Jia-Jung Lee

Association of hepatitis C and B virus infection with CKD in an endemic area in Taiwan: a cross-sectional study.

BACKGROUND Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections may lead to nephropathy. However, the association between different types of viral hepatitis and chronic kidney disease (CKD) is not well established. STUDY DESIGN Cross-sectional study. SETTING & PARTICIPANTS A large-scale community study with 54,966 adults in a Taiwanese county endemic for HBV and HCV infection. PREDICTOR HCV infection alone, HBV infection alone, HBV/HCV coinfection, and neither. OUTCOMES Proteinuria (urine protein, >or=1+), low (<60 mL/min/1.73 m(2)) estimated glomerular filtration rate (eGFR), and CKD (proteinuria or eGFR <60 mL/min/1.73 m(2)). MEASUREMENTS HBV and HCV infection were defined as a seropositive test result for hepatitis B surface antigen and HCV antibody. Proteinuria was assessed using a repeated dipstick method. eGFR was computed using the 4-variable Modification of Diet in Renal Disease (MDRD) Study equation. RESULTS Mean age of the study group was 60.8 years. Prevalences of HCV infection alone, HBV infection alone, HBV/HCV coinfection, and neither were 9.4%, 9.9%, 0.9%, and 79.8%, respectively. 2,994 (5.4%), 7,936 (14.5%), and 9,602 (17.5%) participants had proteinuria, low eGFR, and CKD, respectively. Multivariate logistic regression analyses showed that HCV infection alone (OR, 1.26; 95% CI, 1.17-1.38), but not HBV infection alone (OR, 1.04; 95% CI, 0.96-1.14) or HBV/HCV coinfection (OR, 1.12; 95% CI, 0.87-1.45), was an independent risk factor for CKD. The prevalence of HCV seropositivity was higher in later CKD stages, changing from 8.5% in CKD stage 1 to 14.5% in CKD stages 4-5. Adjusted ORs for HCV infection alone were 1.14 (95% CI, 1.003-1.300) for proteinuria and 1.30 (95% CI, 1.20-1.42) for low eGFR. LIMITATIONS The definition of CKD status requires a 3-month duration of low eGFR or kidney damage; this was presumed, not documented, in this study. CONCLUSIONS HCV infection, but not HBV infection, was associated significantly with prevalence and disease severity of CKD in this HBV and HCV endemic area.

Hepatitis C Virus Infection Increases Risk of Developing End-Stage Renal Disease Using Competing Risk Analysis

Background Chronic kidney disease (CKD) and hepatitis C virus (HCV) infection are closely linked and both increase patient mortality. The association of HCV and risk of developing end-stage renal disease (ESRD) has not been analyzed with competing risk model. Method We enrolled a prospective cohort of 4,185 patients (mean age, 62 years; 41% female) registered in the CKD integrated care program at two affiliated hospitals of Kaohsiung Medical University in Taiwan between November 11, 2002 and May 31, 2009. With competing risk model, we analyzed the association of HCV infection, defined by seropositive of anti-HCV antibody, and hepatitis B virus (HBV) infection, defined by seropositive of HBV surface antigen, with the risk of entering ESRD. Results The prevalence of HCV infection was 7.6% and it increased with the CKD stages (trend test, P<0.001), while the prevalence of HBV infection was 7.4% and no specific trend among CKD stages (tend test, P = 0.1). During the 9,101 person-year follow-up period, there were 446 death and 1,205 patients entering ESRD. After adjusting death as the competing risk, the estimated 5-year cumulative incidence rate of ESRD among patients with and without HCV infection were 52.6% and 38.4%, respectively (modified log-rank, P<0.001). Multivariable analysis showed that HCV infection, but not HBV infection, had higher risk of developing ESRD compared with cases without infection (HCV, HR: 1.32, 95% CI: 1.07–1.62; HBV, HR: 1.10, 95% CI: 0.89–1.35). Subgroup analyses showed consistent results. Conclusions With death-adjusted competing risk analysis, HCV infection is associated with an increased risk of developing ESRD in CKD cohort.

Association of Dyslipidemia with Renal Outcomes in Chronic Kidney Disease

Dyslipidemia is highly prevalent in patients with chronic kidney disease (CKD) and the relationship between dyslipidemia with renal outcomes in patients with moderate to advanced CKD remains controversial. Hence, our objective is to determine whether dyslipidemia is independently associated with rapid renal progression and progression to renal replacement therapy (RRT) in CKD patients. The study analyzed the association between lipid profile, RRT, and rapid renal progression (estimated glomerular filtration rate [eGFR] slope <−6 ml/min/1.73 m2/yr) in 3303 patients with stages 3 to 5 CKD. During a median 2.8-year follow-up, 1080 (32.3%) participants commenced RRT and 841 (25.5%) had rapid renal progression. In the adjusted models, the lowest quintile (hazard ratios [HR], 1.23; 95% confidence interval [CI], 1.01 to 1.49) and the highest two quintiles of total cholesterol (HR, 1.25; 95% CI, 1.02 to 1.52 and HR, 1.35; 95% CI, 1.11 to 1.65 respectively) increased risks for RRT (vs. quintile 2). Besides, the highest quintile of total cholesterol was independently associated with rapid renal progression (odds ratio, 1.36; 95% CI, 1.01 to 1.83). Our study demonstrated that certain levels of dyslipidemia were independently associated with RRT and rapid renal progression in CKD stage 3–5. Assessment of lipid profile may help identify high risk groups with adverse renal outcomes.

High hepatitis B virus surface antigen levels and favorable interleukin 28B genotype predict spontaneous hepatitis C virus clearance in uremic patients

BACKGROUND & AIMS Host and viral factors interplay in the spontaneous clearance of hepatitis C virus (HCV) infection. We aimed to explore the roles of IL28B genotypes and hepatitis B virus (HBV) infections in spontaneous HCV seroclearance. METHODS IL28B rs8099917 genotypes, HCV and HBV markers were determined in 290 patients who were seropositive for HCV antibodies from 1681 total uremic patients on maintenance hemodialysis. RESULTS Persistent HCV viremia was observed in 74.6% (214/287) of patients. Logistic regression revealed that the strongest factors associated with spontaneous HCV seroclearance were carriage of rs8099917 TT-type (odds ratio/95% confidence intervals [OR/CI]: 6.22/1.41-27.35, p=0.016), followed by concurrent hepatitis B surface antigen (HBsAg) seropositivity (OR/CI: 2.37/1.06-5.26, p=0.035). The clearance rate was highest among patients with both positive HBsAg/rs8099917 TT-type (44.8%, OR/CI: 20.88/3.5-402.5), followed by positive HBsAg/rs8099917 non-TT-type (28.6%, OR/CI: 8.86/1.8-160.8), and negative HBsAg/rs8099917 TT-type (26.7%, OR/CI: 12.75/1.0-319.4), compared to 4% of negative HBsAg/rs8099917 non-TT-type (trend p=0.0002). HBsAg levels, but not HBV DNA levels, were significantly associated with spontaneous HCV seroclearance. Spontaneous HCV seroclearance rate was 58.3% in patients with HBsAg>200IU/ml/rs8099917 TT-type (OR/CI: 42.54/5.7-908.4), 28.0% in patients with HBsAg<200IU/ml/rs8099917 TT-type or HBsAg>200IU/ml/rs8099917 non-TT-type (OR/CI: 11.12/2.3-201.0), compared to only 3.3% in those with HBsAg<200IU/ml/rs8099917 non-TT-type (trend p=0.0004). Five of 214 (2.3%) HCV viremic patients at enrollment had spontaneous HCV seroclearance during one-year follow-up, which was associated with baseline HCV RNA and HBsAg levels. CONCLUSIONS High HBsAg levels and favorable IL28B genotype were additively associated with spontaneous HCV seroclearance in uremic patients.

FALSE ELEVATION OF BLOOD GLUCOSE LEVELS MEASURED BY GDH-PQQ-BASED GLUCOMETERS OCCURS DURING ALL DAILY DWELLS IN PERITONEAL DIALYSIS PATIENTS USING ICODEXTRIN

♦ Objective: False elevation of blood glucose levels measured by glucose dehydrogenase pyrroloquinoline quinone (GDH-PQQ)-based glucose self-monitoring systems; glucometer) in peritoneal dialysis (PD) patients using icodextrin solution has been well documented. However, adverse hypoglycemic events caused by misreadings for blood glucose are still being reported. We aimed to study blood glucose levels measured simultaneously using different methods in PD patients with switching of icodextrin, and throughout daily exchanges either using icodextrin or not. ♦ Design: We recruited 100 PD patients, including 40 using icodextrin; 128 hemodialysis patients served as a reference. Fasting serum glucose was measured using our laboratory reference method (LAB) and 2 glucose self-monitoring systems based on glucose dehydrogenase nicotinamide adenine dinucleotide (GDH-NAD) and GDH-PQQ respectively. 80 PD patients had a second follow-up study. A time course study was performed in 16 PD patients through measuring fingertip glucose using the 2 glucose self-monitoring systems during daily exchanges. ♦ Result: The differences in measured serum glucose levels in (PQQ minus LAB) versus (NAD minus LAB) were markedly increased in PD patients using icodextrin compared to other patient groups, and was further confirmed by the follow-up study in patients that switched to icodextrin. The high serum glucose levels measured by the GDH-PQQ-based glucose self-monitoring system were present throughout all exchanges during the day in patients using icodextrin solution. ♦ Conclusion: False elevation of blood glucose measured by GDH-PQQ-based glucose self-monitoring systems exists in patients using icodextrin. To avoid misinterpretation of hyperglycemia and subsequent over-injection of insulin, GDH-PQQ-based glucose self-monitoring systems should not be used in PD patients.

Glycated Hemoglobin and Outcomes in Patients with Advanced Diabetic Chronic Kidney Disease.

Diabetes is the major risk factor for end-stage renal disease (ESRD) worldwide. In advanced chronic kidney disease (CKD), less is known about the predictive value of HbA1c. We enrolled 2401 diabetic patients with stage 3–4 and stage 5 CKD, who were classified into 4 groups according to their baseline HbA1c values (<6%, 6%–7%, 7%–9%, and >9%). During the median follow-up of 3 years, 895 patients developed ESRD, and 530 died. In linear regression analysis, higher HbA1c correlated with higher eGFR in patients with stage 5 CKD but not in stage 3–4 CKD. In Cox regression analysis, a trend toward worse clinical outcomes existed when the HbA1c level exceeded 6% in stage 3–4 CKD, but the significance was only observed for >9%. The hazard ratios (HRs) for ESRD, all-cause mortality and combined CV events with mortality in the group of HbA1c >9% were 1.6 (95% CI, 1.07 to 2.38), 1.52 (95% CI, 0.97 to 2.38) and 1.46 (95% CI, 1.02 to 2.09), respectively. This study demonstrates that the higher HbA1c level is associated higher risks for clinical outcomes in diabetic patients with stage 3–4 CKD but not in stage 5 CKD.

Systolic Blood Pressure and Outcomes in Stage 3–4 Chronic Kidney Disease Patients: Evidence from a Taiwanese Cohort

BACKGROUND Systolic blood pressure (SBP) goal for chronic kidney disease (CKD) patients is ≤140mm Hg. However, the SBP target provides no suggested lower limit, and some studies indicate that a lower SBP target may be harmful. We aimed to investigate the J-shaped relationship between SBP and clinical outcomes in CKD patients and the factors that modify this relationship. METHODS This prospective observational study enrolled 2,144 CKD stage 3-4 patients between November 2002 and May 2009 and followed them until July 2010 or death. Patients included were also enrolled within the Integrated CKD Care Program for Delaying Dialysis in a medical center and its branch hospital. Demographic, clinical, laboratory, and disease variables at baseline and end of observation were measured. RESULTS In diabetic CKD patients, the hazard ratio (HR) at SBP 96-110mm Hg vs. 111-120mm Hg was 2.52 (95% confidence interval (CI) = 1.13-5.58) for cardiovascular outcomes and was 3.14 (95% CI = 1.16-8.49) for renal outcomes. In nondiabetic CKD patients, this J-shaped relationship was not seen. Heavy proteinuria was further found to modify the J-shaped relationship in diabetic CKD patients. The HR for renal outcomes at SBP 96-110mm Hg vs. 111-120mm Hg was 4.07 (95% CI = 1.18-13.99) in diabetic CKD patients with heavy proteinuria vs. 1.72 (95% CI = 0.13-22.5) in those without heavy proteinuria. CONCLUSIONS Diabetic CKD patients have a J-shaped relationship between SBP and cardiovascular or renal outcomes, but nondiabetic CKD patients do not. The optimal SBP range might be narrower in the diabetic CKD patients.

Association of Cholesterol Levels with Mortality and Cardiovascular Events among Patients with CKD and Different Amounts of Proteinuria

BACKGROUND AND OBJECTIVES Malnutrition and/or inflammation may modify the risk relationship of total cholesterol with cardiovascular disease in CKD patients. However, it is unclear whether the relationship of total cholesterol with cardiovascular events and mortality varies by proteinuria. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This study enrolled 3303 patients with CKD stages 3-5 from a medical center and a regional hospital between November of 2002 and May of 2009 and followed the patients until July of 2010. RESULTS During a median 2.8-year follow-up, there were 471 (14.3%) deaths and 545 (16.5%) cardiovascular events. In an adjusted Cox model, the two highest quartiles of total cholesterol (hazard ratio, 1.90; 95% confidence interval, 1.16 to 3.13 and hazard ratio, 2.00; 95% confidence interval, 1.18 to 3.39 versus quartile 1, respectively) were associated with a significant higher risk of all-cause mortality in patients with urine protein-to-creatinine ratio<1 g/g (n=1535), but this higher risk was not seen in those patients with urine protein-to-creatinine ratio ≥ 1 g/g (n=1768; hazard ratio, 0.75; 95% confidence interval, 0.53 to 1.07 and hazard ratio, 0.70; 95% confidence interval, 0.49 to 1.02 versus quartile 1, respectively). The interaction between total cholesterol and proteinuria with all-cause mortality was significant (interaction, P=0.05). However, the relationship between total cholesterol and cardiovascular events did not significantly differ by proteinuria (interaction, P=0.91). CONCLUSIONS The association between cholesterol and mortality is different among patients with different levels of proteinuria. Large-scale clinical trials to evaluate the mortality benefit should specifically target lowering hypercholesterolemia in CKD patients with different levels of proteinuria.

Heart Rate Variability Predicts Major Adverse Cardiovascular Events and Hospitalization in Maintenance Hemodialysis Patients

Background/Aims: Heart rate variability (HRV) has been linked to mortality in maintenance hemodialysis (HD) patients, but it is less clear whether HRV is associated with major adverse cardiovascular events (MACEs) and hospitalization. Methods: This study enrolled 179 maintenance HD patients. HRV was measured to assess its prognostic significance in relation to MACEs and hospitalization. Results: During the follow-up period of 33.3 ± 6.7 months, 36 (20.1%) patients had a MACE, and 98 (54.7%) experienced hospitalization. In multivariate adjusted Cox regression analysis, low very low frequency (VLF) power (hazard ratio [HR], 0.727; 95% confidence interval [CI], 0.624–0.848; p < 0.001), a history of coronary artery disease, high ultrafiltration rate, the use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, and the use of beta-blockers were all significantly associated with MACEs. Low VLF power (HR, 0.873; 95% CI, 0.785–0.971; p = 0.012), low serum albumin, low serum creatinine, low Kt/V levels, and high serum calcium-phosphorus product levels significantly predicted hospitalization in maintenance HD patients. Conclusions: Reduced VLF power is linked to an increased risk of MACEs and hospitalization in maintenance HD patients. Assessing cardiac autonomic function through HRV is of pivotal prognostic significance for this patient population.

Acyclovir‐induced acute renal failure

SUMMARY: Acyclovir is an effective antiviral agent in the treatment of herpes simplex and varicella‐zoster viral infections. the best known side‐effects of this drug are significant nephrotoxicity and neurotoxicity. We report on a diabetic patient with acute retinal necrosis who developed non‐oliguric acute renal failure during the administration of high doses of intravenous acyclovir (500 mg/m2 intravenous infusion every 8h). No obvious uremic symptoms or signs were noted. No obvious haematuria, proteinuria or crystalluria were noted in the urine. After discontinuing the acyclovir administration, renal function partially recovered. In this paper, we also review the mechanism of acyclovir‐induced acute renal failure, and the precipitating factor of acyclovir‐induced acute renal failure. Finally, we must once again emphasize the importance of hydration and routine check ups for renal function in preventing acyclovir‐induced acute renal failure.