Renoprotective efficacy of valsartan in chronic non-diabetic proteinuric nephropathies with renin-angiotensin system gene polymorphisms.

AIM: The renoprotective effects of angiotensin receptor blockers vary considerably among individuals. We investigated the renoprotective effects of valsartan according to polymorphisms of the renin-angiotensin system and transforming growth factor-b1 (TGFB1) genes in patients with chronic non-diabetic proteinuric nephropathies. METHODS: Two hundred and thirty-nine non-diabetic patients with proteinuria of at least 1 g/day were enrolled. Patients received 80 g of valsartan daily, followed by 160 mg/day after 6 weeks. The follow-up period was 18 months. The status of the angiotensin-converting enzyme (ACE) insertion/deletion, angiotensinogen (AGT) M235T, type 1 angiotensin II receptor (ATR1) A1166C, and TGFB1 C509 and T869C polymorphisms was determined in 162 patients. RESULTS: Valsartan treatment caused a significant reduction in proteinuria from baseline throughout the study in patients with each genotype of the ACE, AGT and TGFB1 genes. However, patients with the ATR1 AC genotype had no significant reduction in proteinuria from baseline throughout the study course. The median reductions in proteinuria after 6 months were 45.7% and 10.8% in the patients with the ATR1 AA and AC genotypes, respectively (P = 0.034). The annual change in the estimated glomerular filtration rate did not differ significantly among the genotypes for each gene. On multiple regression analysis, the change in proteinuria after 6 months of treatment was independently associated with the ATR1 genotype and the change in blood pressure (P = 0.005 and 0.019, respectively). CONCLUSION: Valsartan treatment significantly reduced the blood pressure and urinary protein excretion of patients with chronic non-diabetic proteinuric nephropathies. Interindividual differences in the anti-proteinuric effect of valsartan may be related partly to the ATR1 A1166C polymorphism.

Risk factors for consequent kidney impairment and differential impact of liver transplantation on renal function.

BACKGROUND: Chronic kidney disease (CKD) develops frequently after liver transplantation (LTx), and it is important to identify and correct risk factors that negatively affect kidney function. Risk factors have not been well evaluated in Asian countries where hepatitis B virus (HBV) infection is a dominant cause. METHODS: Four hundred thirty-one Korean recipients who underwent LTx between 1997 and 2008 were analysed. CKD was defined as a sustained decrease in estimated glomerular filtration rate (eGFR) of <60 (mL/min/1.73 m(2)) for at least three consecutive months using an abbreviated Modification in Renal Disease (MDRD) formula. RESULTS: Eighty percent of the patients had HBV-related underlying diseases. The recipients whose pretransplant eGFR had been low (<30 mL/min/1.73 m(2)) improved their renal function after LTx, but significant functional decline occurred in recipients whose pretransplant eGFR was high (>or=60 mL/min/1.73 m(2)). A multivariate Cox regression analysis revealed that the overall risk of CKD development (eGFR < 60 mL/min/1.73 m(2)) was associated with old age of recipients, cyclosporine, posttransplant acute renal failure (ARF), cause [calcineurin inhibitor (CNI) nephrotoxicity] and severity of posttransplant ARF, low pretransplant eGFR, pretransplant hepatorenal syndrome, pretransplant proteinuria, high Child-Pugh score and high Model for End-Stage Renal Disease (MELD) score. Especially in recipients whose pre-operative eGFR was high (>or=60 mL/min/1.73 m(2)), rapid progression of kidney disease was associated with high tacrolimus level, non-HBV disease, posttransplant ARF, cause (CNI nephrotoxicity) and severity of posttransplant ARF and Child-Pugh score. CNI toxicity and focal segmental sclerosis, but not immune-complex disease, were revealed as significant contributors to CKD after LTx in HBV recipients. CONCLUSION: Judicious use of CNIs should be applied to liver recipients to prevent kidney dysfunction.

Baseline peritoneal solute transport rate is not associated with markers of systemic inflammation or comorbidity in incident Korean peritoneal dialysis patients.

BACKGROUND: It is controversial whether comorbid status or systemic inflammation has an influence on the peritoneal solute transport rate (PSTR). Our aim is to elucidate whether baseline PSTR is associated with markers of systemic inflammation or degree of comorbidity in incident peritoneal dialysis (PD) patients. METHODS: One hundred and ninety-five incident PD patients were prospectively included. Results of their baseline peritoneal equilibration test (PET) using 3.86% glucose PD fluid were analysed. Clinical and laboratory parameters of inflammation, comorbidity, nutritional status, dialysis adequacy and residual renal function (RRF) were assessed at the time of PET. RESULTS: Mean dialysate-to-plasma ratio for creatinine at 4 h (D/Pcr(4)) of our patients was 0.72 +/- 0.11. High-sensitivity C-reactive protein (hsCRP), serum interleukin-6 (IL-6) and serum albumin concentrations were closely interrelated to one another and these markers of systemic inflammation were also related to the Davies comorbidity score. No differences in age, sex ratio, body mass index, body surface area and presence of diabetes were found among four transport groups. RRF, total Kt/V, haemoglobin, nitrogen appearance and the Davies comorbidity score were not different either. High-sensitivity CRP, serum IL-6 and albumin concentrations were not associated with the baseline PSTR. By multiple linear regression analysis, only the serum albumin concentration measured at the time of PET (beta = -0.081 +/- 0.020, P < 0.001) remained significantly associated with D/Pcr(4). CONCLUSION: In our study with incident Korean PD patients, the baseline PSTR was not influenced by markers of systemic inflammation or comorbidity. For a subgroup of PD patients without serious comorbidity, other mechanisms of high baseline PSTR need to be elucidated.

Treatment of depression and effect of antidepression treatment on nutritional status in chronic hemodialysis patients.

BACKGROUND: Depression, which is the most common psychological complication in patients with end-stage renal disease (ESRD), has an impact on the clinical outcome and is associated with malnutrition in chronic hemodialysis patients. This study evaluated the effect of antidepression treatment on nutritional status in depressed chronic hemodialysis patients. METHODS: Sixty-two ESRD patients who underwent dialysis for more than 6 months were interviewed and completed a Beck Depression Inventory assessment. Thirty-four patients who had scores greater than 18 on the Beck Depression Inventory score and met Diagnostic and Statistical Manual of Mental Disorders, 4th Edition criteria for major depressive disorder were selected to receive paroxetine 10 mg/day and psychotherapy for 8 weeks. The remaining 28 patients were assigned to the control group. Change in the severity of depressive symptoms was ascertained by administering the Hamilton Depression Rating Scale. Nutritional status was evaluated by normalized protein catabolic rate, serum albumin and blood urea nitrogen level. RESULTS: All patients successfully completed 8 weeks of antidepression treatment. Antidepression treatment decreased the severity of depressive symptoms (Hamilton Depression Rating Scale score: 16.6 +/- 7.0 versus 15.1 +/- 6.6, P < 0.01) and increased normalized protein catabolic rate (1.04 +/- 0.24 versus 1.17 +/- 0.29 g/kg/day, P < 0.05), serum albumin (37.3 +/- 2.0 versus 38.7 +/- 3.2 g/l, P < 0.005), and prehemodialysis blood urea nitrogen level (24.3 +/- 5.6 versus 30.2 +/- 7.9 mmol/L, P < 0.001). In the control group, no change was noted during the study period. CONCLUSION: This study suggests that antidepressant medication with supportive psychotherapy can successfully treat depression and improve nutritional status in chronic hemodialysis patients with depression.

Association of depression with malnutrition in chronic hemodialysis patients.

BACKGROUND: Depression is the most common psychological complication and may increase mortality in chronic hemodialysis patients. Because depression could be associated with poor oral intake and activation of proinflammatory cytokines that could further increase mortality by malnutrition, we investigated the relation between depression and nutritional status in chronic hemodialysis patients. METHODS: Sixty-two Korean patients completed the Beck Depression Inventory (BDI) questionnaire, and the diagnosis of depression was confirmed by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for major depressive disorder. Nutritional status was evaluated using serum albumin level, normalized protein catabolic rate, subjective global assessment (SGA), and anthropometric measurement. RESULTS: Mean BDI score was 22.7 +/- 11.4, and 35 patients (56.5%) had a BDI score greater than 21, which is the suggested cutoff score for the diagnosis of depression for the Korean population. Of 40 patients who had a score higher than 18 on the BDI, 34 patients met DSM-IV criteria for major depressive disorder. BDI score correlated negatively with a variety of nutritional parameters: serum albumin level (r = -0.47; P < 0.001), normalized protein catabolic rate (r = -0.32; P < 0.05), SGA (r = -0.47; P < 0.01), triceps skinfold thickness (r = -0.40; P < 0.05), midarm muscle circumference (r = -0.57; P < 0.01), and body mass index (r = -0.28; P < 0.05). Multiple regression analysis also identified BDI score as an independent determinant for all kinds of nutritional parameters. CONCLUSION: In patients on chronic hemodialysis therapy, depression is related closely to nutritional status and could be an independent risk factor for malnutrition.

KLOTHO gene polymorphism is associated with coronary artery stenosis but not with coronary calcification in a Korean population.

Experimental studies have demonstrated KLOTHO gene polymorphism might be associated with vascular atherosclerosis and calcification. However, the impact of this genetic variant on human coronary arteries still remains to be elucidated. We investigated the effect of a KLOTHO gene variant on coronary artery stenosis and calcification. Four hundred and thirty-four patients referred for chest pain were enrolled. All the patients underwent coronary angiography and were investigated for polymorphism of the KLOTHO G395A gene. Coronary artery disease (CAD) was defined as > or = 50% diameter stenosis in at least one coronary artery. The other patients were considered to be controls. Homozygotes or heterozygotes for G395A were significantly more common in the CAD patients than in the controls (30.2% versus 21.5%, P = 0.039). In the subgroup aged < 60 years, the G395A mutant was more frequent in CAD than in control (35.3% versus 18.8%, P = 0.016), but in patients > or = 60 years, there was no difference (28.0% versus 24.1%, P = 0.473). Using multivariate analysis, we identified the KLOTHO gene G395A mutant as an independent risk factor of CAD (OR 1.712, 95% CI [1.066-2.749], P = 0.026). The frequency of the KLOTHO gene G395A mutant was not different between the calcified and noncalcified coronary artery groups (25.7%, 26.4%, respectively, P = 0.861) and an A allele carrier state was not an independent risk factor of coronary artery calcification. In conclusion, the KLOTHO gene G395A allele carrier state may be associated with CAD but not with coronary artery calcification in this Korean population.

The mildly elevated serum bilirubin level is negatively associated with the incidence of end stage renal disease in patients with IgA nephropathy.

Oxidative stress plays various roles in the development and progression of IgA nephropathy, while bilirubin is known as a potent antioxidant. We therefore hypothesized that serum bilirubin would be associated with renal prognosis in IgA nephropathy. The study subjects comprised 1,458 adult patients with primary IgA nephropathy in Korea. We grouped patients according to the following quartile levels of bilirubin: <0.4 mg/dL (Q1), 0.4-0.5 mg/dL (Q2), 0.6-0.7 mg/dL (Q3), and >0.8 mg/dL (Q4). The outcome data were obtained from the Korean Registry of end-stage renal disease (ESRD). Eighty patients (5.5%) contracted ESRD during a mean follow-up period of 44.9 months. The ESRD incidences were 10.7% in Q1, 8.2% in Q2, 2.8% in Q3, and 2.8% in Q4 (p<0.001). The relative risk of ESRD compared to that in Q1 was 0.307 (95% confidence interval [CI], 0.126-0.751) in Q3 and 0.315 (95% CI, 0.130-0.765) in Q4. The differences of ESRD incidence were greater in subgroups of males and of patients aged 35 yr or more, with serum albumin 4.0 g/dL or more, with normotension, with eGFR 60 mL/min/1.73 m(2) or more, and with proteinuria less then 3+ by dipstick test. In conclusion, higher bilirubin level was negatively associated with ESRD incidence in IgA nephropathy.