New insight of amino acid-based dialysis solutions

Malnutrition is a major complication of peritoneal dialysis (PD) and is associated with increased morbidity and mortality. Daily losses of proteins and amino acids (AAs) into dialysate contribute to this problem. Previous metabolic balance study demonstrated that treatment with 1.1% AA-based dialysis solution is safe and may improve protein malnutrition in continuous ambulatory peritoneal dialysis (CAPD) patients ingesting low protein intake. Other prospective studies also showed that AA solution can provide nutritional benefit for malnourished PD patients resulting in a significant improvement in some biochemical and/or anthropometric nutritional parameters. However, there are other studies showing no particular improvement in nutritional parameters after long-term use of AA solution. This may be related to the differences in the study design, sample size, methods used to assess nutritional status, and other factors such as dietary intake and comorbidities of study subjects. Published data will be reviewed to further emphasize the nutritional benefit of long-term use of AA solution in malnourished PD patients along with a brief discussion on the various reasons that may partly explain the different study results. We will also present the results of a longitudinal observational study evaluating changes in nutritional parameters following use of one exchange of 1.1% AA solution in malnourished Korean PD patients. A significant improvement of somatic protein status such as lean body mass (LBM) and hand grip strength was observed. No significant change in serum albumin level was noted. Patients with a positive estimated coefficient for LBM in the fitted regression model to the repeated observations over 1 year were classified as responders and patients with neutral or negative coefficient were considered as non-responders. Thirty-one out of 43 malnourished patients (72%) showed nutritional benefit based on the change of LBM. Hand grip strength and back lift strength were significantly higher in responders at baseline. Other baseline parameters did not differ between the two groups.ope

Differential Expression of Nephrin According to Glomerular Size in Early Diabetic Kidney Disease

Diabetic nephropathy (DN) is clinically characterized by proteinuria. Many studies tried to demonstrate a relationship between proteinuria and changes in nephrin in various forms of glomerular diseases including DN, but the results are not consistent. Glomerular hypertrophy occurs in DN, yet hypertrophy does not develop in all glomeruli concurrently. For investigation of the differences in nephrin expression according to glomerular size, glomeruli were isolated from 10 control and 10 streptozotocin-induced diabetic rats at 6 wk after the induction of diabetes by a sieving technique using sieves with pore sizes of 250, 150, 125, and 75 microm. Glomeruli then were classified into large glomeruli (LG; on the 125-microm sieve) and small glomeruli (SG; on the 75-microm sieve) groups. Glomerular volumes were determined using an image analyzer, and mRNA and protein expression was determined by real-time PCR and Western blot, respectively. The mean volumes of diabetic LG (1.51 +/- 0.06 x 10(6) microm(3)) and control LG (1.37 +/- 0.05 x 10(6) microm(3)) were significantly higher than those of diabetic SG (0.94 +/- 0.03 x 10(6) microm(3)) and control SG (0.87 +/- 0.03 x 10(6) microm(3); P < 0.01). Nephrin mRNA expression was significantly reduced in the diabetic LG group compared with the diabetic SG and control glomeruli groups (P < 0.05). In contrast, nephrin mRNA expression was significantly higher in the diabetic SG group compared with the diabetic LG and control glomeruli groups (P < 0.05). Even after correction for 18s rRNA and Wilms' tumor-1 mRNA expression, the differences in nephrin mRNA expression remained significant. The expression of nephrin protein showed a similar pattern to the mRNA expression. In conclusion, these data suggest that the nephrin gene is differentially expressed according to glomerular size. Furthermore, more hypertrophied glomeruli with lesser nephrin expression may be responsible for albuminuria in the early stage of DN.ope

Serial Changes of QT Dispersion in Continuous Ambulatory Peritoneal Dialysis Patients

Purpose: To evaluate the changes of QT dispersion (QTd) in CAPD patients serially from the period before the initiation of CAPD until several years after CAPD, and to find any associated factors. Methods: We performed a retrospective cohort study with a total of 101 patients who initiated CAPD between 1990 and 1996. All data were recruited from the patients` medical records before CAPD initiation, within one year after CAPD, and between one and three years after CAPD. Results: QTd and Corrected QTd (QTdc) values after CAPD did not show differences in the paired t-test of those before CAPD and within one year after CAPD. There was a definite correlation between the QTds before CAPD and that within one year after CAPD (r=0.530, p<0.001). In addition, the QTds from within one year after CAPD showed a correlation with those taken from one to three years after CAPD (r=0.487, p=0.019). Upon analysis of all-cause mortality, the change rate of QTd after CAPD initiation was revealed as a predicting factor along with the QTd, QTc max, and QTdc within one year after CAPD (RR=1.055, p=0.005). The change rate also remained a predictor of cardiovascular mortality (RR=1.088, p=0.007). In a multivariate Cox regression, cardiomegaly and previous cardiovascular disease were revealed to be independent factors for the change rate of QTd. Conclusion: QTd in CAPD patients did not change after initiation of CAPD, and the change rate of QTd after CAPD initiation was revealed as a risk factor for both all-cause mortality and cardiovascular mortality.ope

Spontaneous remission of nephrotic syndrome in patients with IgA nephropathy.

BACKGROUND: IgA nephropathy (IgAN) can be complicated by nephrotic syndrome. Because the spontaneous resolution of heavy proteinuria is rare, corticosteroid therapy should be considered in such cases, particularly when IgAN is combined with minimal-change disease. Here, we report our experience of spontaneous remission of nephrotic syndrome in patients with IgAN and the long-term outcomes of these patients. METHODS: Two hundred and thirty-three patients with biopsy-proven IgAN were enrolled between January 2001 and March 2009. Demographic, clinical and laboratory data were collected retrospectively based on medical records. In addition, pathologic findings were reviewed for glomerular and tubulointerstitial lesions. Outcome data for complete or partial remission, spontaneous remission, relapse, deterioration of renal function, and end-stage renal disease were recorded. RESULTS: Twenty-four patients (10.3%) presented nephrotic syndrome. Among them, five patients underwent spontaneous remission within 6 months after the presentation of nephrotic syndrome. Interestingly, spontaneous remission occurred even in two patients who had elevated serum creatinine levels and advanced renal damage. During follow-up, neither recurrence nor relapse occurred, and no patients showed progressive deterioration of kidney function. Conclusions. This study suggests that spontaneous remission of nephrotic syndrome may occur in any stage of IgAN and carries a favourable long-term outcome without relapse. Given the possibility of under-reported cases, large-scale studies are required, and careful attention should be paid to such complicated cases.ope

A case of IgA nephropathy with systemic lupus erythematosus

In systemic lupus erythematosus patients, prevalence of renal involvement is high, even in the absence of overt clinical manifestation. Lupus nephritis can usually be categorized according to the widely used WHO classification. however, clinically significant renal disease unrelated to lupus nephritis have rarely been described in patients with SLE. Especially, there has been few reported cases of IgA nephropathy with SLE since first reported in 1995, but their relationship is not apparent yet. We experienced a 72-year-old female who was admitted to our hospital due to generalized ederrla, arthralgia, proteinuna, microscopic hematuria. Her diagnosis of IgA nephropathy was estabilished on biopsy. At the same time, she was diagnosed as SLE. in that the serology for ANA was positive at 1640, lupus anticoagulant and anti-cardiolipin antibody were positive, hemolytic anemia, arthritis and oral ulcer. and eventually she was diagnosed end-stage renal disease 2 months later. In conclusion, atypical glomerular lesion in SLE should raise the possibility of a non-lupus glomerulopathy, including IgA nephropathyope

Differences in Pathologic Findings and Gene Expressions of Renal Tissue according to Steroid Responsiveness in Adult-Onset Minimal Change Disease

Purpose: Compared to children, adult MCD patients tend to have a slower response to steroids, however, little is known about the relationships between pathologic findings or the expression of certain gene and the response to steroid treatment in adult-onset MCD. This study was undertaken to investigate the differences in pathologic findings and the mRNA expression of nephrin and glucocorticoid receptor (GCR) in renal tissue according to steroid responsiveness in adult-onset MCD. Methods: Twenty-eight adult patients who presented with idiopathic nephrotic syndrome at our institution and fulfilled the criteria for MCD clinically and pathologically were chosen for this study. Based on the response to steroid treatment, patients were divided into two groups: early responders (ER) in whom CR was achieved within 4 weeks of steroid treatment; late responders (LR) in whom CR was achieved after 4 weeks of steroid treatment. Results: Of the 28 patients, ER consisted of 20 patients. Time to CR was significantly shorter in ER compared to LR (16.5±0.9 vs. 52.0±4.9 days, p<0.01). The proportion of patients with minimal IgM deposition on immunofluorescence was significantly higher in LR compared to ER (75.0% vs. 30.0%, p<0.01). On the other hands, the mRNA expression of GCR, assessed by real time-PCR, was significantly lower in LR than that in ER (p<0.005), whereas nephrin mRNA expression was not different between the two groups. Conclusion: The presence of glomerular IgM deposition and the amount of GCR in renal tissue may be useful predictors of steroid responsiveness in adult MCD patients.ope

Activation of local aldosterone system within podocytes is involved in apoptosis under diabetic conditions

Previous studies have shown that mineralocorticoid receptor (MCR) blocker reduces proteinuria in diabetic nephropathy (DN), but the role of aldosterone in podocyte injury has never been explored in DN. This study was undertaken to elucidate whether a local aldosterone system existed in podocytes and to examine its role in podocyte apoptosis under diabetic conditions. In vitro, immortalized podocytes were exposed to 5.6 mM glucose (NG), NG + 24.4 mM mannitol, and 30 mM glucose (HG) with or without 10(-7) M spironolactone (SPR). In vivo, 32 Sprague-Dawley rats were injected with diluent (C, n = 16) or streptozotocin intraperitoneally [diabetes mellitus (DM), n = 16], and 8 rats from each group were treated with SPR for 3 mo. Aldosterone synthase (CYP11B2) and MCR mRNA and protein expression were determined by real-time PCR and Western blot, respectively, and aldosterone levels by radioimmunoassay. Western blot for apoptosis-related molecules, Hoechst 33342 staining, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay were performed to determine apoptosis. CYP11B2 and MCR expression were significantly higher in HG-stimulated podocytes and DM glomeruli compared with NG cells and C glomeruli, respectively, along with increased aldosterone levels. Western blot analysis revealed that cleaved caspase-3 and Bax expression was significantly increased, whereas Bcl-2 expression was significantly decreased in HG-stimulated podocytes and in DM glomeruli. Apoptosis determined by Hoechst 33342 staining and TUNEL assay were also significantly increased in podocytes under diabetic conditions. These changes in the expression of apoptosis-related proteins and the increase in apoptotic cells were inhibited by SPR treatment. These findings suggest that a local aldosterone system is activated and is involved in podocyte apoptosis under diabetic conditions.ope

Prognostic value of elevated cardiac troponin I in ESRD patients with sepsis

BACKGROUND: Elevated cardiac troponin (cTn) levels have been reported to predict adverse cardiovascular outcomes in asymptomatic ESRD patients. However, the prognostic value of elevated cTn levels associated with sepsis in ESRD patients is unknown. Therefore, this study aimed to elucidate the clinical implications of elevated cTnI levels in ESRD patients with sepsis. METHODS: Of the 305 ESRD patients in whom cTnI was measured between January 2003 and December 2005, sepsis developed in 121 patients during follow-up. Based on cTnI levels at the onset of sepsis, patients were classified as elevated cTnI group (ET, n = 50, >0.2 ng/ml) and lower cTnI group (LT, n = 71, < or =0.2 ng/ml). Study endpoints were short- and long-term mortality. Short-term mortality was defined as death occurring within 90 days after sepsis, and patients who survived during this period were followed till death after 90 days. RESULTS: Before sepsis, the median concentration of cTnI was 0.05 (0.01-3.59) ng/ml and it was significantly increased to 0.11 (0.01-22.0) ng/ml when sepsis supervened (P < 0.01). Compared to the LT group, the short-term mortality rate was significantly higher in the ET group (P < 0.05). After adjustment for age, diabetes, serum albumin and CRP levels, presence of shock and previous cardiovascular disease history, the ET group had a greater odds ratio of short-term mortality (OR 5.13, P < 0.01). In addition, the Kaplan-Meier plot for long-term survival revealed a significantly higher mortality rate in the ET group. In a multivariate Cox regression analysis, the elevation of cTnI levels was an independent determinant for long-term mortality (HR 5.90, P < 0.01). CONCLUSION: This study showed that elevated cTnI levels were significantly associated with short- and long-term mortality in ESRD patients with sepsis. Therefore, elevated cTnI levels in these patients should not be overlooked and be followed for adverse outcomes.ope

Reduced residual renal function is associated with endothelial dysfunction in patients receiving peritoneal dialysis

BACKGROUND: Endothelial dysfunction, which contributes to atherosclerosis and arteriosclerosis, commonly accompanies end-stage renal disease (ESRD). However, little is known about the role of residual renal function (RRF) in endothelial protection in ESRD patients. This study aimed to investigate the relationship between endothelial function and RRF in patients undergoing peritoneal dialysis (PD). METHODS: This was a cross-sectional study involving 72 prevalent PD patients. Demographic and clinical data were recorded and residual glomerular filtration rate (GFR), Kt/V urea, and serum concentrations of inflammatory markers were measured. Endothelial function was assessed by brachial artery endothelium-dependent vasodilation [flow-mediated dilation (FMD)] to reactive hyperemia following 5 minutes of forearm ischemia. RESULTS: In patients with FMD% above the median value (FMD > 2.41%), residual GFR was significantly higher compared to that in patients with FMD% below the median [1.50 (0 - 9.64) vs 0.48 (0 - 3.89) mL/min/1.73 m(2), P = 0.026]. Correlation analyses revealed that residual GFR (ρ = 0.381, P = 0.001) and total Kt/V urea (γ = 0.408, P < 0.001) were positively correlated with FMD%, whereas PD duration (γ = -0.351, P = 0.003), high-sensitivity C-reactive protein (ρ = -0.345, P = 0.003), pulse pressure (γ = -0.341, P = 0.003), and age (γ = -0.403, P < 0.001) were inversely correlated with FMD%. In contrast, there was no correlation between peritoneal Kt/V urea and FMD%. In multivariate linear regression analysis adjusted for these factors, residual GFR was found to be an independent determinant of FMD% (β = 0.317, P = 0.017). CONCLUSION: This study shows that RRF is independently associated with endothelial dysfunction in ESRD patients on PD, suggesting that RRF may contribute to endothelial protection in these patients.ope

Serum Adiponectin as a Predictor for Cardiovascular Outcomes in Non-Diabetic End-Stage Renal Disease Patients

Purpose: Adiponectin (ADPN) has been known to protect against cardiovascular disease (CVD) in metabolic syndrome with normal renal function for its anti-inflammatory and anti-atherogenic property. However, it is still unclear whether ADPN is associated with cardiovascular outcomes in end-stage renal disease (ESRD) patients. Methods: This study included 80 non-diabetic ESRD patients [mean age, 52.8±13.7 years; dialysis duration, 67.1±52.0 months; hemodialysis (HD), 35 pts; peritoneal dialysis (PD), 45 pts] who survived for more than 3 months after the start of dialysis, and serum ADPN levels were measured at the beginning of the study. We conducted a longitudinal follow-up to evaluate the association of serum ADPN level with cardiovascular outcomes for 29.3±6.7 months. Results: ADPN was inversely correlated with fasting serum insulin (r=-0.309, p=0.006) and HOMA-IR (r=-0.321, p=0.004) in ESRD patients. In a multiple linear regression analysis adjusted for age, gender, waist to hip ratio (WHR), and HDL-cholesterol, HOMA-IR (β=-0.880, p=0.041) was an independent factor associated with serum ADPN level. Kaplan-Meier analysis revealed that patients with higher ADPN levels (≥15.8 μg/mL) had a significantly higher survival rate compared with lowers (<15.8 μg/ mL) (p=0.032). Cox proportional hazard model adjusted for age, WHR, creatinine, CRP, and previous CVD history revealed that serum ADPN level (HR, 0.899; 95% CI, 0.818-0.987; p=0.026) was an independent determinant of cardiovascular outcomes. Conclusion: These findings suggest that lower ADPN levels independently predict cardiovascular events in non-diabetic ESRD patients.ope