Correction: Short-term anti-proteinuric effect of tacrolimus is not related to preservation of the glomerular filtration rate in IgA nephropathy: A 5-year follow-up study.

[This corrects the article DOI: 10.1371/journal.pone.0188375.].

Short-term anti-proteinuric effect of tacrolimus is not related to preservation of the glomerular filtration rate in IgA nephropathy: A 5-year follow-up study.

BACKGROUND: The immunosuppressive drug tacrolimus has the short-term effect of reducing proteinuria in patients with immunoglobulin A nephropathy (IgAN). Our study investigated the effects on proteinuria and kidney function after discontinuation of tacrolimus. METHODS: Patients with biopsy-proven IgAN were included in the study and randomly divided into two treatment groups. There was a corresponding control group for each treatment group. The first group included patients treated with tacrolimus (Tac vs non-Tac group) and the second group included patients with a renin angiotensin system blocker (RASi vs non-RASi group). The Tac group received treatment for up to 16 weeks, with the administration of tacrolimus being ceased at the final visit (trial phase). We tracked the patients at 12, 24, 52, and 240 weeks (observational phase). The primary outcomes examined were the percentage change (from the trial phase to the observational phase) of time-averaged proteinuria (TA-proteinuria; g/g creatinine [cr]) and the estimated glomerular filtration rate (eGFR). Time-averaged proteinuria was defined as the average of urine protein to creatinine ratio (UPCR), measured every 3 months during both the trial and observational phases of the study. RESULTS: A significant reduction in UPCR was observed in the Tac group compared to non-Tac group at the 4 and 8 week visits during the trial phase (p = 0.023 and p = 0.003, respectively). However, the difference between the Tac group and non-Tac group was not evident in the other review periods, estimated by linear mixed effect model. The percentage change in TA-proteinuria was greater in the Tac group than that in the corresponding control group (116 ± 96% vs. 63 ± 239%, p = 0.004). Therefore, during the observational phase, TA-proteinuria was not significantly different between the Tac group and the non-Tac group (1.150 ± 0.733 g/g cr vs. 1.455 ± 2.017 g/g cr, p = 0.775). The levels of eGFR throughout the observational phase were not significantly different between the two groups. Furthermore, the mean rate of eGFR change throughout both phases of the study was -6.4 ± 5.9 mL/min/1.73 m2/year in the non-Tac group and -5.4 ± 7.9 mL/min/1.73 m2/year in the Tac group (p = 0.988). CONCLUSION: The anti-proteinuric effect of tacrolimus was promptly reversed 3 months after discontinuing the drug. The use of tacrolimus for a short period of time for patients with IgAN temporarily reduces proteinuria, but the data showed no long-term efficacy regarding proteinuria reduction and improvement of renal function.

Tacrolimus decreases albuminuria in patients with IgA nephropathy and normal blood pressure: a double-blind randomized controlled trial of efficacy of tacrolimus on IgA nephropathy.

BACKGROUND: Treatment remains uncertain for IgA nephropathy patients with mild to moderate proteinuria, for whom anti-hypertensive medication or the RAS blocker is not applicable due to low blood pressure. TRIAL DESIGN: A double blinded randomized trial. METHODS: The anti-proteinuric effect of tacrolimus was explored for 40 biopsy-proven mild IgA nephropathies for 16 weeks. We randomly assigned patients either to receive tacrolimus or placebo with stratification by using a renin angiotensin system blocker. The primary outcome was the percentage change of final UACR compared to the baseline value (pcUACR). RESULTS: The mean value of pcUACR at 12-week and 16-week visits (primary outcome) was decreased more in the Tac group compared to the control group (-52.0±26.4 vs -17.3±29.3%, p = 0.001). At each visit, pcUACR was also decreased more in the Tac group compared to the control group. In the Tac group, the pcUACRs were -60.2±28.2%, -62.2±33.9%, -48.5±29.8%, and -55.5±24.0%, and, in the control group, -6.8±32.2%, -2.5±35.9%, -12.7±34.2%, and -21.9±30.6%, at 4-week, 8-week, 12-week, and 16-week visits, respectively. The pre-defined secondary outcomes were better in the Tac group compared to the control group. The frequency of decrease in pcUACR and percentage change of UPCR (pcUPCR) ≥50% at 16 weeks were 65.0% (13/20) and 55.0% (11/20)in the Tac group, and 25.0% (5/20) and 15.0% (3/20), in the control group, respectively (p = 0.025 for pcUACR and p = 0.019 for pcUPCR). However, tacrolimus wasn't effective with a dose of 0.05 mg/kg/day in patients taking ARB. The adverse events were tolerable. CONCLUSION: Tacrolimus effectively reduced proteinuria in IgA nephropathy with normal blood pressure. This suggested that tacrolimus could be an alternative to corticosteroid and RAS blocker for IgA nephropathy patients who cannot endure anti-hypertensive medication. TRIAL REGISTRATION: Clinicaltrial.gov NCT1224028.

The low number of red blood cells is an important risk factor for all-cause mortality in the general population.

Patients with advanced chronic kidney disease (CKD) show decreased hemoglobin levels. We aimed to verify the changes of red blood cell (RBC) number according to glomerular filtration rate (GFR) levels and its influence on the clinical outcome. With the data from routine health checkups of 114,496 adults, we grouped the subjects according to quartile levels of RBC number in each gender. Mortality data were from the National Statistical Office. RBC number was increased with decreasing GFR and/or the presence of a component of metabolic syndrome (MS) in subjects with GFR ≥ 50 ml/min/1.73 m². The estimated mean RBC number of subjects with GFR 89-50 ml/min/1.73 m² was higher compared to those with GFR ≥ 100 ml/min/1.73 m² by ANCOVA. In men, the death rate was the highest in the 1st quartile group (1Q) of RBC number (1.22%), followed by the 2nd quartile group (2Q, 0.42%), the 3rd quartile group (3Q, 0.39%), and the 4th quartile group (4Q, 0.29%) (p < 0.001). The hazard ratio (HR) of death in 2Q, 3Q and 4Q was 0.446, 0.580, and 0.440, respectively, compared to 1Q (p < 0.001). Among men in 1Q group, subjects with hemoglobin < 14.0 g/dL showed higher mortality rate than those with hemoglobin 14.0-14.9 g/dL or ≥ 15.0 g/dL (2.3% : 0.8% : 1.1%, respectively, p < 0.001). In conclusion, the RBC number was increased according to declines of GFR in the range of GFR ≥ 50 ml/min/1.73 m² and was an important risk factor for mortality.

Complete remission induced by tacrolimus and low-dose prednisolone in adult minimal change nephrotic syndrome: A pilot study.

BACKGROUND: Few clinical trials have examined the replacement of steroids with other immunosuppressive drugs as a primary treatment modality for minimal change disease (MCD) in adults. We studied the efficacy of tacrolimus to induce complete remission (CR) in adults with MCD. METHODS: We enrolled 14 adults with MCD and nephrotic-range proteinuria. All patients were treated with oral tacrolimus 0.05 mg/kg twice daily and prednisolone 0.5 mg/kg/day. CR was defined as a urine protein to creatinine ratio of<0.2 g protein/g creatinine (g/g cr). The primary outcome was cumulative percentage of CR during 16 weeks. RESULTS: The mean urine protein to creatinine ratio at enrollment was 10.9 g/g cr (range: 4.2-18.1 g/g cr). The trough tacrolimus level was maintained at 5.99±2.63 ng/mL. CR was achieved by 13/14 (92.8%) patients within 8 weeks. The cumulative CR rate was 7.7% (1/14), 64.2% (9/14), 71.3% (10/14), and 92.9% (13/14) at 1 week, 2 weeks, 4 weeks, and 8 weeks, respectively. The one remaining patient achieved CR at 20 weeks after treatment, who was followed up for a further 4 weeks. The mean time to achieve CR in the 14 patients was 4.64±5.11 (1-20) weeks. Three cases suffered adverse events of abdominal pain, diarrhea, or new-onset diabetes mellitus. CONCLUSION: Tacrolimus and low-dose prednisolone therapy induced CR rapidly (71.3% by 4 weeks and 100% by 20 weeks) and effectively in adult patients with MCD.

[Biliary-duodenal fistula following radiofrequency ablation therapy for hepatocellular carcinoma].

Hepatocellular carcinoma (HCC) is one of the most common malignant neoplasms occurring worldwide. Surgical resection currently provides the best chance of long-term tumor free survival, but the most HCCs are not candidates for surgical excision due to poor liver function or poor medical background. Numerous noninvasive alternatives to surgical resection have been introduced to treat liver cancers. Radiofrequency thermal ablation has begun to receive much attention as an effective and minimally invasive technique for the local control of HCC. The biliary system related complications after radiofrequency ablation has rarely been reported. We report a case of biliary-duodenal fistula with liver abscess after radiofrequency ablation for HCC. The case was treated by abscess drainage and antibiotics.