 74 in exon 2.

Acute kidney injury in patients with acute-on-chronic liver failure: clinical significance and management.

Acute-on-chronic-liver failure (ACLF) refers to a phenomenon in which patients with chronic liver disease develop multiple organ failure due to acute exacerbation of underlying liver disease. More than 10 definitions of ACLF are extant around the world, and there is lack of consensus on whether extrahepatic organ failure is a main component or a consequence of ACLF. Asian and European consortiums have their own definitions of ACLF. The Asian Pacific Association for the Study of the Liver ACLF Research Consortium does not consider kidney failure as a diagnostic criterion for ACLF. Meanwhile, the European Association for the Study of the Liver Chronic Liver Failure and the North American Consortium for the Study of End-stage Liver Disease do consider kidney failure as an important factor in diagnosing and assessing the severity of ACLF. When kidney failure occurs in ACLF patients, treatment varies depending on the presence and stage of acute kidney injury (AKI). In general, the diagnosis of AKI in cirrhotic patients is based on the International Club of Ascites criteria: an increase of 0.3 mg/dL or more within 48 hours or a serum creatinine increase of 50% or more within one week. This study underscores the importance of kidney failure or AKI in patients with ACLF by reviewing its pathophysiology, prevention methods, and treatment approaches.

Prediction of Heart Function and Volume Status in End-Stage Kidney Disease Patients through N-Terminal Pro-Brain Natriuretic Peptide.

Background and Objectives: N-terminal pro-brain natriuretic peptide (NT-proBNP) is a biomarker used to predict heart failure and evaluate volume status in hemodialysis (HD) patients. However, it is difficult to determine the cutoff value for NT-proBNP in HD patients. In this study, we analyzed whether NT-proBNP helps predict heart function and volume status in HD patients. Materials and Methods: This prospective observational study enrolled 96 end-stage kidney disease patients with HD. All patients underwent echocardiography and bioimpedance spectroscopy (BIS) after an HD session. Overhydration (OH) was measured by BIS. Laboratory data were obtained preHD, while serum NT-proBNP was measured after HD. Interventions for blood pressure control and dry weight control were performed, and NT-proBNP was re-assessed after a month. Results: There was an inverse correlation between NT-proBNP and ejection fraction (EF) (ß = -0.34, p = 0.001). OH (ß = 0.331, p = 0.001) and diastolic dysfunction (ß = 0.226, p = 0.027) were associated with elevated NT-proBNP. In a subgroup analysis of diastolic dysfunction grade, NT-proBNP increased according to dysfunction grade (normal, 4177 pg/mL [2637-10,391]; grade 1, 9736 pg/mL [5471-21,110]; and grades 2-3, 26,237 pg/mL [16,975-49,465]). NT-proBNP showed a tendency toward a decrease in the 'reduced dry weight' group and toward an increase in the 'increased dry weight' group compared to the control group (ΔNT-proBNP, -210 pg/mL [-12,899 to 3142], p = 0.104; 1575 pg/mL [-113 to 6439], p = 0.118). Conclusions: We confirmed that NT-proBNP is associated with volume status as well as heart function in HD patients.

Minimal Change Disease Is Associated with Mitochondrial Injury and STING Pathway Activation.

We hypothesized that minimal change disease (MCD) pathogenesis may be associated with mitochondrial injury, and that the degree of mitochondrial injury at the time of diagnosis may serve as a valuable prognostic marker. We compared urinary mitochondrial DNA (mtDNA) at the time of diagnosis in patients with MCD and age- and sex-matched healthy controls (MHC) (n = 10 each). We analyzed the site and signal intensity of immunohistochemical (IHC) staining of stimulator of interferon genes (STING) using kidney tissues at the time of diagnosis in patients with MCD. Patients with MCD were divided into high (n = 6) and low-intensity (n = 14) subgroups according to the signal intensity. Urinary mtDNA levels were elevated in the MCD groups more than in the MHC group (p < 0.001). Time-averaged proteinuria and frequency of relapses during the follow-up period were higher in the high-intensity than in the low-intensity subgroup (1.18 ± 0.54 vs. 0.57 ± 0.45 g/day, p = 0.022; and 0.72 ± 0.60 vs. 0.09 ± 0.22 episodes/year, p = 0.022, respectively). Mitochondrial injury may be associated with MCD pathogenesis, and the signal intensity of STING IHC staining at the time of diagnosis could be used as a valuable prognostic marker in MCD.

Urinary C5b-9 as a Prognostic Marker in IgA Nephropathy.

C5b-9 plays an important role in the pathogenesis of immunoglobin A nephropathy (IgAN). We evaluated C5b-9 as a prognostic marker for IgAN. We prospectively enrolled 33 patients with biopsy-proven IgAN. We analyzed the correlation between baseline urinary C5b-9 levels, posttreatment changes in their levels, and clinical outcomes, including changes in proteinuria, estimated glomerular filtration rate (eGFR), and treatment response. Baseline urinary C5b-9 levels were positively correlated with proteinuria (r = 0.548, p = 0.001) at the time of diagnosis. Changes in urinary C5b-9 levels were positively correlated with changes in proteinuria (r = 0.644, p < 0.001) and inversely correlated with changes in eGFR (r = -0.410, p = 0.018) at 6 months after treatment. Changes in urinary C5b-9 levels were positively correlated with time-averaged proteinuria during the follow-up period (r = 0.461, p = 0.007) but were not correlated with the mean annual rate of eGFR decline (r = -0.282, p = 0.112). Baseline urinary C5b-9 levels were not a significant independent factor that could predict the treatment response in logistic regression analyses (odds ratio 0.997; 95% confidence interval, 0.993 to 1.000; p = 0.078). Currently, urinary C5b-9 is not a promising prognostic biomarker for IgAN, and further studies are needed.

Myostatin/Appendicular Skeletal Muscle Mass (ASM) Ratio, Not Myostatin, Is Associated with Low Handgrip Strength in Community-Dwelling Older Women.

BACKGROUND/AIMS: Elevated levels of serum myostatin have been proposed as a biomarker for sarcopenia. Recent studies have shown that elevated level of serum myostatin was associated with physical fitness and performance. This study aimed to examine the significance of myostatin in the association between muscle mass and physical performance in the elderly. METHODS: This cross-sectional study is based on the Korean Frailty and Aging Cohort study involving 1053 people aged 70 years or over. Anthropometric, physical performance, and laboratory data were collected. RESULTS: The mean age of the participants was 75.8 years, and 50.7% of them were female. Serum myostatin levels in men (3.7 ± 1.2 vs. 3.2 ± 1.1 ng/mL, p < 0.001) were higher compared with that in women. Serum myostatin level was associated with appendicular skeletal muscle mass (ASM) index and eGFR by cystatin C. Serum myostatin/ASM ratio was associated with handgrip strength in women. CONCLUSION: Higher serum myostatin levels were related with higher muscle mass and better physical performances in the elderly. Serum myostatin/ASM ratio may be a predictor for physical performance rather than myostatin.

Validation of an international prediction model including the Oxford classification in Korean patients with IgA nephropathy.

BACKGROUND: Recently, a new international risk prediction model including the Oxford classification was published which was validated in a large multi-ethnic cohort. Therefore, we aimed to validate this risk prediction model in Korean patients with IgA nephropathy. METHODS: This retrospective cohort study was conducted with 545 patients who diagnosed IgA nephropathy with renal biopsy in three medical centers. The primary outcome was defined as a reduction in estimated glomerular filtration rate (eGFR) of >50% or incident end-stage renal disease (ESRD). Continuous net reclassification improvement (cNRI) and integrated discrimination improvement (IDI) were used to validate models. RESULTS: During the median 3.6 years of follow-up period, 53 (9.7%) renal events occurred. In multivariable Cox regression model, M1 (hazard ratio [HR], 2.22; 95% confidence interval [CI], 1.02-4.82; p = .043), T1 (HR, 2.98; 95% CI, 1.39-6.39; p = .005) and T2 (HR, 4.80; 95% CI, 2.06-11.18; p < .001) lesions were associated with increased risk of renal outcome. When applied the international prediction model, the area under curve (AUC) for 5-year risk of renal outcome was 0.69, which was lower than previous validation and internally derived models. Moreover, cNRI and IDI analyses showed that discrimination and reclassification performance of the international model was inferior to the internally derived models. CONCLUSION: The international risk prediction model for IgA nephropathy showed not as good performance in Korean patients as previous validation in other ethnic group. Further validation of risk prediction model is needed for Korean patients with IgA nephropathy.

Minor Glomerular Abnormalities are Associated with Deterioration of Long-Term Kidney Function and Mitochondrial Injury.

Minor glomerular abnormalities (MGAs) are unclassified glomerular lesions indicated by the presence of minor structural abnormalities that are insufficient for a specific pathological diagnosis. The long-term clinical outcomes and pathogenesis have not been examined. We hypothesized that MGAs would be associated with the deterioration of long-term kidney function and increased urinary mitochondrial DNA (mtDNA) copy numbers. We retrospectively enrolled patients with MGAs, age-/sex-/estimated glomerular filtration rate (eGFR)-matched patients with immunoglobulin A nephropathy (IgAN), and similarly matched healthy controls (MHCs; n = 49 each). We analyzed the time × group interaction effects of the eGFR and compared mean annual eGFR decline rates between the groups. We prospectively enrolled patients with MGAs, age- and sex-matched patients with IgAN, and MHCs (n = 15 each) and compared their urinary mtDNA copy numbers. Compared to the MHC group, the MGA and IgAN groups displayed differences in the time × group effects of eGFR, higher mean annual rates of eGFR decline, and higher urinary mtDNA copy numbers; however, these groups did not significantly differ from each other. The results indicate that MGAs are associated with deteriorating long-term kidney function, and mitochondrial injury, despite few additional pathological changes. We suggest that clinicians conduct close long-term follow-up of patients with MGAs.

IgA nephropathy is associated with elevated urinary mitochondrial DNA copy numbers.

Mitochondrial injury plays important roles in the pathogenesis of various kidney diseases. However, mitochondrial injury in IgA nephropathy (IgAN) remains largely unexplored. Here, we examined the associations among mitochondrial injury, IgAN, and treatment outcomes. We prospectively enrolled patients with IgAN and age-/sex-matched healthy volunteers (HVs) as controls (n = 31 each). Urinary copy numbers of the mitochondrial DNA (mtDNA) genes cytochrome-c oxidase-3 (COX3) and nicotinamide adenine dinucleotide dehydrogenase subunit-1 (ND1) were measured. Urinary mtDNA levels were elevated in the IgAN group compared with that in HVs (p < 0.001). Urinary ND1 levels were significantly higher in the low proteinuria group than in the high proteinuria group (p = 0.027). Changes in urinary levels of ND1 and COX3 were positively correlated with changes in proteinuria (p = 0.038 and 0.024, respectively) and inversely correlated with changes in the estimated glomerular filtration rate (p = 0.033 and 0.017, respectively) after medical treatment. Mitochondrial injury played important roles in IgAN pathogenesis and may be involved in early-stage glomerular inflammation, prior to pathological changes and increased proteinuria. The correlation between changes in urinary mtDNA and proteinuria suggest that these factors may be promising biomarkers for treatment outcomes in IgAN.

Efficacy of low-dose spironolactone on top of angiotensin receptor blockade in patients with glomerulonephritis.

BACKGROUND: Previous studies have shown that aldosterone antagonists have a proteinuria-lowering effect in patients with proteinuria and progressive proteinuric disease not adequately controlled by the use of angiotensin receptor blockers (ARBs). Aldosterone antagonists, in combination with ARBs, might improve proteinuria in patients with glomerulonephritis (GN). METHODS: In the present retrospective study, we evaluated the proteinuria-lowering effect and drug safety of low-dose spironolactone (12.5 mg/day) in 42 patients with GN being treated with an ARB. RESULTS: Proteinuria decreased from a mean total-protein-to-creatinine (TP/Cr) ratio of 592.3 ± 42.0 mg/g at baseline to 335.6 ± 43.3 mg/g after three months of treatment with spironolactone (P < 0.001). After the initial three months, the mean TP/Cr ratio increased progressively at six, nine, and 12 months; however, it was still less than the baseline value (P = 0.001, < 0.001, and < 0.001, respectively). Although serum Cr levels increased significantly at three and nine months compared with baseline (P = 0.036 and 0.026, respectively), there was no time effect of treatment (P = 0.071). Serum potassium levels tended to increase with time (P = 0.118), whereas systolic and diastolic blood pressures decreased with time (P = 0.122 and 0.044, respectively). CONCLUSION: Low-dose spironolactone in combination with an ARB reduced proteinuria in patients with GN, which could represent a novel treatment option in individuals whose proteinuria is not optimally controlled by the use of ARBs alone.

The 24-Month Changes in Body Fat Mass and Adipokines in Patients Starting Peritoneal Dialysis.

♦ BACKGROUND: Peritoneal dialysis (PD) is characterized by a gain in fat mass. The fat tissue is a complex endocrine organ that releases various adipokines. In this study, we prospectively examined serial changes of fat composition and adipokines in patients undergoing PD. ♦ METHODS: Body composition was assessed by computed tomography (CT). Nutrition status and adipokines (leptin, adiponectin, interleukin [IL]-6, and tumor necrosis factor [TNF]-α) were assessed on the 7th day and 6 months, 12 months, and 24 months after the start of PD. ♦ RESULTS: Fifty-four patients (28 men), with a mean age of 53.2 ± 13.2 years, were enrolled. Baseline fat mass, especially subcutaneous fat mass, was correlated with baseline leptin (ρ = 0.612), adiponetin (ρ = -0.477), and interleukin-6 (IL-6) (ρ = 0.391). Visceral fat mass was correlated with leptin (ρ = 0.545) and adiponectin (ρ = -0.514). Baseline adiponectin was negatively correlated with baseline leptin (ρ = -0.363). While body weight and leptin increased during the 24 months, serum adiponectin decreased in that period. The changes in visceral and subcutaneous fat mass were greater in the first 12 months and 6 months, respectively. There was no difference in IL-6 and TNF-α. Eight patients died during the follow-up period (mean 47.4 months). Twenty-seven patients continued PD. Increased baseline and serial change of IL-6 level were risk factors for mortality. After adjusting for age, sex, diabetes mellitus (DM), and coronary vascular disease (CVD), the significance of the IL-6 level disappeared. ♦ CONCLUSIONS: Baseline subcutaneous fat in patients starting PD is correlated with baseline adipokine levels rather than visceral fat. The increase in subcutaneous fat was greatest in the first 6 months. While leptin and adiponectin increased and decreased respectively, IL-6 did not change in the first 24 months.

Clinical utility of far-infrared therapy for improvement of vascular access blood flow and pain control in hemodialysis patients.

BACKGROUND: Maintenance of a well-functioning vascular access and minimal needling pain are important goals for achieving adequate dialysis and improving the quality of life in hemodialysis (HD) patients. Far-infrared (FIR) therapy may improve endothelial function and increase access blood flow (Qa) and patency in HD patients. The aim of this study was to evaluate effects of FIR therapy on Qa and patency, and needling pain in HD patients. METHODS: This prospective clinical trial enrolled 25 outpatients who maintained HD with arteriovenous fistula. The other 25 patients were matched as control with age, sex, and diabetes. FIR therapy was administered for 40 minutes during HD 3 times/wk and continued for 12 months. The Qa was measured by the ultrasound dilution method, whereas pain was measured by a numeric rating scale at baseline, then once per month. RESULTS: One patient was transferred to another facility, and 7 patients stopped FIR therapy because of an increased body temperature and discomfort. FIR therapy improved the needling pain score from 4 to 2 after 1 year. FIR therapy increased the Qa by 3 months and maintained this change until 1 year, whereas control patients showed the decrease in Qa. The 1-year unassisted patency with FIR therapy was not significantly different from control. CONCLUSION: FIR therapy improved needling pain. Although FIR therapy improved Qa, the unassisted patency was not different compared with the control. A larger and multicenter study is needed to evaluate the effect of FIR therapy.

Biomarkers of kidney injury and klotho in patients with atherosclerotic renovascular disease.

BACKGROUND AND OBJECTIVES: Occlusive renovascular disease and hypertension may progress to CKD. Circulating levels of several biomarkers, including fibroblast growth factor (FGF)-23, Klotho, and soluble urokinase plasminogen activator receptor (suPAR), are altered in patients with CKD, but their role in essential hypertension (EH) and renovascular hypertension (RVH) remains unclear. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Levels of FGF-23, Klotho, suPAR, plasminogen activator inhibitor (PAI)-1, tissue factor, and tissue factor pathway inhibitor (TFI) were measured in the inferior vena cava and renal vein of hypertensive patients with atherosclerotic renal artery stenosis (n=12) or age-matched participants with EH (n=12) and relatively preserved renal function. Single-kidney blood flow was measured to calculate renal release of markers. For control, peripheral vein levels were measured in healthy volunteers (HVs; n=12). RESULTS: FGF-23 levels did not differ among the groups, whereas Klotho levels were lower in participants with RVH and EH than in HVs, and suPAR levels were elevated in patients with RVH compared with HVs and patients with EH (6.1±1.5 versus 4.4±1.9 and 3.2±1.2 ng/ml, P<0.05). PAI-1 levels were higher in patients with RVH than in patients with EH, but tissue factor and TFI levels were not statistically significantly different. After adjustment for GFR, Klotho levels remained decreased in both RVH and EH, and suPAR and PAI-1 levels remained elevated in RVH. eGFR correlated inversely with systemic and renal vein suPAR levels, and directly with systemic Klotho levels. CONCLUSIONS: Klotho levels are low in hypertensive patients, whereas suPAR and PAI-1 levels are specifically elevated in RVH, correlating with GFR. Klotho, PAI-1, and suPAR may be markers of kidney injury in hypertensive patients.

Circulating and renal vein levels of microRNAs in patients with renal artery stenosis.

BACKGROUND: MicroRNAs (miRs) are small non-coding RNAs that are important regulators of gene expression and have been implicated in atherosclerosis. Kidney injury distal to atherosclerotic renal artery stenosis (ARAS) is aggravated by atherosclerosis. Therefore, this study tested the hypothesis that renal miR expression would be altered in patients with ARAS. METHODS: Patients with essential hypertension (EH; n = 13) or ARAS (n = 13) underwent a 3-day protocol study under controlled conditions. For miR levels, blood samples were collected from EH and ARAS renal vein (RV) and inferior vena cava or peripheral vein of matched normotensive healthy volunteers (HV; n = 13) and patients with coronary atherosclerosis (CA; n = 11). Single-renal blood flow was measured in EH and ARAS using computer tomography to calculate renal gradients and release of miRs. RESULTS: Glomerular filtration rate (GFR) was lower in ARAS compared with the other groups. Systemic levels of most miRs were elevated in CA. RV miR levels were lower than systemic levels in both ARAS and EH. GFR-adjusted RV levels of miR-21, 155 and 210 were reduced only in ARAS patients compared with systemic levels in HV, although cross-kidney gradients were not different from EH. RV levels of miR-21, 126, 155 and 210 correlated with GFR. CONCLUSIONS: Levels of atherosclerosis-related miR-21, 126, 155 and 210 are decreased in the stenotic-kidney vein of ARAS compared with EH patients, likely due to decreased GFR. Yet, these miRs might be implicated in modulating renal injury in ARAS, and their RV level may be a marker reflecting their renal expression.

Could mean platelet volume be a promising biomarker of progression of chronic kidney disease?

The mean platelet volume (MPV), a readily available indicator of platelet activation and function, is a useful predictive and prognostic biomarker of cardiovascular and cerebrovascular disease (CVD). It is associated with a variety of prothrombotic and proinflammatory diseases. Larger platelets are more likely to aggregate and release greater quantities of adhesive molecules. MPV has seldom been investigated in patients with chronic kidney disease (CKD). This study aimed to investigate the relationship between MPV levels and the glomerular filtration rate (GFR) in patients with CKD. We reviewed the medical records of patients with CKD who visited the nephrology outpatient clinics of Soonchunhyang University Bucheon Hospital between January 2010 and May 2013. A total of 553 patients were included in the present retrospective study. According to the estimated GFR (eGFR) calculated by the abbreviated the Modification of Diet in Renal Disease (MDRD) equation, the patients were allocated to Group 1 (GFR, 60-89 ml/minute/1.73 m(2); n = 64), Group 2 (GFR, 30-59 ml/minute/1.73 m(2); n = 268), Group 3 (GFR, 15-29 ml/minute/1.73 m(2); n = 147), or Group 4 (GFR, <15 ml/minute/1.73 m(2) and non-dialysis; n = 74). Data were analyzed by Student's t-test, the chi-squared test, Pearson's correlation coefficient (r), Tukey's honestly significant difference (HSD) test, and one-way analysis of covariance. The MPV values had a negative correlation with eGFR in patients with CKD (Pearson's correlation coefficient = -0.553, p < 0.001). The mean MPV values in Groups 1-4 were 9.81 ± 0.13 fl, 10.34 ± 0.08 fl, 10.86 ± 0.09 fl, and 11.19 ± 0.11 fl, respectively (p < 0.001). Multiple comparisons of MPV values in the four groups by Tukey's HSD test showed statistically significant intergroup differences, with all p values <0.001. Platelet counts and PDW decreased along with eGFR, and there were no significant differences with respect to plateletcrit. Patients with prevalent coronary artery disease (CAD) or CVD had higher MPVs than did those without CAD or CVD. MPV was significantly increased with progression of CKD. MPV may be a useful indicator of increased risks of CAD or CVD in patients with CKD.

Ferritin as a predictor of decline in residual renal function in peritoneal dialysis patients.

AIMS: Inflammation is an important factor in renal injury. Ferritin, an inflammatory marker, is considered an independent predictor of rapid renal progression in patients with chronic kidney disease. However, the relationship between ferritin and residual renal function (RRF) in patients undergoing peritoneal dialysis (PD) remains unclear. METHODS: We reviewed the medical records of patients who started PD between June 2001 and March 2012 at Soonchunhyang University Bucheon Hospital, Korea. A total of 123 patients were enrolled in the study. At 1 month after the initiation of PD, RRF was determined by a 24-hour urine collection and measured every 6 months thereafter. Clinical and biochemical data at the time of the initial 24-hour urine collection were considered as baseline. RESULTS: The RRF reduction rate was significantly greater in patients with high ferritin (ferritin ≥ 250 ng/mL) compared with those with low ferritin (ferritin < 250 ng/mL; -1.71 ± 1.36 mL/min/yr/1.73 m(2) vs. -0.84 ± 1.63 mL/min/yr/1.73 m(2), respectively; p = 0.007). Pearson correlation analysis revealed a significant negative correlation between the baseline serum ferritin level and the RRF reduction rate (r = -0.219, p = 0.015). Using multiple linear regression analysis and adjusting for other risk factors, baseline serum ferritin was an independent factor for the RRF reduction rate (ß = -0.002, p = 0.002). CONCLUSIONS: In this study we showed that a higher ferritin level was significantly associated with a more rapid RRF decline in patients undergoing PD.

Does body fat mass define survival in patients starting peritoneal dialysis?

BACKGROUND AND AIMS: Peritoneal dialysis (PD) is characterized by a gain in fat mass. Unlike subcutaneous fat, visceral fat is associated with metabolic syndrome and survival. We prospectively examined whether visceral or subcutaneous fat could predict outcome in patients undergoing PD. METHODS: We studied 117 new patients (57 men) undergoing PD between February 2006 and November 2011. Baseline body composition was measured on computed tomograms. Visceral obesity was defined as a visceral fat area exceeding 100 cm(2), and subcutaneous obesity, as a subcutaneous fat area exceeding 130 cm(2). RESULTS: Among the 117 patients, 37 and 29 were diagnosed with visceral and subcutaneous obesity respectively. Visceral and subcutaneous obesity were both present in 21 patients. In the study population, the 1-year and 5-year survival rates were 94% and 59%. The rates of peritonitis and exit-infection were 0.31 and 0.14 episodes per patient-year. Mortality was greater in patients with visceral obesity than in those without visceral obesity (p = 0.005). Visceral obesity had no influence on peritonitis and exit-infection rates. Subcutaneous obesity was associated neither with survival nor with peritonitis or exit-site infection. In a multivariate Cox regression analysis, visceral obesity was not a risk factor for poor outcome. CONCLUSIONS: Increased visceral fat at PD initiation is not an independent predictor of poor survival. Any impact of visceral or subcutaneous fat mass on outcomes in patients undergoing PD would be better defined by larger, long-term studies.

Effect of treatment on urinary kidney injury molecule-1 in IgA nephropathy.

BACKGROUND: Kidney injury molecule-1 (KIM-1) is a biomarker useful for detecting early tubular damage and has been recently reported as a useful marker for evaluating kidney injury in IgA nephropathy (IgAN). We therefore investigated whether treatment decreases urinary KIM-1 excretion in IgAN. METHODS: We prospectively enrolled 37 patients with biopsy-proven IgAN. Urinary KIM-1 was assessed before and after treatment, which included low salt diet, blood pressure control, pharmacotherapy with angiotensin receptor blockers and/or angiotensin converting enzyme inhibitors, and immunosuppressive agents as necessary. The median treatment duration was 24 months. RESULTS: Urinary KIM-1/creatinine (Cr) was significantly decreased in patients with IgAN after treatment compared to baseline (P < 0.0001, 1.16 [0.51-1.83] vs 0.26 [0.12-0.65] ng/mg). There was a decrease in the amount of proteinuria after treatment, but it was not statistically significant (P = 0.052, 748.1 [405-1569.7] vs 569.2 [252.2-1114] g/d). Estimated glomerular filtration rate (eGFR) did not change with treatment (P = 0.599, 79.28 ± 30.56 vs 80.98 ± 32.37 ml/min/1.73 m2). Urinary KIM-1 was not correlated with proteinuria baseline or follow up (pre-: R = - 0.100, P = 0.577, post-: R = 0.001, P = 0.993). In patients with higher baseline urinary KIM-1, both urinary KIM-1 level and proteinuria were significantly decreased following treatment. CONCLUSIONS: Treatment decreases urinary KIM-1/Cr in patients with IgAN. It also reduces proteinuria in patients with higher baseline urinary KIM-1. These results suggest a potential role for urinary KIM-1 as a biomarker for predicting treatment response in IgAN, however, further study is needed to verify this.