Incidence and risk factors for tenofovir-associated nephrotoxicity among human immunodeficiency virus-infected patients in Korea

BACKGROUND/AIMS@#Little is known about tenofovir disoproxil fumarate (TDF)-induced nephrotoxicity in human immunodeficiency virus (HIV)-infected patients in Korea. The objective of this study was to evaluate the incidence and risk factors of TDF-associated nephrotoxicity among HIV-infected patients in Korea.@*METHODS@#A single-center retrospective cohort study was conducted on HIV-infected patients in Korea. We included patients who had started TDF or abacavir (ABC)-based antiretroviral therapy (ART) between October 2006 and December 2014. Estimated glomerular filtration rate (eGFR) was estimated using the Chronic Kidney Disease-Epidemiology Collaboration equation. Renal dysfunction was defined as > 25% decrease of baseline eGFR. A propensity matched case-control study was conducted to compare renal dysfunction rates between the two groups. The risk factors of nephrotoxicity were analyzed by Cox regression analysis.@*RESULTS@#A total of 210 HIV-infected patients were included in the study, of which, 108 were TDF-based ART group and 102 were ABC-based ART group. Renal dysfunction occurred in 16 patients (14.8%) in the TDF group and 11 (10.8%) in the ABC group. Incidence of renal dysfunction of TDF and ABC group was 9.66 per 100 person-years (PYs) and 5.14 per 100 PYs, respectively (p = 0.176). In propensity-score-matched analysis, renal dysfunction rates were TDF 13.3% versus ABC 13.3% (p > 0.999). In multivariable analysis, Centers for Disease Control and Prevention clinical category C was a significant risk factor for renal dysfunction.@*CONCLUSIONS@#Approximately, 13% of HIV-infected patients treated with TDF had renal dysfunction. Advanced stage of HIV infection was a significant risk factor for renal dysfunction.

Primary Glomerulonephritis with Unique C4d Deposition and Concurrent Non-infectious Intermediate Uveitis: a Case Report and Literature Review

C4 glomerulopathy is a recently introduced entity that presents with bright C4d staining and minimal or absent immunoglobulin and C3 staining. We report a case of a 62-year-old man with C4 glomerulonephritis (GN) and uveitis. He presented to the nephrology department with proteinuria and hematuria. The patient also had intermediate uveitis along with proteinuria and hematuria. A kidney biopsy that was performed in light of continuing proteinuria and hematuria showed a focal proliferative, focal sclerotic glomerulopathy pattern on light microscopy, absent staining for immunoglobulin or C3 by immunofluorescence microscopy, with bright staining for C4d on immunohistochemistry, and electron-dense deposits on electron microscopy. Consequently, C4 GN was suggested as the pathologic diagnosis. Although laser microdissection and mass spectrometry for glomerular deposit and pathologic evaluation of the retinal tissue were not performed, this is the first report of C4 GN in Korea and the first case of coexisting C4 GN and uveitis in the English literature.

Trends in Malignancies among Korean Patients Infected with Human Immunodeficiency Virus in the Highly Active Antiretroviral Therapy Era

Since the introduction of highly active antiretroviral therapy, the life span of people with human immunodeficiency virus (HIV) or AIDS (PWHA) has been extended significantly. Therefore, the importance of non-AIDS-defining cancers (NADCs), as well as AIDS-defining cancers (ADCs) has increased. There is little information concerning the epidemiology of malignancies in PWHA in Korea. A descriptive epidemiologic study was conducted at a tertiary care hospital in Korea. PWHA who visited Pusan National University Hospital from January 2000 to October 2014 were included. Demographics and clinical data were obtained from the medical records and analyzed. A total of 950 PWHA were observed for 4,439.71 person-years. Forty-eight episodes (5.05%) of cancers were diagnosed in 47 patients. Mean age of the enrolled patients was 40.66 ± 12.15 years and 88% were male. Among the 48 cancer episodes, 20 (42%) were ADCs and 28 were NADCs. The most common ADCs was non-Hodgkin's lymphoma (53.6%), followed by Kaposi's sarcoma (17.9%). The most common NADCs were lung cancer (25%) and hepatocellular carcinoma (25%). The overall incidence of total cancers, ADCs, and NADCs was 10.8 (95% confidence interval [CI], 8.0–14.3), 4.5 (95% CI, 2.8–7.0), and 6.3 (95% CI, 4.2–9.1)/1,000 person-years, respectively. NADCs accounted for 12/15 (80%) of cancers among PWHA with good adherence to care. The 5-year survival rate of PWHA and NADC was 26.3%. NADCs have become the main type of malignancy among Korean PWHA with good adherence to care. Effective strategies to improve screening of NADCs among PWHA are required in Korea.

Incidence and risk factors of hepatitis C virus infection among human immunodeficiency virus (HIV) patients in a large HIV clinic in South Korea

BACKGROUND/AIMS: Increasing incidences of hepatitis C virus (HCV) infection in human immunodeficiency virus (HIV)-infected men who have sex were reported in the United States and Europe. However, few studies regarding the epidemiology of HCV infection in HIV-infected patients in Asian countries have been reported. METHODS: To determine the prevalence and incidence of HCV infection in HIV-infected patients, a retrospective cohort study was conducted. All HIV-infected patients who visited a tertiary care hospital in Korea from 2000 to 2013 were identified. Patients with ≥ 1 HCV antibody (Ab) test were included and observed until December 2014. RESULTS: Among 996 HIV-infected patients, 790 patients (79%) had baseline HCV Ab tests and 41 (5.2%) were positive at baseline and four at follow-up. Experience of injecting drug use (IDU; adjusted odds ratio, 16.20; 95% confidence interval [CI], 1.56 to 167.89; p < 0.01) was significantly associated with prevalent HCV infection. Conversion to HCV Ab positivity was observed in four of 384 included patients, with an incidence rate of 2.22 (95% CI, 0.60 to 5.80)/1,000 person-years (PYs); 164.89 (95% CI, 34.00 to 481.88)/1,000 PYs in patients with IDU, and 1.40 (95% CI, 0.35 to 7.79)/1,000 PYs in men who have sex with men who denied IDU. There was no significant increase in incidence rate of HCV in HIV-infected patients from 2009 to 2014 (p = 0.119). Among 19 patients who were positive for HCV RNA, genotype 1b (73%) was the most common following 2a/2c (20%). CONCLUSIONS: IDU was an independent risk factor for prevalent HCV infection. Prevalence of HCV infection was low and incidence of HCV infection was not significantly increased in HIV-infected patients in South Korea.

Predictors of Poor Retention in Care of HIV-infected Patients Receiving Antiretroviral Therapy in Korea: Five-Year Hospital-based Retrospective Cohort Study

Poor retention in care (RIC) is associated with higher antiretroviral therapy (ART) failure and worse survival. Identifying high risk patients for poor RIC is important for targeted intervention. A retrospective cohort study was conducted at a tertiary care hospital in Korea. HIV-infected patients initiating ART during 2002-2008 were included. 5 year-RIC was measured by hospital visit constancy (HVC) at 5 years after initiating ART. Among 247 enrolled patients, 179 (72.5%) remained in care, 20 (8.1%) were transferred to other hospitals, 9 (3.6%) died and 39 (15.8%) were lost to follow-up. We compared the demographic, psychosocial, and clinical characteristics between the groups with 100% HVC (n = 166, 67.2%) and 50; 95% confidence interval [CI] 1.10-15.15, P = 0.036), no non-HIV related comorbidity (OR 2.94 vs. comorbidity > or = 1; 95% CI 1.02-8.49, P = 0.046), baseline CD4 cell count > 300 cells/muL (OR 3.58 vs. < or = 200; 95% CI 1.33-9.65, P = 0.012) were significant predictable factors of poor RIC. HIV/AIDS care-givers should pay attention to young patients with higher baseline CD4 cell counts and no non-HIV related comorbidity.

Severe Hypernatremia Caused by Acute Exogenous Salt Intake Combined with Primary Hypothyroidism

This report describes a case of severe hypernatremia with a serum sodium concentration of 188.1mmol/L caused by exogenous salt intake. A 26-year-old man diagnosed with Crohn's disease 5 years previously visited our clinic due to generalized edema and personality changes, with aggressive behavior. He had compulsively consumed salts, ingesting approximately 154 g of salt over the last 4 days. Despite careful fluid management that included not only hypotonic fluid therapy for 8 hours but also hypertonic saline administration, his serum sodium level decreased sharply at 40.6 mmol/L; however, it returned to normal within 72-hour of treatment without any neurological deficits. Primary hypothyroidism was also diagnosed. He was discharged after 9 days from admission, with a stable serum sodium level. We have described the possibility of successful treatment in a patient with hypernatremia caused by acute salt intoxication without sustained hypotonic fluid therapy.

Unmasked chronic renal function deterioration after unilateral adrenalectomy in patients with primary aldosteronism

We report 2 cases of chronic estimated glomerular filtration rate (eGFR) decline after unilateral adrenalectomy due to primary aldosteronism. The patients were diagnosed with unilateral adrenal cortical adenoma releasing aldosterone. Two patients were examined for hypertension and hypokalemia. Unilateral laparoscopic adrenalectomy was performed in both cases, and pathology confirmed adrenal cortical adenoma. After adrenalectomy, hypertension and hypokalemia improved to within normal range. However, the eGFR decreased postoperatively, and abdominal computed tomography scan showed decreased kidney size compared to previous images. Kidney biopsy was performed to delineate the exact cause of renal function deterioration and revealed hypertensive changes with chronic interstitial changes, indicating that glomerular hyperfiltration with aldosterone excess masked renal function damage. Physicians have to consider the probability of postadrenalectomy eGFR decline related to chronic hypertensive change.

Is Multi-Drug Resistant Tuberculosis More Prevalent in HIV-Infected Patients in Korea?

The epidemiological synergy between human immunodeficiency virus (HIV) and tuberculosis (TB) is a major threat to public health. However, the association between HIV and multi-drug resistant tuberculosis (MDR-TB) is not clear. To explore the association between HIV and MDR-TB infection, a case-control study was performed in Korea. A total of 1606 culture-proven TB patients (45 HIV vs. 1561 non-HIV) from January 2006 to October 2014 were included in this analysis. MDR-TB rates were 11.1% and 8.2% in the HIV and non-HIV groups, respectively (p=0.42), thus indicating that MDR-TB was not significantly associated with HIV infection in Korea.

Is Multi-Drug Resistant Tuberculosis More Prevalent in HIV-Infected Patients in Korea?

The epidemiological synergy between human immunodeficiency virus (HIV) and tuberculosis (TB) is a major threat to public health. However, the association between HIV and multi-drug resistant tuberculosis (MDR-TB) is not clear. To explore the association between HIV and MDR-TB infection, a case-control study was performed in Korea. A total of 1606 culture-proven TB patients (45 HIV vs. 1561 non-HIV) from January 2006 to October 2014 were included in this analysis. MDR-TB rates were 11.1% and 8.2% in the HIV and non-HIV groups, respectively (p=0.42), thus indicating that MDR-TB was not significantly associated with HIV infection in Korea.

High serum and urine neutrophil gelatinaseassociated lipocalin levels are independent predictors of renal progression in patients with immunoglobulin A nephropathy

BACKGROUND/AIMS: Tubulointerstitial injury plays an important role in the progression of immunoglobulin A nephropathy (IgAN), and neutrophil gelatinase-associated lipocalin (NGAL) is among the most sensitive tubular biomarkers. We investigated whether serum or urine NGAL predicts prognosis in patients with IgAN. METHODS: The present study enrolled patients with biopsy-proven IgAN from January 2005 to December 2010, whose serum and urine samples at the time of kidney biopsy were preserved by freezing. We retrospectively reviewed patient clinical data and followed patients until October 2012. Serum and urine NGAL levels were measured using an enzyme-linked immunosorbent assay kit. Renal progression was defined as an estimated glomerular filtration rate decline by > 50% or progression to end-stage renal disease. RESULTS: There were 121 patients enrolled in this study. During the median follow-up period of 41.49 months, renal progression was found in nine patients (7.4%). Serum or urine NGAL alone could not predict renal progression; however, when serum and urine NGAL levels were combined, belonging to the high NGAL group independently predicted renal progression (hazard ratio [HR], 5.56; 95% confidence interval [CI], 1.42 to 21.73; p = 0.014), along with tubular damage graded according to the Oxford classification as T2 (HR, 8.79; 95% CI, 2.01 to 38.51; p = 0.004). In addition, a Kaplan-Meier curve of renal survival showed significantly higher renal progression in patients in the high NGAL group (log rank, p = 0.004). CONCLUSIONS: In patients with IgAN, high serum and urine NGAL levels at the time of kidney biopsy predict renal progression.

Human Papillomavirus Prevalence and Genotype Distribution among HIV-Infected Women in Korea

The epidemiology on human papillomavirus (HPV) among human immunodeficiency virus (HIV)-infected women in Korea is not well established. A retrospective study was conducted to determine the prevalence and genotype distribution of HPV infection among HIV-infected women in Korea. HPV DNA genotype and cervical cytology were examined in 60 HIV-positive women and 1,938 HIV-negative women. HPV genotypes were analyzed by using a HPV DNA chip. HIV-infected women had higher prevalence of high-risk HPV (hr-HPV) infection (30% vs 4.9%, adjusted odds ratio [AOR], 6.96; 95% confidence interval [CI], 3.63-13.34, P<0.001) and abnormal cervical cytology (18.3% vs 1.8%, AOR, 10.94; 95% CI, 5.18-23.1, P<0.001) compared with controls. The most common hr-HPV genotype detected in HIV-infected women was HPV 16 (10%), followed by 18 (6.7%) and 52 (5%). Prevalence of quadrivalent vaccine-preventable types (HPV 6, 11, 16, and 18) was 21.7% and 2.3% in HIV-positive women and HIV-negative women, respectively. Age was a significant risk factor for hr-HPV infection in HIV-infected women (P=0.039). The presence of hr-HPV was significantly associated with abnormal cervical cytology (P<0.001). These findings suggest that HPV testing for cervical cancer screening in HIV-infected women would be necessary, particularly among young age group.

Comparison of glomerular filtration rates calculated by different serum cystatin C-based equations in patients with chronic kidney disease

BACKGROUND: We aimed to evaluate the performance of serum cystatin C-based equations in calculating the glomerular filtration rate (GFR) in patients with varying stages of chronic kidney disease (CKD). METHODS: Serum cystatin C and creatinine levels were measured in 615 CKD patients. The CKD stage was determined by the creatinine-based estimated GFR (eGFR) equation using the four-variable abbreviated Modification of Diet in Renal Disease equation suggested by the Kidney Disease Outcome Quality Initiative with the addition of a coefficient applicable to Korean populations (K-aMDRD). In each CKD stage, the ratio of serum cystatin C to creatinine was calculated and six different cystatin C-based equations were used to estimate GFR. Cystatin C-based eGFR and aMDRD eGFR values were compared using the paired t test, Pearson correlation test, and the Bland-Altman plot. RESULTS: The mean age of patients was 53.21+/-14.45 years; of the 615 patients, 346 were male. The serum cystatin C-to-creatinine ratio was inversely correlated with the CKD stage. Compared with the K-aMDRD values, the results of the Hoek, Filler, and Le Bricon's cystatin C-based eGFR equations were lower in CKD Stages 1-3 and higher in Stages 4 and 5. However, the results of the Orebro-cystatin (Gentian) equation [GFR=100/ScytC (mL/minute/1.73m2) - 14] were similar to those of the K-aMDRD equation in CKD Stages 4 and 5 (15.44+/-9.45 vs. 15.17+/-9.05mL/minute/1.73m2, respectively; P=0.722; bias=0.27+/-8.87). CONCLUSION: The eGFRs obtained from the six cystatin C-based equations differed widely. Therefore, further studies are required to determine the most accurate equation to estimate GFR in Koreans with CKD.

Significance of residual renal function for phosphate control in chronic hemodialysis patients

BACKGROUND: The aim of this study was to compare mineral metabolism between anuric and nonanuric chronic hemodialysis patients, and determine the differences in phosphate control between the two groups. METHODS: A total of 77 chronic hemodialysis patients were enrolled in this cross-sectional study from January 2012 to February 2012. Patient demographics, laboratory findings, medication histories, and vascular calcification scores were collected. We divided the patients into anuric and nonanuric groups according to the residual renal function and then compared their clinical features. Multivariate binary regression analysis was used in each group to determine the independent factors related to phosphate control. RESULTS: The mean patient age was 59.27+/-13.95 years, and 57.1% of patients were anuric. In anuric patients, dialysis vintage was significantly longer, but the mean Kt/V was not different between groups. Serum phosphate, fibroblast growth factor (FGF)-23, and Ca/P products were significantly higher, and 1,25(OH)2D3 levels were significantly lower in the anuric patients, although the intact parathyroid hormone and 25(OH)D levels were not different. In anuric patients, LnFGF-23 [hazard ratio (HR) 2.894, 95% confidence interval (CI) 1.294-6.474, P=0.010] was an independent factor predictive of phosphate control. However, in the nonanuric patients, glomerular filtration rate (HR 0.409, 95% CI 0.169-0.989, P=0.047) and blood urea nitrogen (HR 1.090, 95% CI 1.014-1.172, P=0.019) were independent factors predictive of phosphate control. CONCLUSION: In chronic hemodialysis patients, preservation of residual renal function is a significant determinant of phosphate control, and the factors associated with phosphate control is different depending on the residual renal function status. In the anuric patients, FGF-23 is most significantly associated with phosphate control; however, glomerular filtration rate and blood urea nitrogen are more important than FGF-23 in the nonanuric HD patients.

Pyeloduodenal Fistula Successfully Treated By Endoscopic Ligation without Surgical Nephrectomy: Case Report

A 74-yr-old woman presented with fever and abdominal discomfort. She was in a septic condition caused by urinary tract infection. Her computed tomogram of the abdomen revealed features of hydronephrosis with ureteral stones in both kidneys. During percutaneous nephrostomies, right pyeloduodenal fistula (PDF) was diagnosed. Elective surgery was originally planned but the patient was in a poor condition to undergo surgery. Instead, 2 times endoscopic clipping and ligation by endoloop were applied with parenteral antibiotics for the fistula lesion. On admission day 30, she was discharged from the hospital after confirmation of no more contrast leakage on fistulography. We reviewed the literature and discuss the etiologies, clinical presentations, diagnosis, and treatment of PDF.

Corrigendum: Use of low-dose sulodexide in IgA nephropathy patients on renin-angiotensin system blockades Volume 31, Issue 3, September 2012, Pages 163-169

The authors regret that, in the above article, one of the co-authors' names was incorrectly printed. It is now reproduced correctly above.

Decreased Renal Function Is an Independent Predictor of Severity of Coronary Artery Disease: An Application of Gensini Score

Coronary artery disease (CAD) is the leading cause of death in patients with chronic kidney disease (CKD).Although many studies have shown a higher prevalence of CAD among these patients, the association between the spectrum of renal dysfunction and severity of CAD remains unclear. In this study, we investigate the association between renal function and the severity of CAD. We retrospectively reviewed the medical records of 1,192 patients who underwent elective coronary angiography (CAG). The severity of CAD was evaluated by Gensini score according to the degree of luminal narrowing and location(s) of obstruction in the involved main coronary artery. In all patients, the estimated glomerular filtration rate (eGFR) was independently associated with Gensini score (beta=-0.27, P < 0.001) in addition to diabetes mellitus (beta=0.07, P = 0.02), hypertension (beta=0.12, P < 0.001), low density lipoprotein (LDL)-cholesterol (beta=0.08, P = 0.003), and hemoglobin (beta=-0.07, P = 0.03) after controlling for other confounding factors. The result of this study demonstrates that decreased renal function is associated not only with the prevalence, but also the severity, of CAD.

Causes of Death and Risk Factors for Mortality among HIV-Infected Patients Receiving Antiretroviral Therapy in Korea

A retrospective study was conducted to determine the mortality, causes and risk factors for death among HIV-infected patients receiving antiretroviral therapy (ART) in Korea. The outcomes were determined by time periods, during the first year of ART and during 1-5 yr after ART initiation, respectively. Patients lost to follow-up were traced to ascertain survival status. Among 327 patients initiating ART during 1998-2006, 68 patients (20.8%) died during 5-yr follow-up periods. Mortality rate per 100 person-years was 8.69 (95% confidence interval, 5.68-12.73) during the first year of ART, which was higher than 4.13 (95% confidence interval, 2.98-5.59) during 1-5 yr after ART. Tuberculosis was the most common cause of death in both periods (30.8% within the first year of ART and 16.7% during 1-5 yr after ART). During the first year of ART, clinical category B and C at ART initiation, and underlying malignancy were significant risk factors for mortality. Between 1 and 5 yr after ART initiation, CD4 cell count < or = 50 cells/microL at ART initiation, hepatitis B virus co-infection, and visit constancy < or = 50% were significant risk factors for death. This suggests that different strategies to reduce mortality according to the time period after ART initiation are needed.

Trends of Mortality and Cause of Death among HIV-Infected Patients in Korea, 1990-2011

Although a decrease in acquired immunodeficiency syndrome (AIDS)-related mortality has been documented in highly active antiretroviral therapy (HAART) era, there are no published data comparing specific causes of death between pre-HAART and HAART era in Korea. Mortality and cause of death were analyzed in three treatment periods; pre-HAART (1990-1997), early-HAART (1998-2001), and late-HAART period (2002-2011). The patients were retrospectively classified according to the treatment period in which they were recruited. Although mortality rate per 100 person-year declined from 8.7 in pre-HAART to 4.9 in late-HAART period, the proportion of deaths within 3 months of initial visit to study hospital significantly increased from 15.9% in pre-HAART to 55.1% in late-HAART period (P < 0.001). Overall, 59% of deaths were attributable to AIDS-related conditions, and Pneumocystis pneumonia (PCP) was the most common cause of death (20.3%). The proportion of PCP as cause of death significantly increased from 8.7% in pre-HAART to 31.8% in late-HAART period (P < 0.001). Despite of significant improvement of survival, there was still a high risk of early death in patients presenting in HAART era, mainly due to late human immunodeficiency virus (HIV) diagnosis and late presentation to care.

25-Hydroxyvitamin D Status Based on Estimated Glomerular Filtration Rate in Patients with Chronic Kidney Disease / 대한내과학회지

BACKGROUND/AIMS: Accumulating data suggest that vitamin D deficiency is prevalent in patients with chronic kidney disease (CKD). However, comprehensive data are lacking for Koreans. The aim of this study was to survey vitamin D deficiency among patients with CKD in Korea and to identify the relationships among various factors. METHODS: We conducted a retrospective cohort study of 444 patients who were divided into four subgroups by estimated glomerular filtration rate (eGFR) for comparisons of mean 25-hydroxyvitamin D [25(OH)D] level and other parameters. In addition, non-dialyzed patients were categorized into four groups based on 25(OH)D levels ( or =30 ng/mL), and risk factors for severe vitamin D deficiency ( or = 60 mL/min/1.73 m2, 43% (34/79) showed severe 25(OH)D deficiency, and the mean 25(OH)D level was 11.7 +/- 5.3 ng/mL. In CKD3 group, 53.2% (41/77) showed severe 25(OH)D deficiency, with a mean level of 11.3 +/- 7.2 ng/mL. In CKD4 group, 53.3% (49/92) had severe 25(OH)D deficiency, with a mean level of 11.0 +/- 6.2 ng/mL. Approximately 71% (139/196) of patients in CKD5 group showed severe deficiency, and the mean level was 9.2 +/- 5.9 ng/mL. Severe 25(OH)D deficiency was affected by winter season, renal function, diabetes, and low-density lipoprotein cholesterol. The serum parathyroid hormone level was inversely correlated with the 25(OH)D level, such that 25(OH)D <20 ng/mL were associated with a steep increase in parathyroid hormone. CONCLUSIONS: Vitamin D deficiency is highly prevalent in the Korean population. Few patients met a sufficient 25(OH)D concentration, even in the early stages of CKD. Our data suggest that 25(OH)D level of 20 ng/mL is a threshold for a rapid increase in parathyroid hormone levels.

A Case of Severe Acute Kidney Injury by Near-Drowning

Acute kidney injury (AKI) secondary to near-drowning is rarely described and poorly understood. Only few cases of severe isolated AKI resulting from near-drowning exist in the literature. We report a case of near-drowning who developed to isolated AKI due to acute tubular necrosis (ATN) requiring dialysis. A 21-yr-old man who recovered from near-drowning in freshwater 3 days earlier was admitted to our hospital with anuria and elevated level of serum creatinine. He needed five sessions of hemodialysis and then renal function recovered spontaneously. Renal biopsy confirmed ATN. We review the existing literature on near-drowning-induced AKI and discuss the possible pathogenesis.