Effect of Pravastatin on Kidney Function in Patients with Dyslipidemia and Type 2 Diabetes Mellitus: A Multicenter Prospective Observational Study.

INTRODUCTION: Several studies have reported that pravastatin can mitigate the progression of kidney disease, but limited evidence exists regarding its effects on kidney function in Asian patients. This multicenter prospective observational study aimed to assess the effect of pravastatin on kidney function in Korean patients with dyslipidemia and type 2 diabetes mellitus (T2DM) in clinical practice. METHODS: This 48-week prospective multicenter study included 2604 of 2997 eligible patients with dyslipidemia and T2DM who had available estimated glomerular filtration rate (eGFR) measurements. The primary endpoint was eGFR percent change at week 24 from baseline. We also assessed secondary endpoints, which included percent changes in eGFR at weeks 12 and 48 from baseline, as well as changes in eGFR, metabolic profiles (lipid and glycemic levels) at 12, 24, and 48 weeks from baseline, and safety. RESULTS: We noted a significant improvement in eGFR, with mean percent changes of 2.5%, 2.5%, and 3.0% at 12, 24, and 48 weeks, respectively (all adjusted p < 0.05). The eGFR percent changes significantly increased in subgroups with baseline eGFR 30-90 mL/min/1.73 m2, glycated hemoglobin (HbA1c) ≥ 7 at baseline, no hypertension history, T2DM duration > 5 years, or previous statin therapy. Lipid profiles were improved and remained stable throughout the study, and interestingly, fasting glucose and HbA1c were improved at 24 weeks. CONCLUSION: Our findings suggest that pravastatin may have potential benefits for improving eGFR in Korean patients with dyslipidemia and T2DM. This could make it a preferable treatment option for patients with reduced kidney function. TRIAL REGISTRATION NUMBER: NCT05107063 submitted October 27, 2021.

Nrf2-Heme oxygenase-1 modulates autophagy and inhibits apoptosis triggered by elevated glucose levels in renal tubule cells.

BACKGROUND: Autophagy is a highly balanced process in which lysosomes remove aged and damaged organelles and cellular proteins. Autophagy is essential to maintain homeostasis in the kidneys. METHODS: Using human renal tubule cells HK-2, we assessed the impact of high glucose (HG) on autophagy. We also evaluated the capability of sulforaphane (SFN) to protect the HK-2 cells from HG-induced apoptosis by modulating autophagy. RESULTS: SFN modulated autophagy and decreased apoptosis in the HK-2 cells that were cultured in 250 mM glucose medium for two days. The reactive oxygen species (ROS) levels increased, as expected, in the cells cultured in the 250 mM glucose medium. However, the SFN decreased the ROS levels in the HK-2 cells. The overexpression of heme oxygenase-1 (HO-1) by SFN decreased the expression of LC3 and beclin-1. LC3 and beclin-1 were involved in the downregulation of caspase-3 that was observed in the HG-induced cells. CONCLUSION: The activation of nuclear factor E2-related factor 2 (Nrf2)-HO-1 inhibited ROS expression and subsequently attenuated autophagy and cell apoptosis after HG injury was decreased. HG injury led to the activation of autophagy and HO-1 in order to combat oxidative stress and protect against cell apoptosis. Therefore, HO-1 activation can prevent ROS development and oxidative stress during HG injury, which considerably decreases autophagy and apoptosis.

Fibrillary glomerulonephritis combined with chronic inflammatory demyelinating polyneuropathy.

A 58-yr-old man presented with leg edema and subacute weakness of his bilateral lower extremities. Urinary and serum immunoelectrophoresis revealed the presence of lambda-type Bence Jones proteins. He was ultimately diagnosed with monoclonal gammopathy of undetermined significance (MGUS). A renal biopsy specimen showed fibrillary glomerulonephritis (FGN), which was randomly arranged as 12-20 m nonbranching fibrils in the basement membranes. Immunofluorescence studies were negative for immunoglobulin (Ig)G, IgM, IgA, C3, and kappa light chains in the capillary walls and mesangial areas. A Congo red stain for amyloid was negative. Electromyography and nerve conduction velocity examinations results were compatible with the presence of demyelinating polyneuropathy. This case showed a rare combination of FGN, without Ig deposition, and MGUS combined with chronic inflammatory demyelinating polyneuropathy (CIDP).

Effect of topical vitamin D on chronic kidney disease-associated pruritus: An open-label pilot study.

Chronic kidney disease-associated pruritus (CKD-aP) is a troublesome symptom in patients with end-stage renal disease (ESRD). Recently, vitamin D deficiency has been known to be one of the possible etiologic factors in CKD-aP. However, limited data is available on whether topical vitamin D treatment is effective for relieving CKD-aP. Therefore, the purpose of this study is to evaluate the effectiveness of topically vitamin D for CKD-aP. Twenty-three patients with CKD-aP were enrolled in a single center, open-label study. Patients were instructed to apply a topical vitamin D (calcipotriol) agent (Daivonex solution; LEO Pharma) or vehicle solution twice daily for a month. We assessed the efficacy and safety of topical vitamin D on CKD-aP using clinical and dermoscopic photographs, and questionnaires including the validated modified pruritus assessment score (VMPAS) and visual analog scale (VAS) every 2 weeks. Dry dermoscopic findings showed significant improvement of scale (dryness) on the skin of topical vitamin D-treated patients compared with those of the vehicle group. Both VMPAS and VAS were significantly decreased after 2 and 4 weeks of the topical vitamin D treatment compared with the vehicle, respectively (P < 0.05). No significant side-effects were observed. Topical vitamin D may be one of the safe and effective therapeutic candidates for CKD-aP.

Weak response of porcine C5a receptor towards human C5a in miniature pig endothelial cells and PMNs.

BACKGROUND: The anaphylatoxin C5a is a potent inflammatory molecule generated during complement activation. Although some reports have implicated C5a in xenograft rejection, to date, the molecular compatibility between human C5a and porcine C5a receptor (C5aR) has been little studied. To examine the need for pC5aR-deficient pig in xenotransplantaion, we aimed to look at the degree of direct interaction between human C5a (recipient side) and porcine endothelial cells (PECs) and porcine polymorphonuclear neutrophils (PMNs) (donor side). METHODS: Following the treatment of human C5a to isolated porcine PMNs, transmigration of PMNs was measured by Transwell system and superoxide generation by cytochrome c reduction assay. Next, the effects of human C5a on several intracellular signaling pathways were further checked; actin cytoskeletal change was observed under a confocal microscope after staining with Alexa Fluor-546-phalloidin, intracellular calcium mobilization was measured by spectrofluorophotometer. The degree of direct effect of human C5a on porcine PMNs was compared with that in human PMNs. Finally, microarray was performed to monitor the effect of human C5a on gene expression of PEC and the expression of several candidate proteins was checked by flow cytometry. RESULTS: We found that human C5a was able to induce chemotaxis, superoxide generation, actin cytoskeletal change, and intracellular calcium mobilization in porcine PMNs. However, higher concentration of human C5a was required to stimulate porcine PMNs in comparison with activating human PMNs. The amino acid sequences of porcine C5aR with those of human C5aR showed a sequence homology of only 67%. To elucidate the effect of human C5a to PECs, microarray analysis following the treatment of PECs with human C5a was performed. These data showed that human C5a did not significantly affect gene transcription patterns in PECs. Additionally, treatment of PECs with human C5a also did not induce protein expression of several cell adhesion molecules, including vascular cell adhesion molecule-1, intercellular adhesion molecule-1, P-selectin, and E-selectin, or secretion of interleukin-8 from PECs. CONCLUSIONS: These results suggest that human C5a may play a minor role on PEC activation possibly due to molecular incompatibility across the species barrier.

[Optimal cut-off value of PIVKA-II for diagnosis of hepatocellular carcinoma--using ROC curve].

BACKGROUND/AIMS: Protein induced by vitamin K absence or antagonist-II (PIVKA-II), also known as des-carboxyprothrombin (DCP), can be used as an alternative tool to alpha-fetoprotein (AFP) for surveillance of hepatocellular carcinoma (HCC). The aims of the present study were to compare PIVKA-II levels between the patients with HCC and patients with non-HCC chronic liver disease, to evaluate the correlation of PIVKA-II and AFP in HCC patients, and finally to estimate the optimal cut-off value for PIVKA-II for the diagnosis of HCC with using the receiver operating characteristic (ROC) curve. METHODS: A total of 227 consecutive patients with HCC (n=42) or chronic liver disease (n=185) were enrolled in this study. HCC was diagnosed histologically or by imaging such as computed tomography, magnetic resonance imaging or angiography. The serum PIVKA-II and AFP levels were measured by electrochemiluminoimmunoassay with using the Haicatch PIVKA-II kit and by immunoradiometric assay, respectively. RESULTS: The PIVKA-II level in the HCC patients was significantly higher than the non-HCC chronic liver disease patients (903.0+/-1156.7 vs. 111.7+/-211.0 mAU/ mL, respectively, P<0.01). PIVKA-II and AFP showed a statistical correlation in HCC patients (r=0.46, P<0.01). The sensitivity and specificity of PIVKA-II for the diagnosis of HCC were 66.7% and 74.1%, respectively, and when tasted together with AFP, the sensitivity was increased by 85.7%. For the ROC curve of PIVKA-II in HCC patients, the specificity of a 250 mAU/mL level of PIVKA-II was 95%. CONCLUSIONS: PIVKA-II was as useful surveillance tool for differentiating HCC from chronic liver disease, and a PIVKA-II value of 250 mAU/ mL was proposed as a significant cut-off value for diagnosis of hepatocellular carcinoma.

Concurrence of Sjögren's syndrome in a patient with Chlamydia-induced reactive arthritis; an unusual finding.

A 40-year-old Korean man presented with painful swelling and tenderness of both ankle joints as well as the plantar surfaces of both feet, along with inflammatory back pain, and a purulent discharge from the urethral orifice. The patient also complained of sicca-like symptoms including dry eyes and dry mouth. An immunological analysis revealed a high titer of rheumatoid factor, positive results for antinuclear antibody and anti-Ro antibody, and a positive result for HLA-B27. An antibody titer for Chlamydia was also significantly increased. Positive results of the Schirmer's test and for keratoconjunctivitis sicca were confirmed by an ophthalmologist. These clinical manifestations were compatible with Chlamydia-induced reactive arthritis (ReA) accompanied by Sjögren's syndrome (SS). This is the first report of the combination of these two distinct disease entities in the Korean population.