Seungyeup Han

Nephrotic syndrome causes upregulation of HDL endocytic receptor and PDZK-1-dependent downregulation of HDL docking receptor

BACKGROUNDnNephrotic syndrome (NS) is associated with dysregulation of lipid/lipoprotein metabolism and impaired high-density lipoprotein (HDL)-mediated reverse cholesterol transport and atherosclerosis. HDL serves as vehicle for transport of surplus lipids from the peripheral tissues for disposal in the liver via two receptors: (i) scavenger receptor class B type I (SR-BI) which serves as a docking receptor, enabling HDL to unload its lipid cargo and return to circulation to repeat the cycle, and (ii) beta chain ATP synthase which serves as the endocytic receptor mediating removal and catabolism of lipid-poor HDL. SR-BI abundance is regulated by PDZ-containing kidney protein 1 (PDZK1), a multifunctional protein, which prevents SRB-1 degradation at the post-translational level. This study explored the effect of NS on hepatic expression of these important molecules.nnnMETHODSnGene expression, protein abundance and immunohistological appearance of the above proteins were measured in the liver of rats with puromycin-induced NS and control rats.nnnRESULTSnThe nephrotic animals exhibited severe proteinuria, hypoalbuminemia, hypercholesterolemia, hypertriglyceridemia, reduced HDL/total cholesterol ratio, normal glomerular filtration rate, significant upregulation of the endocytic HDL receptor messenger RNA (mRNA) and protein (P < 0.005) and significant reduction of SR-BI protein (P < 0.002) despite its normal mRNA abundance. The reduction in SR-BI protein abundance in NS animals was accompanied by parallel reductions in PDZK1 mRNA (P = 0.02) and protein abundance (P = 0.012).nnnCONCLUSIONSnNS results in elevation of hepatic HDL endocytic receptor and deficiency of HDL docking receptor. The latter is associated with and, in part, mediated by downregulation of PDZK1. Together, these abnormalities can increase catabolism and diminish recycling of HDL and contribute to the defective reverse cholesterol/lipid transport in NS.

Use of early postoperative MAG3 renal scan to predict long-term outcomes of renal transplants.

OBJECTIVESnA Tc-99m mercaptoacetyltriglycine renal scan has been used to evaluate perfusion and excretory function of renal allografts. A Tc-99m mercaptoacetyltriglycine renal scan has been reported to correlate with early allograft outcomes. This study was done to determine whether a Tc-99m mercaptoacetyltriglycine renal scan has any relation with long-term renal transplant outcomes.nnnMATERIALS AND METHODSnA total of 311 consecutive kidney transplant recipients were included in the study. All had Tc-99m mercaptoacetyltriglycine renal scans on posttransplant days 3 and 7. Patterns of the renography curve was graded as follows: 0=normal perfusion and excretion; 1=normal perfusion, reduced excretion; 2=normal perfusion, flat excretion; and 3=reduced perfusion and rising curve. Early postoperative Tc-99m mercaptoacetyltriglycine scintigraphy findings were correlated with serum creatinine values, acute rejection episodes, and long-term graft survival.nnnRESULTSnA Tc-99m mercaptoacetyltriglycine renography of a deceased-donor kidney transplant showed a significantly higher grade on both days 3 and 7 than did live-donor kidney transplant (P < .001). Serum creatinine was positively correlated with the renography grades on days 3 and 7. The acute rejection rate was higher in the renography on days 3 and 7. Grade 2 renography on day 3 showed a significantly higher graft failure rate compared with the other grades (8.8% vs 8.6% vs 31.6% vs 7.3%; P = .014). Also, the renography showed the worst 5-year graft survival rate (95.9% vs 93.3% vs 89.5% vs 94.1%; P = .019). There were no differences in the graft failure rate or in graft survival rate according to the Tc-99m mercaptoacetyltriglycine renography grades on day 7.nnnCONCLUSIONSnOur data show that a Tc-99m mercaptoacetyltriglycine renography grade correlate not only with early postoperative kidney function and incidence of acute rejection, but also with long-term outcomes of a renal allograft. A grade 2 renography pattern, with normal uptake and flat excretion, indicates a dismal prognosis for the long-term allograft survival.

Long Term Outcomes of Kidney Transplantation With Primary Glomerulonephritis

Introduction The clinical outcomes after kidney transplantation (KT) vary according to the types of glomerulonephritis (GN) causing end-stage renal disease (ESRD). In addition, the recurrence of GN has a significant impact on the outcomes of KT. In the present study, we evaluated clinical outcomes of KT in patients with biopsy-proven GN. Methods All KT recipients who had biopsy proven GN and had been transplanted between Nov. 1982 and Jan. 2017 were enrolled. We investigated the incidence of recurrent GN and analyzed the factors associated with recurrence, allograft survival, and patient survival. Results Of 1253 patients who received KT, 183 had a biopsy-proven GN as the cause of ESRD. The types of GN were immunoglobulin A nephropathy (IgAN) in 95 patients, focal segmental glomerulosclerosis (FSGS) in 47, membranous proliferative glomerulonephritis (MPGN) in 14, membranous glomerulonephritis (MGN) in 9, lupus nephritis in 8, rapid progressive glomerulonephritis (RPGN) in 6, and alport syndrome in 4. The mean follow up duration was 103 ± 81.7 months. Recurrent GN occurred in 36 patients (19.7%) and recurrence rate was 25.5% in FSGS, 22.2% in MGN, 21.4% in MPGN and 20.0% in IgAN. The recurrence of GN was more common in younger patients at the time of KT (p=0.03). Twenty of the 36 patients with recurrent GN lost their allograft due to recurrence. Discussion The rate of graft failure in recipients with recurrence was higher than those without recurrence (55.6%, 18.4%, p=0.000). The recurrence of GN rather than the type of GN was a significant risk factor for allograft loss. (adjusted hazard ratio 1.89 [1.004-3.368]). Conclusion The recurrence of GN was significant risk factor for allograft loss. In particular, younger recipients were more likely to go through recurrence after KT. Further studies are required to evaluate optimal strategies to prevent and treat recurrent GN after KT.

Multiple tuberculomas invading the central nervous system as a paradoxical reaction in a kidney transplantation recipient

A paradoxical reaction during anti-tuberculosis (anti-TB) therapy is commonly reported in patients with human immunodeficiency virus (HIV). However, a similar reaction to anti-TB therapy can also occur in patients without HIV, especially in patients who have undergone solid organ transplantation. A 65-year-old woman who underwent kidney transplantation six months prior presented to our emergency room with progressive paraparesis. She had been diagnosed with drug-susceptible miliary TB and had undergone two weeks of treatment with anti-TB medication. Magnetic resonance imaging showed a spinal intramedullary mass and multiple intracranial nodules. The etiology of the lesions was confirmed as Mycobacterium tuberculosis. We report a paradoxical reaction of spinal intramedullary and multiple intracranial tuberculomas in a patient with miliary TB who had received appropriate treatment for more than two weeks.

Clinical significance of the Kidney Donor Profile Index in deceased donors for prediction of post-transplant clinical outcomes: A multicenter cohort study

Background We investigated whether the Kidney Donor Profile Index (KDPI) system is useful in predicting clinical outcomes in deceased donor kidney transplantation (DDKT). Methods Four hundred sixty-nine kidney transplant recipients (KTRs) receiving kidneys from 359 deceased donors were included in this study, which involved three transplant centers. KTRs were divided into high and low KDPI KTR groups based on the median KDPI score of 67%. We compared clinical outcomes between the high KDPI and low KDPI groups. Results There were no significant differences in the incidence of delayed graft function and acute rejection between high and low KDPI KTR groups. In comparison with histologic findings in allograft tissues obtained within three months from KT, the proportion of glomerulosclerosis was significantly higher in the high KDPI KTR group than in the low KDPI KTR group. With Kaplan-Meier analysis, the graft survival rate was significantly lower in the high KDPI KTR group than in the low KDPI KTR group (Log rank, P = 0.017), and multivariate analysis also demonstrated that a high KDPI score was a significant risk factor for death censored allograft failure (HR 2.62, 95% CI, 1.29–5.33, P = 0.008). Conclusion The KDPI scoring system is useful in predicting allograft outcomes in a Korean DDKT cohort.

Comparison of Clinical Outcomes of Deceased Donor Kidney Transplantation according to Donor Evaluation Criteria

Introduction Deceased donor kidney transplantation (DDKT) in Korea has been activated recently. However, discrepancies between needs and supply are still increasing, and the use of donors with acute kidney injury (AKI), expanded criteria (ECD), or high kidney donor profile index (KDPI) is also increasing. We investigated the clinical outcomes of DDKT in relation to AKI, ECD, and KDPI. Methods We retrospectively analyzed DDKT performed at Keimyung University hospital between 2010 and 2014. Ninetyfour DD and their corresponding 95 KT recipients were included in this study. Results The mean follow-up period was 42.6 ± 17.4 months (range 2‐81). Patients belonging to the AKI group were 42 (44.2%), ECD group were 23 (24.2%), and high KDPI (>85%) group were 16 (16.8%). The incidence of delayed graft function (DGF) was significantly higher in the AKI group than in the non-AKI group (P = 0.011), but not in the ECD group and the high KDPI group. The estimated glomerular filtration rate (eGFR) of the AKI group was significantly lower at 1 week, 2 weeks and 1 month after KT compared to the non-AKI group. After 3 months of KT, there was no significant difference in eGFR between the AKI group and non-AKI group, the ECD group and standard criteria donor group, and the high KDPI group and low KDPI group. Allograft survival rate showed no significant difference in the AKI, ECD, and high KDPI groups compared with the control groups. However, allograft survival rate was significantly lower only in the group with acute rejection (AR) than in the group without AR (P < 0.001). Patient survival rate showed no significant difference, according to donor AKI, ECD, or high KDPI. In multivariate analysis, AR was an independent risk factor for graft failure (hazard ratio 85.75, 95% confidence interval, 7.02-1047.77, P < 0.001), but AKI, ECD, or high KDPI were not. Conclusion Donors with AKI showed significant association with incidence of DGF. However, kidneys with AKI, ECD, or high KDPI performed similarly to the control group in terms of graft function, graft survival, and patient survival. More detailed criteria for selecting a proper donor will be needed.

MP661ELEVATED PLASMA CYCLOPHILIN A IN HEMODIALYSIS AND PERITONEAL DIALYSIS PATIENTS: A NOVEL LINK TO SYSTEMIC INFLAMMATION AND CARDIOVASCULAR DISEASE

Author(s): Jin, Kyubok; Vaziri, Nosratola D; Kim, Yaerim; Kang, Seong Sik; Park, Woo Yeong; Han, Seungyeup; Park, Sung Bae; Park, Sihyung; Yoon, Jeongsoo

A case of CMV infection and encapsulating peritoneal sclerosis in a renal transplant recipient

Encapsulating peritoneal sclerosis (EPS) is a rare but severe complication of peritoneal dialysis. It has been reported that the condition of patients with EPS may improve after renal transplantation. However, there are also several reports of EPS occurring after renal transplantation. In this report, we present a patient who developed EPS combined with gastrointestinal cytomegalovirus infection 21 months after successful renal transplantation, despite the use of tacrolimus and low-dose steroid as maintenance immunosuppression.