Usefulness of mid-week hemoglobin measurement for anemia management in patients undergoing hemodialysis: a retrospective cohort study.

BACKGROUND: Short-term hemoglobin (Hb) variability related to volume status is observed in chronic kidney disease (CKD) patients receiving hemodialysis (HD). Given the lack of studies regarding outcomes according to the day of Hb sampling, the existing guidelines do not strongly recommend regarding measurement timing. Pre-dialysis mid-week sampling (Wednesday and Thursday) is preferable to minimize short-term Hb variability, although numerous HD centers perform early-week sampling (Monday and Tuesday). The different measurement days may influence the prescribed dose of erythropoiesis-stimulating agent (ESA) and related patient outcomes. We investigated changes in Hb levels and ESA doses according to the Hb measurement day among HD patients. METHODS: Starting September 2013, the day for pre-dialysis Hb measurement at the Asan Medical Center was changed from early-week days to mid-week days. This single-center retrospective study evaluated medical records of 92 patients who received maintenance HD between September 2012 and August 2014. RESULTS: There was no significant difference in the mean Hb levels between early-week days and mid-week days (10.71 ± 0.06 g/dL vs. 10.78 ± 0.47 g/dL, p = 0.105). However, the mean doses of darbepoetin-α on early-week days were higher than those on mid-week days (175.4 ± 72.5 µg/month vs. 163.7 ± 83.6 µg/month, p = 0.022). The mean doses of intravenous iron hydroxide sucrose for early-week measurements were also higher than those for mid-week measurements (623.0 ± 489.0 mg/year vs. 447.0 ± 505.2 mg/year, p = 0.001). The mean interdialytic weight gains were 2.81 ± 0.82 kg on early-week days and 1.99 ± 0.61 kg on mid-week days (p < 0.001). CONCLUSIONS: Compared with early-week measurements, mid-week pre-dialysis Hb measurements were significantly associated with lower ESA doses without a change in Hb levels.

Desmopressin improves platelet function in uremic patients taking antiplatelet agents who require emergent invasive procedures.

Uremia is associated with platelet dysfunction and can cause a bleeding tendency resulting in a major bleeding event after an invasive procedure or surgery that may be aggravated by antiplatelet agents. We prospectively investigated the potential of desmopressin to improve platelet dysfunction and to lower bleeding risk after emergent invasive procedures in uremic patients taking antiplatelet drugs. Twenty-three patients were enrolled with a mean age of 60.2 ± 11.7 years. Baseline blood urea nitrogen and creatinine were 70.5 ± 29.4 and 10.02 ± 4.52 mg/dL, respectively. Twenty-one patients took aspirin. All patients were infused with desmopressin before their invasive procedures, which were a central catheter insertion for emergent hemodialysis in 13 patients, percutaneous nephrostomy in 7 patients, and angiography through arm or leg vessels in 3 patients. After desmopressin infusion, both the hematocrit and platelet count were slightly decreased without changes in prothrombin time or activated partial thrombin time. Collagen/epinephrine-closure time was significantly shortened from 252.7 ± 40.7 to 144.6 ± 51.0 s (p < 0.001). There were minimal bleeding in 20 patients and mild bleeding in 3 patients. None experienced severe bleeding event or required additional intervention for bleeding control. There were no adverse events including the decrease of serum sodium concentration. In conclusion, a single infusion of desmopressin before invasive procedures in uremic patients on antiplatelet drugs appeared to be well tolerated and improved platelet dysfunction measured by collagen/epinephrine-closure time.

Prophylactic effect of erythropoietin injection to prevent acute mountain sickness: an open-label randomized controlled trial.

This study was performed to evaluate whether increasing hemoglobin before ascent by prophylactic erythropoietin injections prevents acute mountain sickness (AMS). This open-label, randomized, controlled trial involved 39 healthy volunteers with hemoglobin ≤ 15.5 g/dL who were divided randomly into erythropoietin (n=20) and control (n=19) groups. Epoetin alpha 10,000 IU injections were given weekly for four consecutive weeks. On day 1, and 7 days after the last injection (day 29), oxygen saturation (SaO2), and hemoglobin were measured. The subjects departed Seoul on day 30 and arrived at Annapurna base camp (ABC, 4,130 m) on day 34. AMS was diagnosed when headache and Lake Louise score (LLS) of ≥ 3 were present. Immediate descent criteria followed US Army recommendations. Two groups differ in hemoglobin levels on day 29 (15.4 ± 1.1 vs 14.2 ± 1.0 g/dL, P=0.001). At ABC, erythropoietin group had a significantly lower mean LLS, AMS incidence, and number of subjects who met immediate descent criteria. Multiple logistic regression analysis showed that SaO2<87% and control group, but not hemoglobin<15.0 g/dL, independently predicted satisfaction of immediate descent criteria. Erythropoietin-related adverse effects were not observed. In conclusion, erythropoietin may be an effective prophylaxis for AMS.(Clinical Trial Registry Number; NCT 01665781).

Treatment outcomes for idiopathic sudden sensorineural hearing loss in dialysis patients.

Idiopathic sudden sensorineural hearing loss (ISSNHL) is challenging for both nephrologists and otolaryngologists treating patients undergoing dialysis. This single-center, retrospective, observational study investigated the treatment outcomes of patients with ISSNHL undergoing dialysis, enrolling 700 patients (47 undergoing and 653 not undergoing dialysis) diagnosed with ISSNHL between January 2005 and December 2021 at Asan Medical Center, Republic of Korea. To balance pre-existing clinical characteristics, 1:5 propensity score matching (PSM) was performed with the patients who were not undergoing dialysis. Treatment included high-dose systemic steroid therapy or intra-tympanic steroid injections. The pure tone average of the groups was compared before and 2 weeks and 2 months after treatment. The hearing-improvement degree was evaluated using Siegel's criteria. Before PSM, age, prevalence of diabetes or hypertension, initial hearing threshold at each frequency level (0.5, 1, 2, and 4 kHz), and treatment strategies exhibited significant between-group differences. However, in the PS-matched cohort, none of the confounders showed significant between-group differences. Two months after steroid treatment, the non-dialysis patient group demonstrated significantly higher average improvement in pure tone audiometry (P = 0.029) and greater percentage of complete response according to Siegel's criteria. This study suggests that treatment outcomes for ISSNHL are significantly poorer for patients undergoing than for those not undergoing dialysis.

AMP-activated protein kinase inhibits TGF-ß-, angiotensin II-, aldosterone-, high glucose-, and albumin-induced epithelial-mesenchymal transition.

The epithelial-mesenchymal transition (EMT) is a novel mechanism that promotes renal fibrosis. Transforming growth factor-ß (TGF-ß), angiotensin II, aldosterone, high glucose, and urinary albumin are well-known causes of EMT and renal fibrosis. We examined whether and how activation of AMP-activated protein kinase (AMPK) suppressed EMT induced by the above agents in tubular epithelial cells. All experiments were performed using HK-2 cells. Protein expression was measured by Western blot analysis. Intracellular reactive oxygen species (ROS) were analyzed by flow cytometry. Exposure of tubular cells to TGF-ß (10 ng/ml), angiotensin II (1 µM), aldosterone (100 nM), high glucose (30 mM), and albumin (5 mg/ml) for 5 days induced EMT, as shown by upregulation of α-smooth muscle actin and downregulation of E-cadherin. ROS and NADPH oxidase 4 (Nox4) expression were increased, and antioxidants such as tiron and N-acetylcysteine inhibited EMT induction. Metformin (the best known clinical activator of AMPK) suppressed EMT induction through inhibition of ROS via induction of heme oxygenase-1 and endogenous antioxidant thioredoxin. An AMPK inhibitor (compound C) and AMPK small interfering RNA blocked the effect of metformin, and another AMPK activator [5-aminoimidazole-4-carboxamide-1ß riboside (AICAR)] exerted the same effects as metformin. In conclusion, AMPK activation might be beneficial in attenuating the tubulointerstitial fibrosis induced by TGF-ß, angiotensin II, aldosterone, high glucose, and urinary albumin.

Activation of AMP-activated protein kinase inhibits albumin-induced endoplasmic reticulum stress and apoptosis through inhibition of reactive oxygen species.

BACKGROUND: Endoplasmic reticulum (ER) stress induced by urinary albumin plays an important role in tubulointerstitial injury. We have shown that albumin-induced ER stress is regulated through reactive oxygen species (ROS)-c-Src kinase-mTOR signaling pathways. We postulated that peroxisome proliferator-activated receptor-γ (PPAR-γ) might also act as an upstream signaling molecule between c-Src kinase and mTOR. It has been suggested that AMP-activated protein kinase (AMPK) is involved in attenuation of ER stress. We examined whether and how activation of AMPK suppressed the albumin-induced ER stress and apoptosis in tubular epithelial cells. METHOD: HK-2 cells, a proximal tubular cell line, were used. Protein expressions were measured by Western blot analysis. Intracellular ROS and apoptosis were analyzed by flow cytometry. RESULTS: Albumin-induced PPAR-γ expression and PPAR-γ inhibitor (GW9662) suppressed the albumin-induced ER stress. c-Src kinase inhibitor and GW9662 reduced the albumin-induced PPAR-γ and mTOR, respectively. Metformin (the best known clinical activator of AMPK) and another AMPK activator (AICAR) suppressed the albumin-induced ER stress via inhibition of ROS through induction of endogenous antioxidant thioredoxin. AMPK inhibitor blocked the effect of metformin and AICAR. Our in vivo animal study showed that metformin reduced the renal cortical expression of ER stress protein (GRP78) in protein-overload proteinuria rats. Metformin also reduced the caspase 3-dependent apoptosis induced by albumin. CONCLUSION: PPAR-γ was involved in albumin-induced ER stress as an upstream signaling molecule between c-Src kinase and mTOR. AMPK activation might be beneficial in attenuating the tubulointerstitial injury induced by albumin.

The efficacy of steroid pulse therapy in patients with IgA nephropathy.

BACKGROUND: The efficacy and proper doses of steroid pulse therapy in patients with immunoglobulin A nephropathy (IgAN) have not been established. We therefore investigated the effects of methylprednisolone (MP) pulse therapy in patients with histologically active IgAN and established renal impairment at the time of treatment. METHODS: We assessed 22 patients (8 males, 14 females) with established renal impairment (Stage 3, 4 or 5 CKD; median eGFR, 34.05 ml/min/1.73 m2) and active IgAN (median histological Grade 3). All patients had been maintained on an angiotensin receptor blocker or an angiotensinconverting enzyme inhibitor. Patients were treated with 500 mg intravenous MP every 2 weeks for 6 months to improve or stabilize renal function. The efficacy of MP pulse therapy was analyzed by comparing the slopes of the eGFR (ml/min/1.73 m2) and log transformed urine albumin/creatinine ratios (mg/g) before, during, and after treatment using linear regression coefficients. RESULTS: All patients completed the planned 6 months of MP pulse therapy. Linear regression analysis showed improvements in the monthly decline of eGFR in 16 of 22 patients (73%) after treatment. The rate of eGFR decline in the before treatment period differed significantly from that in the after treatment period (-0.931 ± 0.871 vs 0.141 ± 0.998, p = 0.007). Patients with initial eGFR ≥ 30 ml/min/1.73 m2 showed significantly improved 10-month dialysisfree renal survival after MP pulse therapy (p = 0.040). In contrast, there was no improvement in urinary albumin to creatinine ratio (p = NS). MP pulse therapy was well tolerated, except for one patient with facial flushing and palpitation. There were no other serious adverse events during the study period. CONCLUSIONS: MP 500 mg every 2 weeks for 6 months was safe and effective in patients with IgAN and preexisting renal dysfunction.

Assessment of the influence of severe renal impairment on the pharmacokinetics of mirodenafil in Korean male volunteers.

OBJECTIVE: To evaluate and compare the pharmacokinetics and tolerability of a single oral dose of mirodenafil in volunteer patients with severe renal impairment and healthy volunteers. METHODS AND MATERIALS: This open-label, single-dose, parallel group clinical study enrolled a total 12 volunteers (6 healthy volunteers and 6 volunteer patients with severe renal impairment). Each volunteer was orally administered 50 mg mirodenafil and serial blood samples were obtained after drug administration to determine the plasma concentration of mirodenafil using LC-MS/MS. The measured individual plasma concentrations were used to calculate the pharmacokinetic parameters using noncompartmental methods. Tolerability was also assessed using measurements of vital signs, clinical chemistry tests, and interviews. RESULTS: All of the volunteers completed the study with no serious adverse events (AEs). A total of 4 AEs were reported, but all were of mild or moderate intensity and not considered to be related to the study drug. The geometric mean (95% CI) of the terminal half-life (t1/2ß) and the apparent clearance (CL/F) values of mirodenafil were 2.2 (1.4 - 3.4) h and 127.2 (95.1 - 170.2) l/h in the volunteer patients, and 3.0 (2.1 - 4.4) h and 136.1 (74.4 - 249.2) l/h in the healthy volunteers, respectively. The geometric mean of the AUC0-t of the volunteer patients was 8% higher and the geometric mean for clearance was 7% lower compared with the healthy volunteers. However, the geometric mean of the Cmax of the volunteer patients was 38% higher than that of the healthy volunteers. CONCLUSIONS: A single oral 50-mg dose of mirodenafil was well tolerated. Exposure (AUC0-t) to mirodenafil was similar in both healthy volunteers and volunteer patients with severe renal impairment and healthy volunteers.

Does stage III chronic kidney disease always progress to end-stage renal disease? A ten-year follow-up study.

OBJECTIVE: Clinically, it may be appropriate to subdivide patients with stage 3 chronic kidney disease (CKD) into two subgroups, as they show different risks for kidney outcomes. This study evaluated the proportion of patients with stage 3 CKD who progressed to stage 4 or 5 CKD over 10 years and independent predictors of progression of renal dysfunction. It sought to validate whether stage 3 CKD patients should be subdivided. MATERIAL AND METHODS: This retrospective cohort study enrolled 347 stage 3 CKD patients between January 1997 and December 1999, who were followed up through June 2010. The baseline clinical characteristics and outcomes were compared in patients with stage 3A [45

Percutaneous pericardial catheter drainage for symptomatic uremic pericardial effusions with narrow safety margins.

BACKGROUND: Percutaneous pericardial catheter drainage (PCD) for pericardial effusion is generally known to be limited by the high risk associated with effusions that are less than 10 mm thick. The objective was to report cases who underwent percutaneous PCD for symptomatic uremic pericardial effusions, which were less than 10 mm thick after cardiologist declined to perform the PCDs because of the narrow safety margins. MATERIALS AND METHODS: Thirteen consecutive cases (11 patients) (median age, 56 years, range, 31-83) with symptomatic uremic pericardial effusion (thickness <10 mm) affecting the pericardial space anterior to the right ventricle underwent ultrasound- and fluoroscopy-guided percutaneous PCD between September 2015 and April 2022. Information regarding the clinical criteria, echocardiographic features, PCD details, nature of effusion, and outcomes, including success and complications were retrospectively evaluated. RESULTS: Pigtail catheter (8.5-Fr) insertion was successful for all patients, with a median procedure time of 7 minutes (range 4~12) without procedure-related complications. The median amount of drainage on the day of PCD was 700 mL (range, 250-1100). The median duration of catheter indwelling was 5 days (range, 1~32). In one case, the catheter was removed after 1 day due to chest pain. For all patients, pericardial effusion evacuation was achieved with relief of associated symptoms, representing 100% clinical success. CONCLUSION: Percutaneous PCD may be safely performed for patients with symptomatic uremic pericardial effusions and narrow safety margins of less than 10 mm.

No effect of desmopressin administration before kidney biopsy on the risk of major post-biopsy bleeding.

BACKGROUND/AIMS: The most important complication of kidney biopsy is bleeding, and it is unclear whether desmopressin is effective in preventing it. Thus, the study was conducted to compare post-biopsy bleeding with or without desmopressin prescription prior to percutaneous kidney biopsy. METHODS: In this single-centered, retrospective, and observational study, 3,018 adult patients who underwent kidney biopsy between January 1, 2003 and March 31, 2019 at our institute were recruited. Of these, 776 patients received desmopressin. To compare the differences in major bleeding events between patients administered and not administered with desmopressin, propensity score matching was performed. RESULTS: Before propensity score (PS) matching, it was observed that patients in the desmopressin group were significantly older (p<0.001) and had a higher blood pressure (p<0.001), higher serum creatinine (p<0.001), lower hemoglobin levels (p<0.001), and lower platelet counts (p=0.001) than those in the no-desmopressin group. Furthermore, the incidence of renal artery embolization was not significantly different between the two groups (p=0.077); however, blood transfusions occurred significantly more frequently in the desmopressin group (p<0.001). A comparison of the two groups after PS matching did not reveal any differences in the incidence of renal artery embolization (p=0.341), blood transfusion (p=0.579), and total major bleeding events (p=0.442). Furthermore, there was no difference in the incidence of perinephric hematoma on computed tomography or ultrasound (p=0.120). CONCLUSIONS: We do not recommend desmopressin administration before kidney biopsy.

No difference in follow-up estimated glomerular filtration rate between hypertensive and matched nonhypertensive kidney donors.

BACKGROUND: According to current guidelines, kidney donor candidates with controlled hypertension using 1 or 2 antihypertensive drugs may be considered as donor. However, this recommendation is based on the study that antihypertensive drug was initiated in mainly "after donor registration" and this may be white-coat hypertension because of donation-related anxiety. We compared the follow-up eGFR between kidney donors with preexisting hypertension and matched nonhypertensive donors. METHODS: This single-center retrospective study classified 97 living hypertensive donors previously receiving antihypertensive drugs into two groups: 1 drug group (61 donors) and 2 drugs group (36 donors). We compared the follow-up eGFR between each donor previously receiving antihypertensive drugs and three matched nonhypertensive donors in terms of age, sex, and follow-up duration. RESULTS: At a mean (range) of 51 months (12-214) in the 1 drug group, and 54 months (12-175) in the 2 drugs group after donation, there was no significant difference in follow-up eGFR between hypertensive donors previously receiving antihypertensive drugs and matched controls in each group and in total donors. There was no difference in the incidence of the patients with follow-up eGFR<45mL/min/m2 in each group and their matched controls. Multiple linear regression analysis showed that baseline eGFR was the only independent predictor for the final follow-up eGFR in the total donors. CONCLUSION: Our results support the current guidelines that donor candidates with controlled hypertension using 1 or 2 antihypertensive drugs may be considered as donors, and may increase the strength of this recommendation.

Albumin-induced epithelial-mesenchymal transition and ER stress are regulated through a common ROS-c-Src kinase-mTOR pathway: effect of imatinib mesylate.

The epithelial-mesenchymal transition (EMT) and endoplasmic reticulum (ER) stress induced by urinary protein, particularly albumin, play an important role in tubulointerstitial injury. However, signaling pathways regulating both albumin-induced EMT and ER stress are not precisely known. We postulated that reactive oxygen species (ROS), c-Src kinase, and mammalian target of rapamysin (mTOR) would act as upstream signaling molecules. We further examined the effect of imatinib mesylate on these processes. All experiments were performed using HK-2 cells, a human proximal tubular cell line. Protein and mRNA expression were measured by Western blot analysis and real-time PCR, respectively. Exposure of tubular cells to albumin (5 mg/ml) for up to 5 days induced EMT in a time-dependent manner, as shown by conversion to the spindle-like morphology, loss of E-cadherin protein, and upregulation of α-smooth muscle actin mRNA and protein. Albumin also induced ER stress as evidenced by phosphorylation of eukaryotic translation initiation factor-2α and increased expression of GRP78 mRNA and protein. Albumin induced ROS, c-Src kinase, and mTOR as well. Antioxidants, c-Src kinase inhibitor (PP2), and mTOR inhibitor (rapamycin) suppressed the albumin-induced EMT and ER stress. Antioxidants and PP2 inhibited the albumin-induced c-Src kinase and mTOR, respectively. Imatinib suppressed the albumin-induced EMT and ER stress via inhibition of ROS and c-Src kinase. Imatinib also inhibited the albumin-induced mRNA expression of MCP-1, VCAM-1, transforming growth factor (TGF)-ß1, and collagen I (α1). In conclusion, the ROS-c-Src kinase-mTOR pathway played a central role in the signaling pathway that linked albumin to EMT and ER stress. Imatinib might be beneficial in attenuating the albumin-induced tubular injury.

Statin therapy is associated with improved survival in incident peritoneal dialysis patients: propensity-matched comparison.

BACKGROUND: Patients with end-stage renal disease (ESRD) have a greatly increased risk of premature cardiovascular disease. Peritoneal dialysis (PD) patients have more atherogenic lipid profiles than haemodialysis patients. In this retrospective cohort study, we evaluated whether statin use is associated with improved mortality in incident PD patients. METHODS: The study population included consecutive new PD patients (≥18 years old) from seven PD centres in Korea, between January 2003 and December 2008. The clinical outcome was mortality. A propensity score (PS) comprising demographic, clinical and laboratory variables was used to select a 1:1 matched cohort. RESULTS: Statins were prescribed for 37.8% of incident PD patients. Cumulative survival probabilities for statin user versus non-user were 87 versus 80% and 76 versus 69% at 3 and 5 years, respectively (P = 0.01). Statin prescription was associated with a 41% lower adjusted hazard ratio (HR) of death in the unmatched cohort [95% confidence interval (CI) = 0.42-0.82; P = 0.002]. The protective effect of statins was also observed in a subgroup analysis of patients with diabetic ESRD (HR = 0.53, 95% CI = 0.36-0.80; P = 0.002). After PS matching, the use of statins was also associated with improved survival (HR = 0.55, 95% CI = 0.38-0.79; P = 0.001) in incident PD patients. CONCLUSIONS: The use of statins was associated with a reduced risk of all-cause mortality. This association was independent of a history of cardiovascular disease or total cholesterol level. Future randomized clinical trials are warranted to confirm the beneficial effect of statin on PD patients.

No effect of desmopressin administration before kidney biopsy on the risk of major post-biopsy bleeding.

BACKGROUND/AIMS: The most important complication of kidney biopsy is bleeding, and it is unclear whether desmopressin is effective in preventing it. Thus, the study was conducted to compare post-biopsy bleeding with or without desmopressin prescription prior to percutaneous kidney biopsy. METHODS: In this single-centered, retrospective, and observational study, 3,018 adult patients who underwent kidney biopsy between January 1, 2003 and March 31, 2019 at our institute were recruited. Of these, 776 patients received desmopressin. To compare the differences in major bleeding events between patients administered and not administered with desmopressin, propensity score matching was performed. RESULTS: Before propensity score (PS) matching, it was observed that patients in the desmopressin group were significantly older (p<0.001) and had a higher blood pressure (p<0.001), higher serum creatinine (p<0.001), lower hemoglobin levels (p<0.001), and lower platelet counts (p=0.001) than those in the no-desmopressin group. Furthermore, the incidence of renal artery embolization was not significantly different between the two groups (p=0.077); however, blood transfusions occurred significantly more frequently in the desmopressin group (p<0.001). A comparison of the two groups after PS matching did not reveal any differences in the incidence of renal artery embolization (p=0.341), blood transfusion (p=0.579), and total major bleeding events (p=0.442). Furthermore, there was no difference in the incidence of perinephric hematoma on computed tomography or ultrasound (p=0.120). CONCLUSIONS: We do not recommend desmopressin administration before kidney biopsy.

Transrenal Hemodialysis Catheter Insertion and Replacement in Patients with Upper Extremity Central Venous Access Exhaustion.

PURPOSE: Patients undergoing long-term hemodialysis may suffer upper extremity central venous access failure and require an alternative route. This study aimed to evaluate the safety and efficacy of transrenal hemodialysis catheter insertion/replacement in patients with upper extremity central venous access failure. MATERIALS AND METHODS: A multicenter retrospective cohort study was made of transrenal hemodialysis catheter insertion/replacement performed between 2014 and 2020. The history of renal replacement therapy and central venous catheters and the technical details of transrenal hemodialysis catheter insertion/replacement, patency, removal and complications were obtained for all patients. RESULTS: Six insertion and four replacement procedures involving transrenal hemodialysis catheters were evaluated in six patients (M:F = 3:3; median age, 49.5 years). Percutaneous transrenal (right:left = 1:5) hemodialysis catheter insertion was technically successful without complication in all six patients. In two patients, the tract was not lost because the safety guidewire was still in place, so no second puncture was required. The mean procedure time was 33.0 ± 9.2 min. The mean primary patency duration was 107.3 ± 70.9 days. During the mean follow-up duration of 141.2 ± 137.1 days, four hemodialysis catheter replacement procedures were successfully performed for catheter malfunction (n = 2) and dislodgement (n = 2). Catheter removal was successfully performed in four patients after confirming normal coagulation, followed by subsequent renal replacement therapy. CONCLUSION: Percutaneous insertion/replacement of transrenal hemodialysis catheters is feasible, safe, and effective when upper extremity central venous access is exhausted, and the catheters can be maintained for a reasonable period of time. LEVEL OF EVIDENCE: Level 4, Case Series.

Renal Recovery After Liver Transplantation Alone in Patients With Liver Cirrhosis and Severe Chronic Kidney Disease With Normal Kidney Size.

BACKGROUND: Most guidelines recommend simultaneous liver-kidney transplantation (SLKT) in patients with liver cirrhosis (LC) and severe chronic kidney disease (CKD) over liver transplantation alone (LTA). CKD, however, is not irreversible. This study evaluates the reversibility of kidney disease after LTA based on kidney size. MATERIALS AND METHODS: In this single-center retrospective study, we classified 90 patients with LC and severe CKD into 3 groups: the normal kidney (NK)-LTA group (n=39), small kidney (SK)-LTA group (both kidneys <9 cm at the time of LTA, n=40), and SK-SLKT group (n=11). RESULTS: The NK-LTA group had a lower percentage of hepatocellular carcinoma and a higher pre-liver transplantation (LT) estimated glomerular filtration rate. This group, however, was older, received livers from a higher percentage of deceased donors, and had a higher Child-Pugh score. Renal recovery, defined as the return of creatinine to their baseline, or a persistent change from baseline but not persistent (≥3 months) need for renal replacement therapy after LT, was found in 79% in the NK-LTA group, which was higher than 7.5% in the SK-LTA group. Renal and patient survival was found in 56% of the NK-LTA group, which was higher than 2.5% of the SK-LTA group. CONCLUSIONS: There is a high percentage of renal recovery in the NK-LTA group, and accordingly, this does not justify SLKT, since this would result in a "waste" of kidneys. Therefore, KT after LT is recommended over SLKT for the LC patients with NK size.

Myoglobin induces vascular cell adhesion molecule-1 expression through c-Src kinase-activator protein-1/nuclear factor-kappaB pathways.

BACKGROUND/AIMS: It is not clear whether a sublethal dose of myoglobin induces some pathophysiological changes in tubular cells, potentially affecting tubular injury or tubular regeneration. We investigated the effect of a low dose of myoglobin on vascular cell adhesion molecule-1 (VCAM-1) expression and elucidated the underlying signaling pathways. We further examined the effect of losartan and simvastatin on myoglobin-induced VCAM-1 expression and the signaling pathways. METHODS: Activation of nuclear factor (NF)-kappaB and activator protein (AP)-1 was assessed by electrophoretic mobility shift assay. Phosphorylation of protein kinases was examined by Western blot analysis. VCAM-1 mRNA and protein were measured by Northern blot analysis and cell ELISA. RESULTS: A sublethal dose of myoglobin (100 microg/ml) induced VCAM-1 expression via activation of AP-1 and NF-kappaB, which was mediated through activation of c-Src kinase, followed by mitogen-activated protein kinases (p38, ERK 1/2, JNK-1) and the I kappaB kinase - I kappaB-alpha. Inhibitors of protein kinase C and tyrosine kinase, antioxidants and intracellular calcium chelator suppressed myoglobin-induced activation of c-Src kinase. Losartan and simvastatin suppressed myoglobin-induced VCAM-1 expression via inhibition of c-Src kinase. CONCLUSION: VCAM-1 expression via c-Src kinase-AP-1/NF-kappaB pathways might be one of the possible mechanisms linking myoglobin to tubular injury. Losartan and simvastatin might be beneficial in attenuating myoglobin-induced tubular injury.

Fatty acid-bearing albumin induces VCAM-1 expression through c-Src kinase-AP-1/NF-kB pathways: effect of L-carnitine.

BACKGROUND: Fatty acid-bearing albumin [FA(+) albumin] exerts more deleterious effects in tubular cells than albumin alone. We investigated the effect of FA(+) albumin on the vascular cell adhesion molecule-1 (VCAM-1) expression and elucidated the underlying signaling pathways. We further examined the effect of L-carnitine, since it was known to modulate intracellular fatty acid concentration. METHODS: Activation of AP-1 and NF-kappaB was assessed by electrophoretic mobility shift assay. Phosphorylation of protein kinase was examined by Western blot analysis. VCAM-1 mRNA and protein expression were measured by Northern blot analysis and cell ELISA. RESULTS: FA(+) albumin induced VCAM-1 expression via activation of AP-1 and NF-kappaB, which was mediated through activation of c-Src kinase, followed by MAP kinases (p38, ERK 1/2, JNK-1) and IkappaB kinase and IkappaB-alpha, respectively. Inhibitors of protein kinase C and tyrosine kinase, anti-oxidants and intracellular calcium chelator suppressed the FA(+) albumin-induced activation of c-Src kinase. L-Carnitine suppressed the FA(+) albumin-induced VCAM-1 expression via inhibition of c-Src kinase. CONCLUSIONS: VCAM-1 expression with activation of c-Src kinase-AP-1/NFkappaB pathways might be one of the possible mechanisms that linked FA(+) albumin to tubulointerstitial injury. L-Carnitine might be beneficial in attenuating FA(+) albumin-induced tubular injury.

Desmopressin improves platelet dysfunction measured by in vitro closure time in uremic patients.

BACKGROUND/AIMS: Desmopressin decreases bleeding time in uremic patients. Although bleeding time is the most frequently used measure of global platelet function, this test has important disadvantages. In vitro closure time (CT) is a relatively new and efficient test of primary hemostasis. We designed a prospective randomized study to evaluate the effect of desmopressin on platelet function, as measured by in vitro CT, in uremic patients. METHODS: Forty-eight uremic patients, about to commence hemodialysis and with prolonged CT, were randomized to infusion with desmopressin (n = 24) or saline alone (n = 24). Complete blood count, prothrombin time, activated partial thrombin time, levels of plasma fibrinogen, von Willebrand factor (VWF), factor VIII (FVIII) and CT were measured before and 1 h after desmopressin or saline infusion. RESULTS: Following desmopressin infusion, collagen/epinephrine and collagen/adenosine diphosphate CT were significantly shortened from 212 +/- 58 to 152 +/- 45 s (p = 0.01) and from 189 +/- 78 to 147 +/- 58 s (p = 0.012), respectively; levels of FVIII and VWF were significantly increased from 188 +/- 66 to 252 +/- 93% (p = 0.017) and from 113 +/- 9 to 121 +/- 9% (p = 0.043), respectively. There were no significant changes in the control group. CONCLUSIONS: Desmopressin improved platelet dysfunction and increased the plasma concentrations of VWF and FVIII, suggesting that desmopressin may play a role in improving the bleeding tendency in uremic patients.