Family-based genome-wide association analysis of novelty seeking in a Korean schizophrenic population: A pilot study.

Schizophrenia (SPR) is the most devastating mental illness that causes severe deterioration in social and occupational functioning, but, the etiology remains unknown. The objective of this study is to explore the genetic underpinnings of novelty seeking behavior in schizophrenic family within the Korean population. By conducting a family-based genome-wide association study, we aim to identify potential genetic markers and variations associated with novelty seeking traits in the context of SPR. We have recruited 27 probands (with SPR) with their parents and siblings whenever possible. DNA was extracted from blood sampling of 58 individuals in 27 families and analyzed in an Illumina core exome single nucleotide polymorphism (SNP) array. A family-based association test (qFAM) was used to derive SNP association values across all chromosomes. Although none of the final 800,000 SNPs reached the genome-wide significant threshold of 8.45 × 10-7, the most significant 4 SNPs were within the 10-5 to 10-7. This study identifies genetic associations between novelty seeking behavior and SPR within families. RAPGEF5 emerges as a significant gene, along with other neuropsychiatric-related genes. Noteworthy genes like DRD4 and COMT did not show associations, possibly due to the focus on schizophrenic family. While shedding light on this complex relationship, larger studies are needed for robust conclusions and deeper mechanistic insights.

Comparative evaluation of QuantiFERON-TB Gold Plus for diagnosis of latent tuberculosis infection during solid organ transplantation.

Background: The diagnosis of latent tuberculosis infection (LTBI) in solid organ transplantation (SOT) patients under lifelong immunosuppression has profound effects on preoperative and postoperative management. Interferon-gamma release assay (IGRA) is widely used to screen LTBI before or after transplantation. Methods: We evaluated the effect of posttransplantation immunosuppression on IGRA and influencing factors by measuring interval change of QuantiFERON-TB Gold Plus (QFT-Plus) between pretransplantation (pre-QFT-Plus) and posttransplantation (post-QFT-Plus) state in 20 patients who previously had reactive IGRA but not taken LTBI treatment. Results: Eleven (55%) out of 20 pre-QFT-Plus reactive patients became nonreactive state in repeated QFT-Plus (post-QFT-Plus) at 194-413 days (median, 257 days) after transplantation (discordant group). Even in persistently reactive group (concordant group), interferon-gamma (IFN-γ) levels after transplantation were decreased about 34% and 36% of their pretransplantation levels for TB1 and TB2, respectively. The only significant factors that affect interval change of QFT-Plus between pre- and post-SOT status were the concentrations of IFN-γ in pre-QFT-Plus (6.93 vs. 0.44 IU/mL in TB1 and 7.33 vs. 0.71 IU/mL in TB2). Conclusions: The reactivity of QFT-Plus is significantly compromised by immunosuppressive therapy, which increase the risk of false negative, particularly in patients with low level of IGRA reactivity. Therefore, interpretation of IGRA under immunosuppressive treatment require a caution and eventually, more sensitive tuberculosis-specific cytokine markers might be needed.

Creatinine- and cystatin C-based estimated glomerular filtration rate slopes for the prediction of kidney outcome: a comparative retrospective study.

BACKGROUND: Many studies have evaluated the usefulness of creatinine- (eGFRcr) and cystatin C-based estimated glomerular filtration rate (eGFRcys) at specific time points in predicting renal outcome. This study compared the performance of both eGFR changing slopes in identifying patients at high risk of end-stage renal disease (ESRD). METHODS: From 2012 to 2017, patients with more than three simultaneous measurements of serum creatinine and cystatin C for 1 year were identified. Rapid progression was defined as eGFR slope < - 5 mL/min/1.73 m2/year. The primary outcome was progression to ESRD. RESULTS: Overall, 1323 patients were included. The baseline eGFRcr and eGFRcys were 39 (27-48) and 38 (27-50) mL/min/1.73 m2, respectively. Over 2.9 years (range, 2.0-3.8 years) of follow-up, 134 subjects (10%) progressed to ESRD. Both the eGFRcr and eGFRcys slopes were associated with a higher risk of ESRD, independently of baseline eGFR (hazard ratio [HR] = 0.986 [0.982-0.991] and HR = 0.988 [0.983-0.993], respectively; all p <  0.001). The creatinine- and cystatin C-based rapid progressions were associated with increased risk of ESRD (HR = 2.22 [1.57-3.13], HR = 2.03 [1.44-2.86], respectively; all p <  0.001). In the subgroup analyses, the rapid progression group, defined on the basis of creatinine levels (n = 503), showed no association between the eGFRcys slope and ESRD risk (p = 0.31), whereas the eGFRcr slope contributed to further discriminating higher ESRD risk in the subjects with rapid progression based on eGFRcys slopes (n = 463; p = 0.003). CONCLUSIONS: Both eGFR slopes were associated with future ESRD risk. The eGFRcr slope was comparable with the eGFRcys slope in predicting kidney outcome.

Effects of percutaneous angioplasty on kidney function and blood pressure in patients with atherosclerotic renal artery stenosis.

BACKGROUND: Previous randomized controlled trials of revascularization for atherosclerotic renal artery stenosis (ARAS) were not successful. We investigated the effects of percutaneous transluminal angioplasty with stent insertion (PTA/S) on kidney function and blood pressure (BP) control in patients with ARAS. METHODS: From 2000 to 2017, 47 subjects who underwent PTA/S for ARAS were identified. A high-risk group was defined, composed of patients having one or more of the following clinical presentations: pulmonary edema, refractory hypertension, and rapid deterioration of kidney function. Subjects who met the criteria of 'kidney function improvement' or 'hypertension improvement' after PTA/S were classified as responders. RESULTS: Twenty-one (44.7%) subjects were classified into the high-risk group. Two subjects (8.0%) in the low-risk group (n = 25) and 5 subjects (27.8%) in the high-risk group (n = 18) showed improvement in kidney function after PTA/S (P = 0.110). In patients with rapid decline of kidney function, estimated glomerular filtration rate improved from 28 (interquartile range [IQR], 10-45) mL/min/1.73 m2 to 41 (IQR, 16-67) mL/min/1.73 m2 at 4 months after PTA/S, although the difference was not significant (P = 0.084). Regarding BP control, 9 (36.0%) and 14 (77.8%) subjects showed improvement after PTA/S in the low- (n = 25) and high-risk (n = 18) groups, respectively (P = 0.007). In patients with refractory hypertension, the systolic BP dropped from 157 (IQR, 150-164) mmHg to 140 (IQR, 131-148) mmHg at 4 months after PTA/S (P = 0.005). Twenty-five subjects were defined as responders and comprised a significant proportion of the high-risk group (P = 0.004). CONCLUSION: PTA/S might improve BP control and kidney function in patients with ARAS presenting with high-risk clinical features. The optimal application of PTA/S should be based on individual assessment of the clinical significance of renal artery stenosis.

Risk Prediction for Contrast-Induced Nephropathy in Cancer Patients Undergoing Computed Tomography under Preventive Measures.

BACKGROUND: Contrast-induced nephropathy (CIN) is a major cause of acute kidney injury in chronic kidney disease. Many cancer patients have risk factors for CIN and frequently undergo contrast-enhanced computed tomography (CECT). We aimed to develop a risk prediction model for CIN in cancer patients undergoing CECT. METHODS: Between 2009 and 2017, 2,240 cancer patients with estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m2 who underwent CECT with CIN preventive measures were included in a development cohort. Primary outcome was development of CIN, defined as 25% increase in serum creatinine within 2-6 days after contrast exposure. A prediction model was developed using logistic regression analysis. The model was evaluated for prognostic utility in an independent cohort (N = 555). RESULTS: Overall incidence of CIN was 2.5% (55/2,240). In multivariable analysis, eGFR, diabetes mellitus, and serum albumin level were identified as independent predictors of CIN. A prediction model including eGFR, serum albumin level, and diabetes mellitus was developed, and risk scores ranged from 0 to 6 points. The model demonstrated fair discriminative power (C statistic = 0.733, 95% confidence interval [CI] 0.656-0.810) and good calibration (calibration slope 0.867, 95% Cl 0.719-1.015). In the validation cohort, the model also demonstrated fair discriminative power (C statistic = 0.749, 95% CI 0.648-0.849) and good calibration (calibration slope 0.974, 95% CI 0.634-1.315). CONCLUSIONS: The proposed model has good predictive ability for risk of CIN in cancer patients with chronic kidney disease. This model can aid in risk stratification for CIN in patients undergoing CECT.

Arteriovenous graft patency outcomes and prognostic factors.

OBJECTIVES: Arteriovenous graft for hemodialysis shows poorer outcomes than arteriovenous fistula, due to frequent stenosis and thrombosis. We investigated arteriovenous graft patency outcomes and prognostic factors for these outcomes. METHODS: We included a single-center cohort of patients receiving arteriovenous graft for hemodialysis access from 2010 to 2014. Demographics, laboratory data, comorbidities, and medications were collected from medical records. Surgical factors related to graft operation including the type and diameter of connected vessels, graft location, and type of operation (elective or emergency) were also recorded. Outcomes included primary and secondary patency. Survival analysis was conducted using the Kaplan-Meier method; univariate and multivariate analyses were used to evaluate the prognostic factors. RESULTS: Data from 225 grafts were analyzed. During the follow-up period (mean: 583 days, range: 1-1717 days), 138 (61%) grafts required intervention and 46 (20%) permanently failed. Primary patency at one, two, and three years was 42%, 20%, and 16%, respectively. Secondary patency at one, two, and three years was 85%, 72%, and 64%, respectively. Multivariate analysis showed that primary patency was negatively associated with increasing age and location of vessel anastomosis (reference-brachiobrachial anastomosis; brachiobasilic - HR, 0.569; 95% CI, 0.376-0.860; p = 0.007; brachioaxillary anastomosis - HR 0.407; 95% CI, 0.263-0.631; p < 0.0001); secondary patency was positively associated with diastolic blood pressure, serum albumin level, and hemoglobin over 10 g/dL. Adverse events other than stenosis or thrombosis, such as infection/inflammation or pseudoaneurysm were observed in approximately 20% of grafts. CONCLUSIONS: Factors associated with diminished primary arteriovenous graft patency included increased patient age and location of vessel anastomosis (brachiobrachial type compared to brachiobasilic or brachioaxillary type); diminished secondary patency was associated with low diastolic blood pressure, low serum albumin, and hemoglobin level under 10 g/dL. Among these factors, diastolic blood pressure, serum albumin, and hemoglobin level may be modifiable and could improve arteriovenous graft patency outcomes.

Association between diuretics and successful discontinuation of continuous renal replacement therapy in critically ill patients with acute kidney injury.

BACKGROUND: Despite aggressive application of continuous renal replacement therapy (CRRT) in critically ill patients with acute kidney injury (AKI), there is no consensus on diuretic therapy when discontinuation of CRRT is attempted. The effect of diuretics on discontinuation of CRRT in critically ill patients was evaluated. METHODS: This retrospective cohort study enrolled 1176 adult patients who survived for more than 3 days after discontinuing CRRT between 2009 and 2014. Patients were categorized depending on the re-initiation of renal replacement therapy within 3 days after discontinuing CRRT or use of diuretics. Changes in urine output (UO) and renal function after discontinuing CRRT were outcomes. Predictive factors for successful discontinuation of CRRT were also analyzed. RESULTS: The CRRT discontinuation group had a shorter duration of CRRT, more frequent use of diuretics after discontinuing CRRT, and greater UO on the day before CRRT discontinuation [day minus 1 (day - 1)]. The diuretics group had greater increases in UO and serum creatinine elevation after discontinuing CRRT. In the CRRT discontinuation group, continuous infusion of furosemide tended to increase UO more effectively. Multivariable regression analysis identified high day - 1 UO and use of diuretics as significant predictors of successful discontinuation of CRRT. Day - 1 UO of 125 mL/day was the cutoff value for predicting successful discontinuation of CRRT in oliguric patients treated with diuretics following CRRT. CONCLUSIONS: Day - 1 UO and aggressive diuretic therapy were associated with successful CRRT discontinuation. Diuretic therapy may be helpful when attempting CRRT discontinuation in critically ill patients with AKI, by inducing a favorable fluid balance, especially in oliguric patients.

Ten-year observational follow-up of a randomized trial comparing cyclosporine and tacrolimus therapy combined with steroid withdrawal in living-donor renal transplantation.

Although various strategies for steroid withdrawal after transplantation have been attempted, there are few reports of the long-term results of steroid withdrawal regimens in kidney transplantation. Earlier, we reported on a 5-year prospective, randomized, single-center trial comparing the safety and efficacy of cyclosporine (CsA) plus mycophenolate mofetil (MMF) with that of tacrolimus (TAC) plus MMF, when steroids were withdrawn 6 months after kidney transplantation in low-risk patients. We now report the 10-year observational data on the study population. We collected data from the database of the Organ Transplantation Center, Samsung Medical Center for 5 years after completion of the original study (TAC group n = 62; CsA group n = 55). The 10-year patient survival, death-censored graft survival, and acute rejection-free survival did not differ between groups (98% vs 96%; P = 0.49, 78% vs 85%; P = 0.75 and 84% vs 76%; P = 0.14 in the TAC group vs CsA group, respectively). In low-risk patients, there was no difference in long-term patient and graft survival between TAC- and CsA-based late steroid withdrawal regimens that included MMF treatment. More long-term randomized clinical trials are needed to clarify the benefits of late steroid withdrawal in kidney transplantation.

Comparative Evaluation of QuantiFERON-TB Gold In-Tube and QuantiFERON-TB Gold Plus in Diagnosis of Latent Tuberculosis Infection in Immunocompromised Patients.

QuantiFERON-TB Gold Plus (QFT-Plus) is a new-generation QuantiFERON-TB Gold In-Tube (QFT-GIT) assay which has two antigen-coated tubes called TB1, which contains long peptides derived from ESAT-6 and CFP-10, and TB2, which contains the same components as TB1 and additional short peptides which potentially stimulate CD8+ T cells through the presentation of major histocompatibility complex class I. This is the first study to compare QFT-Plus and QFT-GIT for use in the diagnosis of latent tuberculosis infection (LTBI) among immunocompromised patients in the Republic of Korea. Among 317 consecutive patients who underwent screening for LTBI before solid organ or hematopoietic stem cell transplantation and tumor necrosis factor alpha inhibitor treatment, LTBI was identified in 92 (29.0%) and 88 (27.8%) patients by QFT-GIT and QFT-Plus, respectively. The rate of concordance between QFT-GIT and QFT-Plus was 93.7% (κ value, 0.860), and the indeterminate rate (3.2%) was similar between QFT-GIT and QFT-Plus. Of 20 (6.3%) samples with discordant results, 11 (55.0%) and 7 (35.0%) were positive by QFT-GIT alone and QFT-Plus alone, respectively, and 2 (15.0%) were indeterminate by each assay. The interferon gamma level in samples with discordant results ranged from 0.39 to 1.10 IU/ml, except for one sample, in which the gamma interferon level was 2.97 IU/ml only in TB2. Conclusively, there was a high degree of agreement between the results of QFT-GIT and QFT-Plus for the screening of immunocompromised patients for LTBI. The reactivity in TB2 contributed substantially to the difference between QFT-GIT and QFT-Plus, particularly in solid organ transplant candidates. The significance of the discrete responses in TB1 and TB2 of QFT-Plus needs to be explored further by means of an immunological and clinical approach in different patient groups and clinical settings.

First-year GFR slope and long-term renal outcome in IgA nephropathy.

BACKGROUND: IgA nephropathy (IgAN) is the most frequent primary glomerular disease and the leading cause of end-stage renal disease. We investigated clinicopathologic predictors of renal survival in patients with IgAN with a focus on glomerular filtration rate (GFR) decline slope. MATERIALS AND METHODS: We screened all patients with primary IgAN between 1995 and 2012. Renal progression was defined as doubling of serum creatinine. Using serial serum creatinine levels during the first-year, we calculated the GFR decline slopes. Further, we defined patients in the steepest GFR slope quartile as rapid decliners and those in the second steepest GFR slope quartile as slow decliners. Others were defined as nondecliners. RESULTS: Of 214 participants, baseline GFR was 81 (62, 100) mL/min/1.73 m2 , which was not different among the 3 groups. Rapid decliners and slow decliners had higher levels of urinary protein/creatinine ratio (0.88, 0.89 and 0.58 g/gCr, respectively, P < .001). Five-year renal survival was 76% in rapid decliners, 91% in slow decliners and 100% in nondecliners (P < .001, rapid or slow decliners vs nondecliners). After adjustment for clinicopathologic variables, slow decliners were associated with an 8.8-fold higher risk of progression (P = .011), and rapid decliners were associated with a 10.2-fold increased risk of progression (P = .007) compared with nondecliners. CONCLUSIONS: First-year GFR slope was associated with increased risk of renal progression, independent of proteinuria and histologic findings. Further studies are needed to investigate whether early GFR change can identify high-risk patients who benefit from immunosuppressive treatment in IgAN.

Tissue expression of tubular injury markers is associated with renal function decline in diabetic nephropathy.

AIMS: The pathogenesis of diabetic kidney disease (DKD) is complex and multifactorial; increasing evidence suggests that tubular injury and inflammatory process are involved in disease progression. We investigated the potential association of renal expression of tubular injury markers, neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and inflammatory markers, tumor necrosis factor receptor (TNFR) 1 and 2 with renal progression in pathologically proven diabetic nephropathy (DN). METHODS: We identified 122 patients with confirmed DN. After excluding patients with other coexisting renal disease or estimated glomerular filtration rate (eGFR) <30mL/min/1.73m2, 35 patients were included. Annual decline of (GFR decline slope) was calculated using linear regression analysis. Tissue tubular and glomerular expressions of NGAL, KIM-1, TNFR1, and TNFR2 were assessed using immunohistochemistry. RESULTS: Median baseline urinary protein to creatinine ratio (uPCR) was 6.76 (2.18-7.61) mg/mg Cr, median baseline eGFR was 50 (43-66) mL/min per 1.73m2, and median GFR decline slope was 15.6 (4.4-35.1) mL/min per 1.73m2 per year. Positive correlations were observed between tubular expressions of NGAL and KIM-1, and GFR decline slopes (r=0.601, p<0.001; r=0.516, p=0.001, respectively), and between tubular expressions of KIM-1 and uPCR (r=0.596, p<0.001), and between NGAL and interstitial fibrosis and tubular atrophy (IFTA) score (r=0.391, p=0.024). No correlations were found between glomerular or tubular expressions of TNFRs, and clinical parameters including GFR decline slopes. On multivariate analysis, the association between tubular expressions of KIM-1 and GFR decline slopes was dependent on uPCR. Tubular expressions of NGAL were independently associated with GFR decline slopes, with an adjusted coefficient factor of 0.290 (95% confidence interval, 0.009-0.202, p=0.038). CONCLUSIONS: These findings suggest that tubular injury plays a key role in the pathogenesis of DKD in high-risk patients. Further studies are warranted to determine whether tubular injury could be a therapeutic target in DKD.

Independent Contributions of Obstructive Sleep Apnea and the Metabolic Syndrome to the Risk of Chronic Kidney Disease.

STUDY OBJECTIVES: This retrospective study was conducted to evaluate the associations and interactions among obstructive sleep apnea (OSA), chronic kidney disease (CKD), and metabolic syndrome (MS). METHODS: This study included 1,732 subjects (1,482 male and 250 female) in whom OSA was diagnosed by polysomnography. The severity of OSA was defined as mild, moderate, or severe with an apnea-hypopnea index (AHI) score of 5 to < 15, 15 to < 30, and ≥ 30 events/h, respectively. CKD was defined as an estimated glomerular filtration rate < 60 mL/min/1.73 m2 or albuminuria. RESULTS: The prevalence of MS was 29.2% (n = 505). One hundred twenty-nine subjects (7.4%) had CKD. In subjects with MS, CKD prevalence increased progressively with OSA severity: 7.4%, 12.5%, and 15.8% in those with mild, moderate, or severe OSA, respectively (P = .025). Each 10-point increment in AHI score was independently associated with a 1.15-fold higher prevalence of CKD [95% confidence interval (CI), 1.036-1.280; P = .009] after adjustment for all individual components of MS. On the contrary, in those without MS, AHI was not associated with increased odds for CKD [odds ratio, 1.054; 95% CI, 0.930-1.195]. CONCLUSIONS: The independent association between OSA severity and CKD prevalence was observed only in subjects with MS. Further studies are needed to ascertain if OSA contributes to the development of CKD in subjects with MS.

Early, but not late, treatment with human umbilical cord blood-derived mesenchymal stem cells attenuates cisplatin nephrotoxicity through immunomodulation.

Preemptive treatment with mesenchymal stem cells (MSCs) can attenuate cisplatin-induced acute kidney injury (AKI). However, it is uncertain whether MSC treatment after the development of renal dysfunction prevents AKI progression or if MSC immunomodulatory properties contribute to MSC therapy. In this study, human umbilical cord blood (hUCB)-derived MSCs were used to compare the effects and mechanisms of early and late MSC therapy in a murine model. After cisplatin injection into C57BL/6 mice, hUCB-MSCs were administered on day 1 (early treatment) or day 3 (late treatment). With early treatment, cisplatin nephrotoxicity was attenuated as evidenced by decreased blood urea nitrogen (BUN) and reduced apoptosis and tubular injury scores on day 3 Early treatment resulted in downregulation of intrarenal monocyte chemotactic protein-1 and IL-6 expression and upregulation of IL-10 and VEGF expression. Flow cytometric analysis showed similar populations of infiltrated immune cells in both groups; however, regulatory T-cell (Treg) infiltration was 2.5-fold higher in the early treatment group. The role of Tregs was confirmed by the blunted effect of early treatment on renal injury after Treg depletion. In contrast, late treatment (at a time when BUN levels were 2-fold higher than baseline levels) showed no renoprotective effects on day 6 Neither the populations of intrarenal infiltrating immune cells (including Tregs) nor cytokine expression levels were affected by late treatment. Our results suggest that early MSC treatment attenuates renal injury by Treg induction and immunomodulation, whereas a late treatment (i.e., after the development of renal dysfunction) does not prevent AKI progression or alter the intrarenal inflammatory micromilieu.

Comparison of the long-term efficacy and safety of generic Tacrobell with original tacrolimus (Prograf) in kidney transplant recipients.

This study aimed to evaluate the long-term efficacy and safety of a generic tacrolimus (Tacrobell [TCB]) compared to the original tacrolimus (Prograf [PGF]) in kidney transplant recipients. In this retrospective observational study, we analyzed the data from 444 patients who took TCB as a first-line immunosuppressive drug and 245 patients who took PGF. The 5-year graft survival rate was 92% for patients in the PGF group and 97% for patients in the TCB group, respectively. Cox proportional hazards for a one-sided, noninferiority model showed noninferiority (upper confidence interval [CI] limit of the hazard ratio [HR]<1.2) for TCB compared to PGF (HR: 0.58; 95% CI: 0-1.14). The 5-year patient survival rate was 96% for patients in the PGF group and 97% for patients in the TCB group. Cox proportional hazards for a one-sided, noninferiority model showed noninferiority (upper confidence interval limit of the HR<2.0) for TCB compared to PGF (HR: 0.83; 95% CI: 0-1.95). The 5-year acute rejection-free graft survival rate was not significantly different between the groups (TCB 67%, PGF 68.8%; P=0.6286). The incidence of adverse events including adverse cardiovascular or cerebrovascular events, malignancies, new-onset diabetes after transplantation, and infection events did not differ significantly between the two groups. We conclude that TCB is a comparable alternative to the original tacrolimus as a first-line immunosuppressive drug. Producers of generics should support further study of their products after approval to assure physicians of their efficacy and safety.

Hydrochlorothiazide does not increase furosemide's effects in end-stage renal disease.

Diuretic therapy for the treatment of edema in patients with end-stage renal disease (ESRD) is unsatisfactory, and a combination of thiazide and loop diuretics may produce better clinical effects. To evaluate the influence of thiazide on loop diuretic therapy for ESRD, we performed a crossover study of furosemide versus hydrochlorothiazide plus furosemide treatment. The diuretic effects of furosemide (160 mg i.v.) alone versus a combination of hydrochlorothiazide (100 mg p.o.) and furosemide were studied in ten ESRD patients with proteinuria greater than 1 g/day. The diuretic effects were compared for 24 h urine volume and electrolyte excretion. To detect the influence of thiazide that may have been obscured in the widely dispersed data, pharmacodynamic analysis of urine furosemide excretion rate versus fractional excretion of sodium (FeNa) was also performed using mixed-effect modeling. Combination therapy was not significantly different from furosemide monotherapy in terms of 24 h urine volume, chloride, or sodium excretion. Hydrochlorothiazide was not a significant covariate in the furosemide effect for the pharmacodynamic model. In patients with ESRD and severe proteinuria (>1,000 mg/day), the combination of hydrochlorothiazide with furosemide therapy did not increase the diuretic effect of furosemide.

The incidence and locational predilection of metachronous tumors after endoscopic resection of high-grade dysplasia and early gastric cancer.

BACKGROUND: The incidence of metachronous lesions after endoscopic resection (ER) of high-grade dysplasia (HGD) has not been evaluated, and optimal surveillance strategy remains vague. This study aimed to evaluate the incidence and characteristics of metachronous tumors including HGD and early gastric cancer (EGC) arising after ER. PATIENTS: The medical records of 2779 patients with 2981 lesions (445 patients with HGD and 2334 patients with EGC) who underwent ER and surveillance endoscopy at Asan Medical Center between April 1999 and December 2011 were retrospectively reviewed, and clinicopathological features of metachronous tumors were analyzed. RESULTS: Ninety-six metachronous lesions (17 HGD and 79 EGC) occurred in 92 patients during median 42 months of follow-up period (range 26-58 months). The 5-year and 10-year overall cumulative incidences of metachronous tumors were 4.6 and 10.5 %, respectively, and were on steady rise up to 10 years. The 5- and 10-year cumulative incidences of metachronous lesions were 4.1 and 8.4 % in HGD group and 4.7 and 11.3 % in EGC group (P = 0.578), respectively. The size of metachronous tumors was significantly smaller than initial lesion (2.3 vs. 1.9 cm, P = 0.039). Lower third of the stomach was most frequent site for both initial and metachronous lesions (77.1 and 70.8 %, respectively) and age was the significant predicting factor for metachronous tumors. CONCLUSIONS: Cumulative incidence of metachronous tumors after ER of HGD was comparable to the incidence after ER of EGC. Surveillance endoscopy can be considered at least for 10 years, with special attention on the lower third of the stomach.

Diagnostic performances of M-protein tests according to the clinical presentations of kidney disease.

BACKGROUND: Screening for monoclonal immunoglobulin (MIg) is critical in patients with kidney disease. METHODS: We identified 943 subjects who underwent kidney biopsy and at least one of monoclonal (M)-protein tests (serum and urine electrophoresis [EP], serum and urine immunofixation [IF], and serum free light chain [FLC] ratio). The sensitivities of several combinations of the 5 tests were examined by clinical presentations of kidney disease. RESULTS: The sensitivities of serum EP, urine EP, and the serum FLC ratio were 65%, 68%, and 71%, respectively, which were lower than those of serum IF (79%) and urine IF (87%) to detect MIg. In the nephrotic syndrome (NS) group, the panel including serum IF, urine IF, and the serum FLC ratio exhibited 100% sensitivity to identify MIg in patients with multiple myeloma (MM) or with monoclonal gammopathy of renal significance (MGRS). In subjects without NS, the panel of serum EP and serum FLC ratio detected MIg in all cases of MM, and the serum IF plus serum FLC ratio detected MIg in all cases of MGRS. CONCLUSION: This study demonstrated that the sensitivity of screening panels differed by the presenting features of kidney disease. The M-protein tests had lower sensitivity for detection of MIg in subjects with NS compared to those with other clinical presentation.

Risk factors for renal impairment revealed after unilateral adrenalectomy in patients with primary aldosteronism.

Primary aldosteronism (PA) may induce significant decline of renal function and structural damage of kidney. However, it is difficult to evaluate accurate renal function in patients with PA, because glomerular hyperfiltration and aldosterone escape can conceal renal impairment. In this retrospective cohort study, we compared changes in renal function after unilateral adrenalectomy between patients with PA and patients with other adrenal diseases. Risk factors associated with postoperative renal impairment in patients with PA were analyzed.A total of 558 patients who received unilateral adrenalectomy between January 2002 and June 2013 were included: 136 patients with PA and 422 patients with other adrenal diseases (control). Postoperative serial changes in estimated glomerular filtration rate (eGFR) were analyzed in both groups. Multivariate analyses were performed to identify risk factors of renal impairment after adrenalectomy in all patients and the PA group. Postoperative renal impairment was defined as postoperative eGFR decline of >25% from preoperative eGFR. Chronic kidney disease (CKD) was defined as an eGFR <60 mL/min/1.73 m.There were no differences in preoperative eGFR between groups. The PA group showed a significant decrease in eGFR 3 days, 2 weeks, and 6 months after surgery compared to the control group. The PA group showed significant improvement of hypertension after surgery. In the PA group, 53 (39.0%) patients showed postoperative renal impairment. Multivariate regression analysis identified long-standing hypertension, low body mass index, low serum potassium, and high preoperative eGFR as risk factors for postoperative renal impairment. Among the 89 patients with preoperative eGFR ≥60 mL/min/1.73 m, 29 (32.6%) patients developed CKD postoperatively. Age, low serum potassium, low preoperative eGFR, and high serum cholesterol or uric acid were associated with the postoperative CKD development.Our study demonstrates that patients with PA with old age, low serum potassium, long-standing hypertension, and high serum uric acid or cholesterol are at risk of renal impairment after surgical treatment. High preoperative eGFR was also a risk factor for postoperative renal impairment, whereas low preoperative eGFR was a risk factor for postoperative CKD. Close monitoring of renal function and adequate management are required for patients with these risk factors.

The effects of cytotoxic therapy in progressive IgA nephropathy.

BACKGROUND: IgA nephropathy (IgAN) is not always benign, and some patients at high risk of end-stage renal disease (ESRD) experience a rapid decline in renal function. This study retrospectively examined the beneficial effects of cytotoxic therapy. METHODS: We identified 102 patients with progressive IgAN despite optimal conservative management. Of these, 31 who received cytotoxic therapy and 55 who were managed conservatively were included. RESULTS: Median eGFR and urinary protein-to-creatinine ratio (uPCR) at baseline did not differ between the groups (p = 0.475 and 0.259, respectively). Median GFR slope was also similar (p = 0.896). Cumulative renal survival was better in the cytotoxic therapy group than in the control group (p = 0.009). Cytotoxic therapy was associated with lower risk of progression to ESRD, independent of eGFR, uPCR, GFR slope and kidney histologic findings (HR 0.13, 95% CI 0.03-0.66). In the cytotoxic therapy group, the median GFR slope decreased from -7.8 (-10.5, -5.0) mL/min/1.73 m(2) per year to -3.4 (-5.1, -1.8) mL/min/1.73 m(2) per year after treatment (p < 0.001). Mortality was not observed, but infection requiring hospitalization occurred at similar rates in both groups (p = 0.886). CONCLUSIONS: Cytotoxic therapy attenuated the rate of GFR decline and was associated with a favorable renal outcome in patients with progressive IgAN.

Warfarin skin necrosis mimicking calciphylaxis in a patient with secondary hyperparathyroidism undergoing peritoneal dialysis.

Warfarin skin necrosis (WSN) is an infrequent complication of warfarin treatment and is characterized by painful ulcerative skin lesions that appear a few days after the start of warfarin treatment. Calciphylaxis also appears as painful skin lesions caused by tissue injury resulting from localized ischemia caused by calcification of small- to medium-sized vessels in patients with end-stage renal disease. We report on a patient who presented with painful skin ulcers on the lower extremities after the administration of warfarin after a valve operation. Calciphylaxis was considered first because of the host factors; eventually, the skin lesions were diagnosed as WSN by biopsy. The skin lesions improved after warfarin discontinuation and short-term steroid therapy. Most patients with end-stage renal disease have some form of cardiovascular disease and some require temporary or continual warfarin treatment. It is important to differentiate between WSN and calciphylaxis in patients with painful skin lesions.