Wookyung Chung

Benefits of biocompatible PD fluid for preservation of residual renal function in incident CAPD patients: a 1-year study

BACKGROUND In vitro studies of peritoneal dialysis (PD) solutions demonstrated that a biocompatible fluid with neutral-pH and low glucose degradation products (LF) has better biocompatibility than a conventional acidic lactate-buffered fluid (CF). However, few clinical trials have investigated the effects of the biocompatible solution on residual renal function (RRF). We performed a prospective, randomized trial with patients starting continuous ambulatory peritoneal dialysis (CAPD). METHODS Ninety-one incident patients started CAPD for 12-month treatment with either LF (Balance, Fresenius, n = 48) or CF (CAPD/DPCA, Fresenius, n = 43). RRF, peritoneal solute transport rate and solute clearance were measured every 6 months. RESULTS LF had a significant effect on the change of glomerular filtration rate (GFR) (P = 0.048 by the mixed model). In per-protocol analysis, GFR in the LF group did not decrease over a 12-month period, while GFR in the control group significantly decreased (0.13 +/- 33.4 L/ week/1.73 m(2) for LF versus -13.6 +/- 19.4 L/week/1.73 m(2) for CF, P = 0.049). Subgroup analysis for patients with initial GFR of 2 mL/min/1.73 m(2) or above showed a significantly higher GFR for the LF group over the 12-month period. At Month 13, serum total CO(2) levels were higher and serum albumin levels were lower in the LF group. No differences between the two groups were observed for the C-reactive protein. Over the 12-month period, effluent cancer antigen-125 levels significantly increased in the LF group, compared with those of the CF group, while effluent interleukin-6 levels were not different between the two groups. CONCLUSION Our study suggests that LF may better preserve RRF over the 12-month treatment period in incident CAPD patients.

Single Nucleotide Polymorphisms in the Phospholipase A2 Receptor Gene Are Associated with Genetic Susceptibility to Idiopathic Membranous Nephropathy

Background: The phospholipase A2 receptor (PLA2R) is a major antigen found in patients with idiopathic membranous nephropathy (MN). The relationship of genetic polymorphisms of PLA2R with the susceptibility and clinical outcomes of this disease is unknown. Methods: We studied 199 patients with idiopathic MN followed up for 3.7 ± 3.2 years. We enrolled 33 patients with secondary MN and 356 subjects with normal blood pressure and no proteinuria. PLA2R single nucleotide polymorphisms (SNPs) were genotyped. Results: The allele frequencies of C in rs35771982 and G in rs3828323 were 73.6 and 73.9%, respectively. Subjects with the CC genotype in rs35771982 had a higher susceptibility to idiopathic MN compared to subjects with other genotypes (odds ratio 2.6; 95% confidence interval 1.8–4.0). Patients with secondary MN were not different from controls with regard to PLA2R genotype. No impact of genetic polymorphisms on renal survival was detected. Conclusion: The findings of this study suggest that PLA2R SNPs might be associated with the risk of developing MN.

The Effect of Renin-Angiotensin-Aldosterone System Blockade on Contrast-Induced Acute Kidney Injury: A Propensity-Matched Study

BACKGROUND The role of the angiotensin-converting enzyme (ACE) inhibitor and angiotensin receptor blocker (ARB) in the pathophysiology of contrast-induced acute kidney injury (AKI) is controversial, and the available literature is contradictory. STUDY DESIGN A retrospective propensity score-matched study to analyze the effect of ACE-inhibitor/ARB therapy on the development of contrast-induced AKI. SETTING & PARTICIPANTS Using propensity score matching, 1,322 ACE-inhibitor/ARB recipients and nonrecipients were paired for analysis from 5,299 patients and fulfilled the inclusion criteria among 11,447 patients receiving coronary angiography (CAG) or percutaneous coronary intervention. PREDICTORS ACE-inhibitor/ARB use based on prescription and risk factors for contrast-induced AKI. OUTCOMES The incidence of contrast-induced AKI defined by AKI Network (AKIN) criteria: an absolute increase in serum creatinine levels ≥0.3 mg/dL or a relative increase ≥50% from baseline values within 48 hours after exposure to the contrast medium. MEASUREMENTS Baseline serum creatinine, hemoglobin, and albumin levels; volume of contrast agents; preprocedural medication; and post-CAG serum creatinine levels. RESULTS An ACE inhibitor/ARB was prescribed for 64.0% of patients receiving CAG. ACE-inhibitor/ARB users showed an increased incidence of contrast-induced AKI after propensity score matching (11.4% vs 6.3%; P < 0.001). In multivariable analysis, use of ACE inhibitors/ARBs remained an independent and significant predictor of contrast-induced AKI in an unmatched cohort (OR, 1.39; 95% CI, 1.10-1.76; P = 0.06). In the matched cohort, use of ACE inhibitors/ARBs also was associated with a higher adjusted OR of contrast-induced AKI (OR, 1.43; 95% CI, 1.06-1.94; P = 0.02). LIMITATIONS A retrospective study at a single center. CONCLUSIONS Use of ACE inhibitors/ARBs during CAG has a possible influence to increase the incidence of contrast-induced AKI. Further randomized clinical trials are warranted to confirm the effect of ACE-inhibitor/ARB therapy on the development of contrast-induced AKI.

Chronic Kidney Disease in Cancer Patients: An Independent Predictor of Cancer-Specific Mortality

Background/Aims: The effects of chronic kidney disease (CKD) on the risk of death for patients with malignant disease are uncertain. The aim of this study was to determine the association between the presence of CKD and mortality in cancer patients. Method: We retrospectively reviewed the cases of 8,223 cancer patients with one or more serum creatinine measurements from January 1, 2000 to December 31, 2004. The key outcome was cancer-specific mortality within the follow-up period. The cumulative incidence rate for death from cancer was estimated using methods of competing risks survival analysis. Cox proportional-hazards regression with the use of Fine and Gray’s proportional-hazards model were evaluated in multiple analyses. Results: CKD was associated with an increased risk of death in cancer patients. The adjusted hazard ratios were 1.12 for patients with an estimated glomerular filtration rate (eGFR) of 30–59 ml/min/1.73 m2 (95% confidence interval 1.01–1.26, p = 0.04) and 1.75 for patients with an eGFR <30 ml/min/1.73 m2 (95% confidence interval 1.32–2.32, p < 0.001). Conclusions: CKD should be considered a risk factor for survival among patients with cancer.

Low-Dose Aspirin for Prevention of Cardiovascular Disease in Patients with Chronic Kidney Disease

Background Chronic kidney disease (CKD) is a major risk factor for the development of cardiovascular disease (CVD). Previous trials have investigated the effects of low-dose aspirin on CVD prevention in patients with diabetes; however, patients with CKD were not examined. The role of aspirin in diabetics is controversial, and the available literature is contradictory. Therefore, we studied whether low-dose aspirin would be beneficial for patients with CKD, a group that is at high risk for CVD. Method From a total of 25340 patients with CKD, 1884 recipients of low-dose aspirin (100 mg/day) were paired 1∶1 with non-recipients for analysis using propensity score matching. The primary endpoint was the development of atherosclerotic CVD, including coronary arterial disease, stroke, and peripheral arterial disease. Secondary endpoints included death from any cause, bleeding events, doubling of serum creatinine, and renal death. Results The incidence of a primary endpoint of any atherosclerotic CVD was significantly higher in the aspirin users than in the non-users (P<0.001). Secondary endpoints, including all-cause mortality and composite bleeding events, were not significantly different between the aspirin users and the non-users. However, the doubling of serum creatinine levels (P = 0.001) and renal death (P = 0.042) were significantly associated with the use of aspirin. Conclusion These results suggest that the use of low-dose aspirin in patients with CKD may have harmful consequences related to the development of CVD and renal progression.

The clinicopathological relevance of pretransplant anti-angiotensin II type 1 receptor antibodies in renal transplantation

Background Anti-angiotensin II type 1 receptor antibodies (AT1R-Abs) have been suggested as a risk factor for graft failure and acute rejection (AR). However, the prevalence and clinical significance of pretransplant AT1R-Abs have seldom been evaluated in Asia. Methods In this multicenter, observational cohort study, we tested the AT1R-Abs in pretransplant serum samples obtained from 166 kidney transplant recipients. Statistical analysis was used to set a threshold AT1R-Abs level at 9.05 U/mL. Results Pretransplant AT1R-Abs were detected in 98/166 (59.0%) of the analyzed recipients. No graft loss or patient death was reported during the study period. AT1R-Abs (+) patients had a significantly higher incidence of biopsy-proven AR than AT1R-Abs (-) patients (27.6 versus 10.3%, P = 0.007). Recipients with pretransplant AT1R-Abs had a 3.2-fold higher risk of AR within a year of transplantation (P = 0.006). Five study subjects developed microcirculation inflammation (score ≥2). Four of them were presensitized to AT1R-Abs. In particular, three patients had a high titer of anti-AT1R-Abs (>22.7 U/mL). Conclusions Pretransplant AT1R-Abs is an independent risk factor for AR, especially acute cellular rejection, and is possibly associated with the risk of antibody-mediated injury. Pretransplant assessment of AT1R-Abs may be useful for stratifying immunologic risks.

Circulating levels of soluble receptor for advanced glycation end product are inversely associated with vascular calcification in patients on haemodialysis independent of S100A12 (EN-RAGE) levels.

The receptor for advanced glycation end products (RAGE) has emerged as a central regulator of vascular inflammation and atherosclerosis. Soluble RAGE (sRAGE) has an anti‐inflammatory effect by quenching ligands for RAGE. On the other hand, extracellular RAGE‐binding protein S100A12 (EN‐RAGE) shows a pro‐inflammatory effect in a way, but may play pleiotropic roles related to inflammatory process. Therefore, we determined the levels of sRAGE and S100A12 in haemodialysis (HD) patients and evaluated their relationship with vascular calcification.

Hyperuricemia Is an Independent Risk Factor for Mortality Only if Chronic Kidney Disease Is Present

Background/Aims: Hyperuricemia has been considered a risk factor for renal disease and cardiovascular disease. However, the potential contribution of hyperuricemia to mortality remains uncertain, and the results in the available literature vary according to kidney function. The aim of this study was to determine the association between hyperuricemia and mortality in patients undergoing percutaneous coronary intervention (PCI) across the interaction of kidney function. Method: We retrospectively reviewed patients who underwent PCI from 2003 to 2009. Propensity scores for hyperuricemia (>7 mg/dl for males and >6 mg/dl for females) were used to assemble a matched cohort of 693 pairs of patients with and without hyperuricemia for analysis from the 3,201 patients who fulfilled the inclusion criteria among the 4,842 patients who underwent PCI. Results: Of the 3,201 patients who underwent PCI and for whom data were available regarding their baseline serum uric acid level, 763 (23.8%) had hyperuricemia. The hyperuricemia-associated hazard ratios (HRs) [95% confidence intervals (CIs)] for all-cause mortality were 1.780 (1.270-2.495) in the unmatched cohort and 1.655 (1.109-2.468) in the matched cohort. The HRs (95% CI) for all-cause mortality among those with and without chronic kidney disease (CKD) were 2.080 (1.318-3.283) and 1.592 (0.778-3.256), respectively (p for interaction, 0.001). Conclusions: Hyperuricemia is an independent risk factor for all-cause mortality in those patients with CKD but not in those without CKD.

Donor-Recipient Age Difference and Graft Survival in Living Donor Kidney Transplantation

BACKGROUND In paired living kidney exchange donation from an old donor to a young recipient, it may be argued that elderly donors provide an inferior quality kidney. However, the impact of donors older than recipients on transplant outcomes remains unclear. METHODS We retrospectively reviewed the charts of primary living kidney transplantation patients who were divided into two groups based on the age difference between donor and recipient (recipient age subtracted from donor age, donor-recipient < 20 vs ≥ 20). The donor-recipient age difference < 20 group comprised 75 and donor-recipient age difference ≥ 20 group, 25 subjects. Outcome measures included serum creatinine, acute rejection episodes as well as graft and patient survivals at 1 and 5 years after transplantation. RESULTS The mean donor age difference cohorts of < 20 and ≥ 20 years showed donor ages of 33 ± 8 and 54 ± 8 years, respectively. The mean recipient age in both groups averaged under 40 years. The acute rejection rate within the first year posttransplantation was greater among age difference ≥ 20 years. The mean serum creatinine values of the donor-recipient age difference < 20 group was lower than the ≥20 years group at 1 and 5 years posttransplant. The 1-year difference was associated with an increased creatinine value at 5 years. However, death-censored graft survival of the age difference of the ≥ 20 years group was not different (hazard ratio [HR] = 0.1, 95% confidence interval [CI] = 0.01-1.37, P = .08). Patient survival of the age difference ≥ 20 years group showed no difference compared with the age difference < 20 years group (HR = 0.25, 95% CI = 0.01-6.35, P = .4). CONCLUSION Although the cohort of a donor-young recipient age difference ≥ 20 years showed a greater risk of an acute rejection episode early posttransplantation, it did not affect graft or patient survivals. When considering paired kidney donation, older age donors should not necessarily be limited.

De Novo Hypokalemia in Incident Peritoneal Dialysis Patients: A 1-Year Observational Study

Hypokalemia occurs frequently in patients undergoing peritoneal dialysis (PD). However, the therapeutic strategy may differ from that of non-PD-related hypokalemia. We investigated clinical features and related factors of de novo hypokalemia in incident PD patients. We retrospectively enrolled 82 normokalemic patients starting PD at Gachon University Gil Hospital, Korea. The patients were divided into hypokalemia (K+<3.5 mEq/L) and normokalemia (3.5 mEq/L≤K+<5.5 mEq/L) groups based on the plasma potassium levels at month 13, and then clinical parameters including peritoneal function and adequacy tests and biochemical parameters were compared. Eight patients who showed hyperkalemia (K+≥5.5 mEq/L) at month 13 were excluded from our analyses. The incidence of hypokalemia in PD patients was 7.3% in a year. The de novo hypokalemia (n=6) and normokalemia (n=68) groups had no significant differences in baseline characteristics. The serum albumin levels and normalized protein equivalent of nitrogen appearance (nPNA) at month 1 were not significantly different between the two groups. At month 13, on the other hand, serum albumin levels and nPNA were significantly lower in the hypokalemia group (P=0.014; P=0.006, respectively). Kt/Vurea, residual renal function, dialysate-peritoneal creatinine ratio, and glucose load were not significantly different between the two groups. Hypokalemia occurring after initiation of PD may largely be associated with poor nutritional status.