Low Serum Bicarbonate Predicts Residual Renal Function Loss in Peritoneal Dialysis Patients.

Low residual renal function (RRF) and serum bicarbonate are associated with adverse outcomes in peritoneal dialysis (PD) patients. However, a relationship between the 2 has not yet been determined in these patients. Therefore, this study aimed to investigate whether low serum bicarbonate has a deteriorating effect on RRF in PD patients.This prospective observational study included a total of 405 incident patients who started PD between January 2000 and December 2005. We determined risk factors for complete loss of RRF using competing risk methods and evaluated the effects of time-averaged serum bicarbonate (TA-Bic) on the decline of RRF over the first 3 years of dialysis treatment using generalized linear mixed models.During the first 3 years of dialysis, 95 (23.5%) patients became anuric. The mean time until patients became anuric was 20.8 ±â€Š9.0 months. After adjusting for multiple potentially confounding covariates, an increase in TA-Bic level was associated with a significantly decreased risk of loss of RRF (hazard ratio per 1 mEq/L increase, 0.84; 0.75-0.93; P = 0.002), and in comparison to TA-Bic ≥ 24 mEq/L, TA-Bic < 24 mEq/L conferred a 2.62-fold higher risk of becoming anuric. Furthermore, the rate of RRF decline estimated by generalized linear mixed models was significantly greater in patients with TA-Bic < 24 mEq/L compared with those with TA-Bic ≥ 24 mEq/L (-0.16 vs -0.11 mL/min/mo/1.73 m, P < 0.001).In this study, a clear association was found between low serum bicarbonate and loss of RRF in PD patients. Nevertheless, whether correction of metabolic acidosis for this indication provides additional protection for preserving RRF in these patients is unknown. Future interventional studies should more appropriately address this question.

Hyponatremia Predicts New-Onset Cardiovascular Events in Peritoneal Dialysis Patients.

BACKGROUND AND AIM: Cardiovascular (CV) disease is the leading cause of morbidity and mortality in patients on peritoneal dialysis (PD). Hyponatremia was recently shown to be a modifiable factor that is strongly associated with increased mortality in PD patients. However, the clinical impact of hyponatremia on CV outcomes in these patients is unclear. METHODS: To determine whether a low serum sodium level predicts the development of CV disease, we carried out a prospective observational study of 441 incident patients who started PD between January 2000 and December 2005. Time-averaged serum sodium (TA-Na) levels were determined to investigate the ability of hyponatremia to predict newly developed CV events in these patients. RESULTS: During a mean follow-up of 43.2 months, 106 (24.0%) patients developed new CV events. The cumulative incidence of new-onset CV events after the initiation of PD was significantly higher in patients with TA-Na levels ≤ 138 mEq/L than in those with a TA-Na > 138 mEq/L. After adjustment for multiple potentially confounding covariates, an increase in TA-Na level was found to be associated with a significantly lower risk of CV events (subdistribution hazard ratio per 1 mEq/L increase, 0.90; 95% confidence interval, 0.83-0.96; p = 0.003). Patients with a TA-Na ≤ 138 mEq/L had a 2.31-fold higher risk of suffering a CV event. CONCLUSIONS: These results provide evidence of a clear association between low serum sodium and new-onset CV events after dialysis initiation in PD patients. Whether the correction of hyponatremia for this indication provides additional protection for the development of CV disease in these patients remains to be addressed in interventional studies.

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.

Hyponatremia as a predictor of mortality in peritoneal dialysis patients.

BACKGROUND AND AIM: Hyponatremia is common in patients with chronic kidney disease and is associated with increased mortality in hemodialysis patients. However, few studies have addressed this issue in peritoneal dialysis (PD) patients. METHODS: This prospective observational study included a total of 441 incident patients who started PD between January 2000 and December 2005. Using time-averaged serum sodium (TA-Na) levels, we aimed to investigate whether hyponatremia can predict mortality in these patients. RESULTS: Among the baseline parameters, serum sodium level was positively associated with serum albumin (ß = 0.145; p = 0.003) and residual renal function (RRF) (ß = 0.130; p = 0.018) and inversely associated with PD ultrafiltration (ß = -0.114; p = 0.024) in a multivariable linear regression analysis. During a median follow-up of 34.8 months, 149 deaths were recorded. All-cause death occurred in 81 (55.9%) patients in the lowest tertile compared to 37 (25.0%) and 31 (20.9%) patients in the middle and highest tertiles, respectively. After adjusting for multiple potentially confounding covariates, increased TA-Na level was associated with a significantly decreased risk of all-cause (HR per 1 mEq/L increase, 0.79; 95% CI, 0.73-0.86; p<0.001) and infection-related (HR per 1 mEq/L increase, 0.77; 95% CI, 0.70-0.85; p<0.001) deaths. CONCLUSIONS: This study showed that hyponatremia is an independent predictor of mortality in PD patients. Nevertheless, whether correcting hyponatremia improves patient survival is unknown. Future interventional studies should address this question more appropriately.

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.

A low serum bicarbonate concentration as a risk factor for mortality in peritoneal dialysis patients.

BACKGROUND AND AIM: Metabolic acidosis is common in patients with chronic kidney disease and is associated with increased mortality in hemodialysis patients. However, this relationship has not yet been determined in peritoneal dialysis (PD) patients. METHODS: This prospective observational study included a total of 441 incident patients who started PD between January 2000 and December 2005. Using time-averaged serum bicarbonate (TA-Bic) levels, we aimed to investigate whether a low serum bicarbonate concentration can predict mortality in these patients. RESULTS: Among the baseline parameters, serum bicarbonate level was positively associated with hemoglobin level and residual glomerular filtration rate (GFR), while it was negatively associated with albumin, C-reactive protein (CRP) levels, peritoneal Kt/V urea, and normalized protein catabolic rate (nPCR) in a multivariable linear regression analysis. During a median follow-up of 34.8 months, 149 deaths were recorded. After adjustment for age, diabetes, coronary artery disease, serum albumin, ferritin, CRP, residual GFR, peritoneal Kt/V urea, nPCR, and percentage of lean body mass, TA-Bic level was associated with a significantly decreased risk of mortality (HR per 1 mEq/L increase, 0.83; 95% CI, 0.76-0.91; p < 0.001). In addition, compared to patients with a TA-Bic level of 24-26 mEq/L, those with a TA-Bic level < 22 and between 22-24 mEq/L conferred a 13.10- and 2.13-fold increased risk of death, respectively. CONCLUSIONS: This study showed that a low serum bicarbonate concentration is an independent risk factor for mortality in PD patients. This relationship between low bicarbonate levels and adverse outcome could be related to enhanced inflammation and a more rapid loss of RRF associated with metabolic acidosis. Large randomized clinical trials to correct acidosis are warranted to confirm our findings.

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.

Leptin/adiponectin ratio is an independent predictor of mortality in nondiabetic peritoneal dialysis patients.

BACKGROUND: The leptin/adiponectin (L/A) ratio has been suggested to be an atherosclerotic index for diabetic patients and a useful marker of insulin resistance in patients with and without diabetes. Even though end-stage renal disease (ESRD) patients on peritoneal dialysis (PD) are well characterized by abnormal adipocytokine metabolism, the significance of alterations in the L/A ratio is largely unexplored in these patients. In this prospective study, we investigated the associations of leptin, adiponectin, and the L/A ratio with clinical outcomes in nondiabetic PD patients. METHODS: The study included 131 stable nondiabetic ESRD patients who had been on PD for more than 3 months. Serum leptin and adiponectin levels were determined at baseline. Mortality was evaluated over a 5-year follow-up period. RESULTS: During the follow-up period, 22 patients died (16.8%), including 10 (45.5%) as a result of cardiovascular disease. The L/A ratio showed a significant positive correlation with body mass index [BMI (r = 0.47, p < 0.001)], high-sensitivity C-reactive protein (r = 0.32, p < 0.001), and triglycerides (r = 0.43, p < 0.001). In addition, we observed significant inverse correlations between the L/A ratio and percentage lean body mass (r = -0.30, p = 0.001) and high-density lipoprotein cholesterol (r = -0.31, p = 0.001). In contrast to individual leptin and adiponectin levels, the L/A ratio was found to be independently associated with an increased mortality risk (relative risk: 1.15; 95% confidence interval: 1.05 to 1.27; p = 0.003) even after adjustments for age and BMI. CONCLUSIONS: The L/A ratio might be better related to patient outcomes than adipocytokines are individually in nondiabetic patients undergoing PD.

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.

Low circulating adiponectin levels are associated with insulin resistance in non-obese peritoneal dialysis patients.

In patients with end-stage renal disease (ESRD), circulating adipokine levels are increased due to decreased renal clearance, irrespective of obesity. However, whether adipokines play a role in the development of insulin resistance (IR) in non-obese ESRD patients is unknown. We conducted a cross-sectional study to identify factors associated with IR in 62 non-obese patients on peritoneal dialysis (PD). Non-obesity was defined as body mass index (BMI) <25 kg/m(2). IR was determined using homeostatic model assessment-IR (HOMA-IR). We also measured serum concentrations of adiponectin, leptin, resistin, high-sensitivity C-reactive protein (hsCRP), and IL-6. The average BMI of the study patients was 21.6 kg/m(2). When patients were divided into two groups according to the median value of HOMA-IR, serum adiponectin levels were significantly lower in patients with HOMA-IR > 1.85 than in those with HOMA-IR ≤1.85, whereas serum concentrations of leptin and resistin did not differ between the two groups. In addition, log-transformed HOMA-IR was negatively correlated with adiponectin (γ = -0.464, P < 0.001) and log-transformed high-density lipoprotein cholesterol (γ = -0.250, P = 0.050) and positively correlated with age (γ = 0.334, P = 0.008) and triglyceride (γ = 0.392, P = 0.002). However, resistin, log-transformed leptin and log-transformed hsCRP were not associated with HOMA-IR. In a multiple linear regression model, adiponectin was independently associated with HOMA-IR (ß = -0.023, P = 0.015). In conclusion, this study suggests that low circulating adiponectin levels might be involved in IR even in non-obese patients undergoing PD.

Nutrition in patients on peritoneal dialysis.

Protein-energy wasting (PEW) is prevalent among patients on dialysis and has emerged as an important risk factor for morbidity and mortality in these patients. Numerous factors, including inflammation, inadequate dialysis, insufficient nutrient intake, loss of protein during dialysis, chronic acidosis, hypercatabolic illness and comorbid conditions, are involved in the development of PEW. The causes and clinical features of PEW in patients on peritoneal dialysis and hemodialysis are comparable; assessment of the factors that lead to PEW in patients receiving peritoneal dialysis is important to ensure that PEW is managed correctly in these patients. For the past 20 years, much progress has been made in the prevention and treatment of PEW. However, the results of most nutritional intervention studies are inconclusive. In addition, the multifactorial and complicated pathogenesis of PEW makes it difficult to assess and treat. This Review summarizes the nutritional issues regarding the causes, assessment and treatment of PEW, with a focus on patients receiving peritoneal dialysis. In addition, an in-depth overview of the results of nutritional intervention studies is provided.

Clinical features and outcomes of IgA nephropathy with nephrotic syndrome.

BACKGROUND AND OBJECTIVES: Nephrotic syndrome (NS) is a rare manifestation of IgA nephropathy (IgAN). Clinical characteristics and long-term outcomes of this condition have not yet been explored. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A multicenter observational study was conducted between January 2000 and September 2010 in 1076 patients with biopsy-proven IgAN from four medical centers in Korea. The primary outcome was a doubling of the baseline serum creatinine concentration. RESULTS: Of the 1076 patients, 100 (10.2%) presented with NS; complete remission (CR), partial remission (PR), and no response (NR) occurred in 48 (48%), 32 (32%), and 20 (20%) patients, respectively. During the median follow-up of 45.2 months, 24 patients (24%) in the NS group reached the primary endpoint compared with 63 (7.1%) in the non-NS group (P<0.001). The risk of reaching the primary endpoint was significantly higher in the PR (P=0.04) and NR groups (P<0.001) than in the CR group. Among patients with NS, 24 (24%) underwent spontaneous remission (SR). SR occurred more frequently in female patients and in patients with serum creatinine levels ≤1.2 mg/dl and a >50% decrease in proteinuria within 3 months after NS onset. None of the patients with SR reached the primary endpoint and they had fewer relapses during follow-up. CONCLUSIONS: This study demonstrated that the prognosis of NS in IgAN was not favorable unless PR or CR was achieved. In addition, SR was more common than expected, particularly in patients with preserved kidney function and spontaneous decrease in proteinuria shortly after NS onset.

Effects of icodextrin on patient survival and technique success in patients undergoing peritoneal dialysis.

BACKGROUND: Many studies have suggested clinical benefits of icodextrin in peritoneal dialysis (PD) patients regarding fluid management, glycaemic control and metabolic improvement. However, reports on whether icodextrin can improve patient and technique survival is sparse. METHODS: A total of 2163 patients from 54 centres in Korea who initiated PD from July 2003 to December 2006 were enrolled. Outcomes data were retrieved retrospectively from the Baxter Korea database. Among these patients, 641 patients who had been prescribed icodextrin for >50% of their PD duration were defined as the 'icodextrin' group and the remaining 1522 patients as the 'non-icodextrin' group. Propensity score matching yielded 640 matched pairs of patients. We compared all-cause mortality and technique failure rates between the two groups. RESULTS: There were no significant differences in age, gender, diabetes, cardiovascular comorbidity, socioeconomic status, biocompatible solution use in short dwells or centre experience between the two groups. Death occurred in 92 (14.4%) patients in the icodextrin group compared with 128 (20.0%) in the non-icodextrin group [hazard ratio (HR), 0.69; 95% confidence interval (CI), 0.53-0.90; P = 0.006]. In addition, icodextrin use was associated with a significantly lower risk of technique failure (HR, 0.60; 95% CI, 0.40-0.92; P = 0.018). The icodextrin group had fewer technique failures due to non-compliance compared with the non-icodextrin group whereas peritonitis- or ultrafiltration failure-related technique failure was not different between the two groups. CONCLUSION: This study further supports previous findings of long-term utilization of icodextrin solution improving patient and technique survival in PD patients. To confirm these results, a large randomized prospective study is warranted.

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% (ß = 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.

Combined vascular effects of HMG-CoA reductase inhibitor and angiotensin receptor blocker in non-diabetic patients undergoing peritoneal dialysis.

BACKGROUND: Statins and angiotensin receptor blockers (ARBs) are known to improve vascular dysfunction in patients with chronic kidney disease. However, these effects have been inconsistent in dialysis patients. Moreover, it is currently unknown whether adding statins to ARBs improves vascular dysfunction better than ARB monotherapy in these patients. METHODS: We conducted a prospective open randomized trial to investigate the effects of statin add-on to ARB on vascular protection in 124 nondiabetic patients undergoing peritoneal dialysis (PD). Initially, all patients received 80 mg/day of valsartan for 6 months. Excluding 10 patients who dropped out during this period, patients were randomly assigned to continue ARB treatment alone (n = 57) or to receive 10 mg/day of rosuvastatin (n = 57) added to ARB for the next 6 months. To assess vascular function, endothelium-dependent vasodilation and arterial stiffness were determined by brachial artery flow-mediated dilation (FMD) and brachial-ankle pulse wave velocity (baPWV), respectively. RESULTS: Compared to baseline values, ARB treatment for the first 6 months significantly improved FMD% (2.97 ± 2.64 to 3.57 ± 2.58 %, P < 0.001). In addition, there was a small but significant decrease in baPWV during this period (1691.5 ± 276.3 to 1635.0 ± 278.6 cm/s, P = 0.048). After randomization, add-on treatment further improved FMD% (3.57 ± 2.73 to 4.24 ± 2.77 %, P = 0.003), whereas ARB monotherapy did not (P = 0.02 for between-group difference). Further slight improvement in baPWV (1617.0 ± 280.9 to 1528.9 ± 266.8 cm/s, P = 0.021) was observed only in the combined treatment group (P = 0.28 for between-group difference). CONCLUSIONS: Adding a statin to the ARB was of some help in improving vascular dysfunction more effectively than ARB monotherapy in nondiabetic PD patients. However, whether such limited improvements can lead to better clinical outcomes requires further investigation.

Local kallikrein-kinin system is involved in podocyte apoptosis under diabetic conditions.

The kallikrein-kinin system (KKS) serves as the physiologic counterbalance to the renin-angiotensin system. This study was conducted to examine the changes in the expression of KKS components in podocytes under diabetic conditions and to elucidate the functional role of bradykinin (BK) in diabetes-associated podocyte apoptosis. Thirty-two rats were injected with either diluent (n = 16, C) or with streptozotocin intraperitoneally (n = 16, DM), and 8 rats from each group were treated with BK infusion for 6 weeks. Immortalized mouse podocytes were cultured in media containing 5.6 mmol/l glucose (NG), NG + 10(-7) mol/l AII (AII), or 30 mmol/l glucose (HG) with or without 10(-8) mol/l BK. Urinary albumin excretion was significantly higher in DM rats, and this increase was ameliorated by BK. Not only kininogen, kallikrein, and BK B1- and B2-receptor expression but also BK levels were significantly decreased in DM glomeruli and in cultured podocytes exposed to HG. The changes in the expressions of apoptosis-related molecules and the increase in the number of apoptotic cells in DM glomeruli as well as in HG- and AII-stimulated podocytes were significantly abrogated by BK. The suppressed KSS within podocytes under diabetic condition was associated with podocyte apoptosis, suggesting that BK may be beneficial in preventing podocyte loss in diabetic nephropathy.

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.

Insulin resistance and lower plasma adiponectin increase malignancy risk in nondiabetic continuous ambulatory peritoneal dialysis patients.

End-stage renal disease patients have a higher risk for developing cancer. Although several causes for this increased risk have been proposed, the risk factors for cancer development in this population have not been elucidated. The aim of this study was to determine whether metabolic derangements, including insulin resistance and altered adipokines, increase the risk of developing malignancies in peritoneal dialysis (PD) patients, who are vulnerable to metabolic disorders because of excessive glucose absorbed from the dialysate. Study subjects comprised 106 nondiabetic PD patients who had been on PD for a minimum of 3 months with no overt malignancy. Baseline anthropometry, fasting glucose, insulin, and adiponectin were measured. The development of malignancy was evaluated during the follow-up period. During the mean follow-up of 47.0 ± 23.7 months, malignancy occurred in 15 patients (14.2%). The most common site of cancer was the kidney (26.7%), followed by thyroid (13.3%) and stomach (13.3%). Baseline insulin levels and homeostasis model assessment of insulin resistance were significantly higher, whereas plasma adiponectin levels were significantly lower, in patients who developed malignancy. Cox proportional hazards analysis revealed that insulin levels, homeostasis model assessment of insulin resistance, and lower adiponectin were independent predictors of malignancy. These findings demonstrate that insulin resistance and lower adiponectin levels could be risk factors for malignancy in nondiabetic PD patients.

Spontaneous remission of IgA nephropathy associated with resolution of hepatitis A.

Although most cases of immunoglobulin A (IgA) nephropathy are idiopathic, several diseases are associated with IgA nephropathy. Of these, chronic liver disease resulting from hepatitis B or C virus infection has been reported as a secondary cause of IgA nephropathy. Recently, hepatitis A virus (HAV)-associated kidney disease has received attention because acute kidney injury can occur as a complication of HAV infection, generally caused by acute tubular necrosis or interstitial nephritis. However, unlike IgA nephropathy related to hepatitis B or C, HAV-associated IgA nephropathy is extremely rare and long-term outcomes have not been reported yet. We describe a case of spontaneous remission of IgA nephropathy associated with serologically documented HAV infection. The patient presented with microhematuria and moderate proteinuria, but acute kidney injury did not occur during active hepatic injury. Kidney biopsy specimens clearly showed mesangial IgA deposits with intact tubules and interstitium. Serum liver enzyme levels returned to reference values 1 month after the onset of acute hepatitis, but urinary protein excretion remained increased. Approximately 1 year later, urinary abnormalities were resolved and a second biopsy showed no mesangial IgA deposits. These findings suggest that IgA nephropathy can transiently accompany HAV infection, but may not progress to chronic glomerulonephritis after recovery from HAV.