Jung Pyo Lee

Incidence and Outcomes of Contrast-Induced Nephropathy After Computed Tomography in Patients With CKD: A Quality Improvement Report

BACKGROUND Although there has been considerable investigation of the general characteristics of contrast-induced nephropathy (CIN), it has not been studied adequately in a computed tomography (CT) population. We assessed the incidence and outcomes of CIN after contrast-enhanced CT in patients with chronic kidney disease pretreated with saline and N-acetylcysteine (NAC). DESIGN Quality improvement report. SETTING & PARTICIPANTS 520 patients registered in a CIN prevention program. QUALITY IMPROVEMENT PLAN We initiated the CIN prevention program in January 2007. In this program, patients with chronic kidney disease undergoing contrast-enhanced CT in an outpatient setting were automatically referred to nephrologists, and patients received saline and NAC before and after CT. The development of CIN was assessed 48-96 hours after CT. OUTCOMES Incidence of CIN and time to renal replacement therapy. MEASUREMENTS Baseline serum creatinine, hemoglobin, and serum albumin levels; type and volume of contrast agents; and post-CT serum creatinine level. RESULTS Overall, CIN occurred in 13 (2.5%) patients. Incidences of CIN were 0.0%, 2.9%, and 12.1% in patients with an estimated glomerular filtration rate of 45-59, 30-44, and <30 mL/min/1.73 m(2), respectively. The risk of CIN was increased in patients with severely decreased kidney function and diabetes. The development of CIN consequently increased the risk of renal replacement therapy (P < 0.001 by log-rank), and the risk was significantly accentuated in patients with estimated glomerular filtration rate <30 mL/min/1.73 m(2). LIMITATIONS A single-center study and comparison with previous studies. CONCLUSIONS The incidence of CIN was relatively low in patients treated with saline and NAC. The development of CIN predisposed to poor kidney survival in the long term.

Risk factors for consequent kidney impairment and differential impact of liver transplantation on renal function

BACKGROUND Chronic kidney disease (CKD) develops frequently after liver transplantation (LTx), and it is important to identify and correct risk factors that negatively affect kidney function. Risk factors have not been well evaluated in Asian countries where hepatitis B virus (HBV) infection is a dominant cause. METHODS Four hundred thirty-one Korean recipients who underwent LTx between 1997 and 2008 were analysed. CKD was defined as a sustained decrease in estimated glomerular filtration rate (eGFR) of <60 (mL/min/1.73 m(2)) for at least three consecutive months using an abbreviated Modification in Renal Disease (MDRD) formula. RESULTS Eighty percent of the patients had HBV-related underlying diseases. The recipients whose pretransplant eGFR had been low (<30 mL/min/1.73 m(2)) improved their renal function after LTx, but significant functional decline occurred in recipients whose pretransplant eGFR was high (>or=60 mL/min/1.73 m(2)). A multivariate Cox regression analysis revealed that the overall risk of CKD development (eGFR < 60 mL/min/1.73 m(2)) was associated with old age of recipients, cyclosporine, posttransplant acute renal failure (ARF), cause [calcineurin inhibitor (CNI) nephrotoxicity] and severity of posttransplant ARF, low pretransplant eGFR, pretransplant hepatorenal syndrome, pretransplant proteinuria, high Child-Pugh score and high Model for End-Stage Renal Disease (MELD) score. Especially in recipients whose pre-operative eGFR was high (>or=60 mL/min/1.73 m(2)), rapid progression of kidney disease was associated with high tacrolimus level, non-HBV disease, posttransplant ARF, cause (CNI nephrotoxicity) and severity of posttransplant ARF and Child-Pugh score. CNI toxicity and focal segmental sclerosis, but not immune-complex disease, were revealed as significant contributors to CKD after LTx in HBV recipients. CONCLUSION Judicious use of CNIs should be applied to liver recipients to prevent kidney dysfunction.

Sulfatide-Reactive Natural Killer T Cells Abrogate Ischemia-Reperfusion Injury

There is a significant immune response to ischemia-reperfusion injury (IRI), but the role of immunomodulatory natural killer T (NKT) cell subtypes is not well understood. Here, we compared the severity of IRI in mice deficient in type I/II NKT cells (CD1d(-/-)) or type I NKT cells (Jα18(-/-)). The absence of NKT cells, especially type II NKT cells, accentuated the severity of renal injury, whereas repletion of NKT cells attenuated injury. Adoptively transferred NKT cells trafficked into the tubulointerstitium, which is the primary area of injury. Sulfatide-induced activation of type II NKT cells protected kidneys from IRI, but inhibition of NKT cell recruitment enhanced injury. In co-culture experiments, sulfatide-induced activation of NKT cells from either mice or humans attenuated apoptosis of renal tubular cells after transient hypoxia via hypoxia-inducible factor (HIF)-1α and IL-10 pathways. Renal tissue of patients with acute tubular necrosis (ATN) frequently contained NKT cells, and the number of these cells tended to negatively correlate with ATN severity. In summary, sulfatide-reactive type II NKT cells are renoprotective in IRI, suggesting that pharmacologic modulation of NKT cells may protect against ischemic injury.

Bone marrow-derived endothelial progenitor cells confer renal protection in a murine chronic renal failure model

Endothelial cell damage and impaired angiogenesis substantially contribute to the progression of chronic renal failure (CRF). The effect of endothelial progenitor cell (EPC) treatment on the progression of CRF is yet to be determined. We performed 5/6 nephrectomy to induce CRF in C57BL/6 mice. EPCs were isolated from bone marrow, grown in conditioned medium, and characterized with surface marker analysis. The serial changes in kidney function and histological features were scrutinized in CRF mice and EPC-treated CRF (EPC-CRF) mice. Adoptively transferred EPCs were present at the glomeruli and the tubulointerstitial area until week 8 after transfer. In CRF mice, renal function deteriorated steadily over time, whereas the EPC-CRF group showed less deterioration of renal function as well as reduced proteinuria along with a relatively preserved kidney structure. Renal expression of proinflammatory cytokines and adhesion molecules was already decreased in the EPC-CRF group at the early stage of disease, at which point the renal function and histology of CRF and EPC-CRF mice were not different. Angiogenic molecules including VEGF, KDR, and thrombospondin-1, which were decreased in the CRF group, were restored by EPC treatment. In conclusion, EPCs trafficked into the injured kidney protected the kidney from the inflammatory condition and consequently resulted in functional and structural renal preservation. Our study suggests EPCs as a potential candidate for a novel therapeutic approach in CRF.

Early Referral to a Nephrologist Improved Patient Survival: Prospective Cohort Study for End-Stage Renal Disease in Korea

The timing of referral to a nephrologist may influence the outcome of chronic kidney disease patients, but its impact has not been evaluated thoroughly. The results of a recent study showing an association between early referral and patient survival are still being debated. A total of 1028 patients newly diagnosed as end-stage renal disease (ESRD) from July 2008 to October 2011 were enrolled. Early referral (ER) was defined as patients meeting with a nephrologist more than a year before dialysis and dialysis education were provided, and all others were considered late referral (LR). The relationship of referral pattern with mortality in ESRD patients was explored using a Cox proportional hazards regression models. Time from referral to dialysis was significantly longer in 599 ER patients than in 429 LR patients (62.3±58.9 versus 2.9±3.4 months, P<0.001). Emergency HD using a temporary vascular catheter was required in 485 (47.2%) out of all patients and in 262 (43.7%) of ER compared with 223 (52.0%) of LR (P = 0.009). After 2 years of follow-up, the survival rate in ER was better than that in LR (hazard ratio [HR] 2.38, 95% confidence interval [CI] 1.27–4.45, P = 0.007). In patients with diabetes nephropathy, patient survival was also significantly higher in ER than in LR (HR 4.74, 95% CI 1.73–13.00, P = 0.002). With increasing age, HR also increased. Timely referral to a nephrologist in the predialytic stage is associated with reduced mortality.

Soluble epoxide hydrolase activity determines the severity of ischemia-reperfusion injury in kidney.

Soluble epoxide hydrolase (sEH) in endothelial cells determines the plasma concentrations of epoxyeicosatrienoic acids (EETs), which may act as vasoactive agents to control vascular tone. We hypothesized that the regulation of sEH activity may have a therapeutic value in preventing acute kidney injury by controlling the concentration of EETs. In this study, we therefore induced ischemia-reperfusion injury (IRI) in C57BL/6 mice and controlled sEH activity by intraperitoneal administration of the sEH inhibitor 12-(3-adamantan-1-ylureido)-dodecanoic acid (AUDA). The deterioration of kidney function induced by IRI was partially moderated and prevented by AUDA treatment. In addition, AUDA treatment significantly attenuated tubular necrosis induced by IRI. Ischemic injury induced the down-regulation of sEH, and AUDA administration had no effect on the expression pattern of sEH induced by IRI. In vivo sEH activity was assessed by measuring the substrate epoxyoctadecenoic acid (EpOME) and its metabolite dihydroxyoctadec-12-enoic acid (DHOME). Ischemic injury had no effects on the plasma concentrations of EpOME and DHOME, but inhibition of sEH by AUDA significantly increased plasma EpOME and the EpOME/DHOME ratio. The protective effect of the sEH inhibitor was achieved by suppression of proinflammatory cytokines and up-regulation of regulatory cytokines. AUDA treatment prevented the intrarenal infiltration of inflammatory cells, but promoted endothelial cell migration and neovascularization. The results of this study suggest that treatment with sEH inhibitors can reduce acute kidney injury.

Prevalence of Vitamin D Deficiency and Effects of Supplementation With Cholecalciferol in Patients With Chronic Kidney Disease

OBJECTIVE We aimed to evaluate the vitamin D status, the effect of cholecalciferol supplementation, and the factors associated with vitamin D restoration in nondialytic patients with chronic kidney disease (CKD). DESIGN The present study was a prospective open-label trial. SETTING This study took place at the Seoul National University Boramae Medical Center. SUBJECTS Patients with nondialytic CKD (estimated glomerular filtration rate [eGFR] 10-59 mL/min per 1.73 m(2)) participated in this study. INTERVENTION Vitamin D status in 210 CKD patients was assessed and the patients with vitamin D deficiency (<30 ng/mL) were administered cholecalciferol (1,000 IU/day) for 6 months. MAIN OUTCOME MEASURE The restoration rate of vitamin D deficiency at 3 and 6 months and the response-related factors were analyzed. RESULTS The prevalence of vitamin D deficiency was 40.7% in CKD Stage 3, 61.5% in Stage 4, and 85.7% in Stage 5. The subgroup with vitamin D deficiency had a greater proportion of patients with diabetes, lower eGFR, and higher proteinuria. With the supplementation, 52 patients (76.5%) reached levels of 25-hydroxy vitamin D (25(OH)D) of 30 ng/mL or greater at 3 months, and the restoration of vitamin D was observed in 61 patients (89.7%) at 6 months. Lower levels of 25(OH)D and a higher amount of proteinuria at baseline were the factors associated with lower response to vitamin D supplementation. CONCLUSION Vitamin D deficiency rate was high in nondialytic CKD patients, and the proportion increased as renal function decreased. A higher amount of proteinuria was the independent risk factor of nonresponse with supplementation. Vitamin D was replenished in most patients with cholecalciferol supplementation without any significant adverse effects.

In vivo activity of epoxide hydrolase according to sequence variation affects the progression of human IgA nephropathy

Epoxyeicosatrienoic acid (EET) regulates the functional integrity of the endothelium. It is hypothesized that the activity of epoxide hydrolase (EPHX2), which determines EET concentration through hydrolysis, may affect the progression of glomerulonephritis. Here, we evaluated the relationship between genetic variations, the in vivo activity of EPHX2, and progression of IgA nephropathy (IgAN). Three single-nucleotide polymorphisms (SNPs) [rs41507953 (K55R), rs751141 (R287Q), and rs1042032] were traced in 401 IgAN patients and 402 normal healthy controls. The in vivo activity of EPHX2 was assessed by measuring substrates/metabolites of the enzyme. None of the polymorphism frequencies differed significantly between patients and controls. However, patients carrying the variant allele (A) of rs751141 possessed better kidney survival than those with the wild-type allele (G; P < 0.001). This association remained significant after adjustment for several risk factors (hazard ratio 1.83, 95% confidence interval 1.13-2.96, P = 0.014). Vascular damage was more prominent in kidney biopsies from patients carrying the G allele of rs751141. The in vivo activity of EPHX2, assessed by the epoxyoctadecenoic acid/dihydroxyoctadecenoic acid ratio using liquid chromatography/mass spectrometry analysis, was elevated in patients with the G allele. The expression of EPHX2 in the human kidney was independent of the sequence variation of the rs751141 allele. Variant rs41507953 was not present in this cohort, and rs1042032 was not associated with progression. Thus the specific measures which regulate EPHX2 activity should be designed for potential therapeutics.

Outcome of renal allograft in patients with Henoch-Schönlein nephritis: single-center experience and systematic review.

Background. Henoch-Schönlein nephritis (HSN) is a rare condition resulting in end-stage renal disease. Therefore, graft outcomes and recurrence rates after transplantation are not well studied. Also, the effect of donor type on graft outcome has not been evaluated thoroughly. Methods. The graft outcome and recurrence rate in 20 kidney recipients with HSN were compared with age-, sex-, and donor source-matched controls (control A, primary immunoglobulin A nephropathy; control B, other causes; 40 recipients per group). To assess the effect of donor type, we pooled our data with two previous cohort studies where donor type had been described in detail. Results. Overall graft survival rates were 87.7% at 10 years. The overall recurrence rate of HSN was 15.4% over 10 years. Graft survival and recurrence rates in the HSN group were similar to those of control A and control B. The pooled data showed a 29.4% incidence rate for recurrent HSN. Living related donor transplantation showed a trend of higher recurrence compared with recipients with nonrelated grafts, although it was marginally significant (P=0.059). However, the graft survival rate in related-donor recipients was not inferior to that in the unrelated-donor recipients. Conclusions. Long-term graft survival and recurrence rates in kidney recipients with HSN were comparable to those of recipients with primary immunoglobulin A nephropathy. The type of donor did not significantly affect long-term graft survival.

Early Nephrology Referral Reduces the Economic Costs among Patients Who Start Renal Replacement Therapy: A Prospective Cohort Study in Korea

Background The nature of cost-saving effects of early referral to a nephrologist in patients with chronic kidney disease (CKD) is not fully evaluated. We evaluated the health care costs before and after dialysis according to the referral time. Methods A total of 879 patients who were newly diagnosed as having end-stage renal disease from August 2008 to June 2011 were prospectively enrolled. The early referral (ER) group was defined as patients who were referred to a nephrologist more than a year before dialysis and had visited a nephrology clinic 2 or more times. Patients whose referral time was less than a year were considered the late referral (LR) group. Information about medical costs was acquired from the claim data of the Korea Health Insurance Review and Assessment Service. Results The total medical costs during the first 12 months after the initiation of dialysis were not different between the 526 ER patients and the 353 LR patients. However, the costs of the ER patients during the first month were significantly lower than those of the LR patients (ER vs. LR: 3029±2219 vs. 3438±2821 US dollars [USD], P = 0.025). The total 12-month health care costs before the initiation of dialysis were significantly lower in the ER group (ER vs. LR: 6206±5873 vs. 8610±7820 USD, P<0.001). In the multivariate analysis, ER significantly lowered the health care costs during the 12 months before (2534.0±436.2 USD, P<0.001) and the first month (428.5±172.3 USD, P = 0.013) after the initiation of dialysis. Conclusions The ER of patients with CKD to a nephrologist is associated with decreased medical costs during the pretreatment period of renal replacement therapy and the early period of dialysis initiation.