The Impact of Obesity on Kidney Disease: Observational Cohort Study Analyzing 14,492 Kidney Biopsy Cases.

BACKGROUND: The obesity epidemic is associated with the emergence of new kidney diseases including obesity-related glomerulopathy (ORG) and metabolic syndrome-associated disorders. However, the effects of obesity on prevalence and outcome of biopsy-proven kidney disease are not well known. METHODS: We analyzed 14,492 kidney biopsies in 18 hospitals from 1979 to 2018 in Korea. Obesity was defined as a body mass index value of ≥ 30 kg/m². RESULTS: The most common disease was IgA nephropathy (IgAN) in both obese and non-obese participants (33.7% vs. 38.9%). Obesity was associated with a higher risk of focal segmental glomerulosclerosis (FSGS) and hypertensive nephropathy (HT-N) (odds ratio [OR], 1.72, 95% confidence interval [CI], 1.37-2.17; OR, 1.96, 95% CI, 1.21-3.19) and a lower risk of IgAN (OR, 0.74, 95% CI, 0.62-0.88). During the median follow up of 93.1 ± 88.7 months, obesity increased the risk of end-stage kidney disease (ESKD) in patients with IgAN (relative risk [RR], 1.49, 95% CI, 1.01-2.20) and lupus nephritis (LN) (RR, 3.43, 95% CI, 1.36-8.67). Of 947 obese individuals, ORG was detected in 298 (31.5%), and 230 participants had other kidney diseases, most commonly, IgAN (40.9%) followed by diabetic nephropathy (15.2%). Participants with ORG, when combined with other renal diseases, showed higher risks for developing ESKD compared to those with ORG alone (RR, 2.48, 95% CI, 1.09-5.64). CONCLUSION: Obesity is associated with an increased risk of FSGS and HT-N, and also increase the ESKD risk in IgAN and LN patients. ORG in obese participants may have favorable renal outcomes if it occurs alone without any other renal disease.

Smoking amplifies the risk of albuminuria in individuals with high sodium intake: the Korea National Health and Nutrition Examination Survey (KNHANES) 2008-2011 and 2014-2018.

Background: Smoking and sodium intake (SI) have been evaluated as risk factors for kidney disease; however, the data are inconsistent. We assessed the association between SI and cotinine-verified smoking status and the risk of albuminuria. Methods: An observational study using the Korea National Health and Nutrition Examination Survey (2008-2011 and 2014-2018) was performed. We included 37,410 adults with an estimated glomerular filtration rate of ≥60 mL/min/1.73 m2 . The smoking status was assumed based on the urine cotinine/creatinine ratio (Ucot/Ucrea). SI was estimated from spot urine sodium using the Kawasaki formula. Results: Ucot/Ucrea levels were significantly higher in current smokers (920.22 ± 9.00 ng/mg) than in ex-smokers and nonsmokers (48.31 ± 2.47 and 23.84 ± 1.30 ng/mg) (p < 0.001). Ucot/Ucrea levels were significantly higher in second-hand smokers than in participants without a history of smoking (p < 0.001). Ucot/ Ucrea levels were positively associated with SI (p for trend < 0.001). Smoking status was not associated with albuminuria. SI had a linear relationship with albuminuria (p < 0.001). In groups with the highest Ucot/Ucrea levels, the highest SI quartile indicated a significantly higher risk of albuminuria than that in the lowest quartile (risk ratio, 2.22; 95% confidence interval, 1.26-3.92; p = 0.006). The risk of albuminuria was not significant in groups with the lowest and middle tertile adjusted for multiple risk factors. Conclusion: Smokers consume higher dietary sodium and dietary SI was positively related to the risk of albuminuria. Smoking is not associated with albuminuria as a single factor. The risk of albuminuria is the higher in participants with smoking and high SI.

Characteristics and management of thrombotic microangiopathy in kidney transplantation.

Thrombotic microangiopathy is not a rare complication of kidney transplantation and is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury with extensive thrombosis of the arterioles and capillaries. Various factors can cause thrombotic microangiopathy after kidney transplantation, including surgery, warm and cold ischemia-reperfusion injury, exposure to immunosuppressants, infection, and rejection. Many recent studies on atypical hemolytic uremic syndrome have described genetic abnormalities related to excessive activation of the alternative complement pathway. The affected patients' genetic backgrounds revealed significant genetic heterogeneity in several genes involved in complement regulation, including the complement factor H, complement factor H-related proteins, complement factor I, complement factor B, complement component 3, and CD46 genes in the alternative complement pathway. Although clinical studies have provided a better understanding of the pathogenesis of diseases, the diverse triggers present in the transplant environment can lead to thrombotic microangiopathy, along with various genetic predispositions, and it is difficult to identify the genetic background in various clinical conditions. Given the poor prognosis of posttransplant thrombotic microangiopathy, further research is necessary to improve the diagnosis and treatment protocols based on risk factors or genetic predisposition, and to develop new therapeutic agents.

Role of the Circadian Clock and Effect of Time-Restricted Feeding in Adenine-Induced Chronic Kidney Disease.

Most physiological functions exhibit circadian rhythmicity that is partly regulated by the molecular circadian clock. Herein, we investigated the relationship between the circadian clock and chronic kidney disease (CKD). The role of the clock gene in adenine-induced CKD and the mechanisms of interaction were investigated in mice in which Bmal1, the master regulator of the clock gene, was knocked out, and Bmal1 knockout (KO) tubule cells. We also determined whether the renoprotective effect of time-restricted feeding (TRF), a dietary strategy to enhance circadian rhythm, is clock gene-dependent. The mice with CKD showed altered expression of the core clock genes with a loss of diurnal variations in renal functions and key tubular transporter gene expression. Bmal1 KO mice developed more severe fibrosis, and transcriptome profiling followed by gene ontology analysis suggested that genes associated with the cell cycle, inflammation, and fatty acid oxidation pathways were significantly affected in the mutant mice. Tubule-specific deletion of BMAL1 in HK-2 cells by CRISPR/Cas9 led to upregulation of p21 and tumor necrosis α and exacerbated epithelial-mesenchymal transition-related gene expression upon transforming growth factor ß stimulation. Finally, TRF in the mice with CKD partially restored the disrupted oscillation of the kidney clock genes, accompanied by improved cell cycle arrest and inflammation, leading to decreased fibrosis. However, the renoprotective effect of TRF was abolished in Bmal1 KO mice, suggesting that TRF is partially dependent on the clock gene. Our data demonstrate that the molecular clock system plays an important role in CKD via cell cycle regulation and inflammation. Understanding the role of the circadian clock in kidney diseases can be a new research field for developing novel therapeutic targets.

Perturbation of Circadian Rhythm Is Associated with Increased Prevalence of Chronic Kidney Disease: Results of the Korean Nationwide Population-Based Survey.

Disturbances in circadian rhythms cause several health problems, such as psychosis, metabolic syndrome, and cancer; however, their effect on kidney disease remains unclear. This study aimed to evaluate the association between chronic kidney disease (CKD) and sleep disturbance in a Korean adult population. A total of 17,408 participants who completed the National Health and Nutrition Examination Survey from 2016 to 2018 were assessed for their sleep patterns and renal function. CKD was defined as an estimated glomerular filtration rate ≤ 60 mL/min/1.73 m² or a positive dipstick urinalysis. Sleep onset time and sleep duration showed significant differences between the control and CKD groups (p < 0.001). After adjusting for the covariates, sleep onset time rather than sleep duration was independently associated with incidence of CKD, and this association was more significant in people who were older, in women, and in those with low body mass index and no comorbidities. When comparing the prevalence of newly diagnosed CKD according to sleep onset time in a population with no CKD risk factors or no history of CKD, the early bedtime group showed an independent association with incidence of new CKD (odds ratio (OR), 1.535; 95% confidence interval (CI), 1.011−2.330) even after adjusting for covariates. Impaired circadian rhythm along with sleep disturbance could be associated with CKD development; therefore, sleep disturbance might be an important therapeutic target for CKD.

Impact of acute kidney injury on long-term adverse outcomes in obstructive uropathy.

Obstructive uropathy is known to be associated with acute kidney injury (AKI). This study aimed to investigate the etiologies, clinical characteristics, consequences and also assess the impact of AKI on long-term outcomes. This multicenter, retrospective study of 1683 patients with obstructive uropathy who underwent percutaneous nephrostomy (PCN) analyzed clinical characteristics, outcomes including progression to end-stage kidney disease (ESKD), overall mortality, and the impact of AKI on long-term outcomes. Obstructive uropathy in adults was most commonly caused by malignancy, urolithiasis, and other causes. AKI was present in 78% of the patients and was independently associated with preexisting chronic kidney disease (CKD). Short-term recovery was achieved in 56.78% after the relief of obstruction. ESKD progression rate was 4.4% in urolithiasis and 6.8% in other causes and older age, preexisting CKD, and stage 3 AKI were independent factors of progression. The mortality rate (34%) was highly attributed to malignant obstruction (52%) stage 3 AKI was also an independent predictor of mortality in non-malignant obstruction. AKI is a frequent complication of adult obstructive uropathy. AKI negatively affects long-term kidney outcomes and survival in non-malignant obstructions. A better understanding of the epidemiology and prognostic factors is needed for adult obstructive uropathy.

Long-term Renal Outcome of Biopsy-proven Acute Tubular Necrosis and Acute Interstitial Nephritis.

BACKGROUND: Although emerging evidence suggest acute kidney injury (AKI) progress to chronic kidney disease (CKD), long-term renal outcome of AKI still remains unclear. Acute tubular necrosis (ATN) is the most common cause of AKI due to ischemia, toxin or sepsis. Acute interstitial nephritis (AIN), caused by drugs or autoimmune diseases is also increasingly recognized as an important cause of AKI. Unlike glomerular diseases, AKI is usually diagnosed in the clinical context without kidney biopsies, and lack of histology might contribute to this uncertainty. METHODS: Among 8,769 biopsy series, 253 adults who were histologically diagnosed with ATN and AIN from 1982 to 2018 at five university hospitals were included. Demographic and pathological features that are associated with the development of end stage renal disease (ESRD) were also examined. RESULTS: Rate of non-recovery of renal function at 6 month was significantly higher in the AIN (ATN vs AIN 49.3 vs 69.4%, P = 0.007) with a 2.71-fold higher risk of non- recovery compared to ATN (95% confidence interval [CI], 1.20-6.47). During the mean follow up of 76.5 ± 91.9 months, ESRD developed in 39.4% of patients with AIN, and 21.5% patients of ATN. The risk of ESRD was significantly higher in AIN (23.05; 95% CI, 2.42-219.53) and also in ATN (12.14; 95% CI, 1.19-24.24) compared to control with non-specific pathology. Older age, female gender, renal function at the time of biopsy and at 6 months, proteinuria and pathological features including interstitial inflammation and fibrosis, tubulitis, vascular lesion were significantly associated with progression to ESRD. CONCLUSION: Our study demonstrated that patients with biopsy proven ATN and AIN are at high risk of developing ESRD. AIN showed higher rate of non-renal recovery at 6 month than ATN.

M2 macrophages predict worse long-term outcomes in human acute tubular necrosis.

Although macrophages are important players in the injury/repair processes in animal models of acute kidney injury (AKI), their roles in human AKI remains uncertain owing to a paucity of human biopsy studies. We investigated the role of macrophages in 72 cases of biopsy-proven acute tubular necrosis (ATN) and six cases of healthy kidney. Macrophages were identified by CD68 and CD163 immunohistochemistry and analyzed for their effect on renal outcomes. CD163+ M2 macrophages outnumbered CD68+ cells in the healthy kidneys, suggesting that CD163+ macrophages are resident macrophages. The infiltration of both subtypes of macrophages increased significantly in ATN. The density of the CD68+ macrophages was significantly higher in advanced-stage AKI, whereas CD163+ M2 macrophages was not. Eighty percent of patients exhibited renal functional recovery during follow-up. Older age and a higher density of CD163+ macrophages predicted non-recovery, whereas the AKI stage, tubular injury score, and density of CD68+ cells did not. The density of CD163+ M2 macrophages was an independent predictor of low eGFR at 3 months in advanced-stage AKI. This is the first human study demonstrating the possible role of macrophages in the injury and repair phases of AKI.

Consensus regarding diagnosis and management of atypical hemolytic uremic syndrome.

Thrombotic microangiopathy (TMA) is defined by specific clinical characteristics, including microangiopathic hemolytic anemia, thrombocytopenia, and pathologic evidence of endothelial cell damage, as well as the resulting ischemic end-organ injuries. A variety of clinical scenarios have features of TMA, including infection, pregnancy, malignancy, autoimmune disease, and medications. These overlapping manifestations hamper differential diagnosis of the underlying pathogenesis, despite recent advances in understanding the mechanisms of several types of TMA syndrome. Atypical hemolytic uremic syndrome (aHUS) is caused by a genetic or acquired defect in regulation of the alternative complement pathway. It is important to consider the possibility of aHUS in all patients who exhibit TMA with triggering conditions because of the incomplete genetic penetrance of aHUS. Therapeutic strategies for aHUS are based on functional restoration of the complement system. Eculizumab, a monoclonal antibody against the terminal complement component 5 inhibitor, yields good outcomes that include prevention of organ damage and premature death. However, there remain unresolved challenges in terms of treatment duration, cost, and infectious complications. A consensus regarding diagnosis and management of TMA syndrome would enhance understanding of the disease and enable treatment decision-making.

Impact of aging on transition of acute kidney injury to chronic kidney disease.

Acute kidney injury (AKI) increases the risk of end stage renal disease among the elderly, but the precise underlying mechanism is unknown. We investigated the effects of aging on AKI-to-chronic kidney disease (CKD) transition, focusing on renal inflammation. Aged and young C57BL/6 mice were subjected to bilateral ischemia-reperfusion injury (IRI). Baseline proinflammatory cytokine levels of kidneys were elevated in aged mice. After IRI, aged mice also showed persistent M1 dominant inflammation, with increased proinflammatory cytokines during the recovery phase. Persistent M1 inflammation was associated with blunted activation of CSF-1/IRF4 signal for M1/M2 polarization, but in vitro macrophage polarization with cytokine stimulation was not different between young and aged mononuclear cells. The tubular expressions of cell cycle arrest markers increased in aged mice during recovery phase, and in vitro transwell experiments showed that mononuclear cells or M1 macrophages co-cultured with arrested proximal tubular cells at G1 phase significantly impaired M2 polarization, suggesting that prolonged G1 arrest might be involved in persistent M1 inflammation in aged mice. Finally, M1 dominant inflammation in aged mice resulted in fibrosis progression. Our data show that impaired M2 polarization partially driven by senescent tubule cells with cell-cycle arrest may lead to an accelerated progression to CKD in the elderly.

Role of biomarkers as predictors of acute kidney injury and mortality in decompensated cirrhosis.

Evidence suggests that novel biomarkers predict acute kidney injury (AKI) development and outcome earlier than serum creatinine. The aim of this study was to determine the incidence and prognosis of AKI in decompensated cirrhotic patients, and also assess the usefulness of plasma cystatin C, urine neutrophil gelatinase associated lipocalin (NGAL), tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) in early prediction of AKI and mortality. Single-center, prospective observational study enrolling decompensated cirrhotic patients without AKI at the time of admission. Of 111 patients with decompensated cirrhosis, 45 (40.5%) developed AKI while hospitalized. Even with 53.3% being transient (stage 1), mortality was significantly higher in AKI than non-AKI patients (46.5% vs. 25%, p = 0.02). Plasma cystatin C and urine NGAL, but not urine [TIMP-2]·[IGFBP7] at the time of admission were found to be independent early predictors of AKI. Substitution of cystatin C for creatinine significantly improved the model for end-stage liver disease (MELD) score accuracy for mortality prediction. The incidence of AKI is high and is associated with high mortality in decompensated cirrhotic patients. Plasma cystatin C and urine NGAL are useful for early detection of AKI. MELD-cystatin C, rather than original MELD, improves predictive accuracy of mortality.

Impact of Donor Age on the Outcomes of Kidney Transplantation From Deceased Donors With Histologic Acute Kidney Injury.

PURPOSE: Kidney transplantation from elderly donors with acute kidney injury (AKI) has increased recently due to donor shortage, but the safety and prognosis are not well known. We examined the effect of donor age on the outcomes of kidney transplantation (KT) from donors with histologic AKI. MATERIALS AND METHODS: We retrospectively analyzed the medical records of 59 deceased-donor KTs with acute tubular necrosis (ATN) on preimplantation donor kidney biopsy between March 2012 and October 2017. Histologic evaluations of ATN, inflammation, glomerulosclerosis (GS), interstitial fibrosis, tubular atrophy, and arterial sclerosis were performed. RESULTS: Twenty and 39 recipients received kidneys from elderly (> 60, 68.9 ± 5.0 years) and young (≤ 60, 45.9 ± 9.6 years) donors with ATN, respectively. Among the elderly donors, significantly increased donor creatinine was observed in only 44% donors, and there were more diabetic patients and women and a higher proportion of GS than among the young donors. Six months after KT, estimated glomerular filtration rate was significantly lower in recipients who received kidneys from elderly donors compared to young donors. Donor creatinine level and AKI severity did not significantly affect the recipient outcomes in either group. However, the presence of ATN and GS were significant factors that exacerbated renal outcomes after KT from elderly donors only. On multivariate analysis, severe ATN was the strongest independent predictor of elderly recipient renal function. CONCLUSIONS: Histologic injury may predict renal outcomes in KT from elderly donors. A donor allocation protocol including preimplantation renal histology should be established for KT from elderly donors.

Combination of Glomerular C4d and Morphologic Glomerular Lesions as a Possible Indicator in the Diagnosis of Acute or Chronic Active Antibody-Mediated Rejection.

BACKGROUND: Linear C4d staining in the peritubular capillaries is considered a sensitive and useful marker of active or chronic active antibody-mediated rejection (ABMR) in transplanted kidneys. However, the diagnostic significance of glomerular C4d deposits (gC4d) is still undetermined. The aim of this study is to evaluate the association of gC4d with clinicopathologic features and to assess its diagnostic value. METHODS: From 2013 to 2018, a total of 158 cases of allograft kidney biopsy specimens were obtained from the Korea University Anam Hospital. The histologic features were evaluated according to the Banff classification. The gC4d were determined through immunohistochemical analyses and classified based on scores of 0 to 3 according to the extent of gC4d. RESULTS: A total of 73 cases (46.2%) showed gC4d, and 37 cases (23.4%), 23 cases (14.6%), and 13 cases (8.2%) were classified with a score of 1+, 2+, and 3+, respectively. The gC4d showed a significant correlation with antibody-associated histologic lesions, including peritubular capillaritis, glomerulitis, and transplant glomerulopathy (P < .001). However, gC4d showed no significant association with cell-mediated injuries such as tubulitis, interstitial inflammation, acute tubular necrosis, and thrombotic microangiopathy. Although positive gC4d alone was associated with nonspecific findings without ABMR, most cases of gC4d combined with glomerulitis or transplant glomerulopathy showed typical histologic features of ABMR, clinically with higher antibody titers and severe functional deterioration. CONCLUSIONS: Glomerular C4d deposits may be an alternate useful marker in the diagnosis of active or chronic active ABMR when combined with histologic features of glomerular lesions.

Diastolic dysfunction and acute kidney injury in elderly patients with femoral neck fracture.

BACKGROUND: Femoral neck fracture is common in the elderly population. Acute kidney injury (AKI) is an important risk factor for mortality in patients who have had such fracture. We evaluated the incidence of AKI in patients who had femoral neck fracture and identified risk factors for AKI and mortality. METHODS: This was an observational cohort study including 285 patients who were ≥ 65 years of age and who underwent femoral neck fracture surgery between 2013 and 2017. RESULTS: The mean age was 78.63 ± 6.75 years. A total of 67 (23.5%) patients developed AKI during the hospital stay: 57 (85.1%), 5 (7.5%), and 5 (7.5%) patients were classified as having stage 1, 2, and 3 AKI, respectively. Patients with AKI had a lower baseline estimated glomerular filtration rate and higher left atrial dimension, left ventricular mass index, pulmonary artery pressure, and the ratio of early mitral inflow velocity to early diastolic mitral annulus velocity (E/e') and were more likely to have diabetes or hypertension (HTN) (P < 0.05). The presence of HTN (odds ratio [OR], 4.570; 95% confidence interval [CI], 1.632-12.797) higher E/e' (OR, 1.105; 95% CI, 1.019-1.198), and lower hemoglobin (OR, 0.704; 95% CI, 0.528-0.938) were independently associated with a higher risk for developing AKI. Severe AKI (OR, 24.743; 95% CI, 2.822-212.401) was associated with a higher risk of mortality. CONCLUSION: Elderly patients with femoral neck fracture had a high incidence of AKI. Diastolic dysfunction was associated with AKI. Severe AKI was associated with in-hospital mortality.

The Impact of Preexisting Chronic Kidney Disease on the Severity and Recovery of Acute Kidney Injury.

BACKGROUND: Recent observational studies have shown that in chronic kidney disease (CKD) patients, a significantly smaller percentage of patients with an episode of acute kidney injury (AKI) have full recovery of renal function compared to those without CKD. However, precise mechanisms involved in the incomplete repair after AKI with preexisting CKD have not been completely ascertained. Here, we assessed the impact of preexisting CKD on the severity and recovery of AKI in a mouse model of 5/6 nephrectomy. METHODS: Male CD-1 mice underwent 5/6 nephrectomy (Nx). Six weeks post surgery, ischemia reperfusion injury (IRI) or a sham operation was performed and functional, histological, and various molecular parameters were compared between them. RESULTS: Serum creatinine level on day 1 after IRI was comparable between control and Nx mice. However, serum creatinine remained significantly higher throughout the recovery phase in Nx mice compared to control mice. mRNA and protein expression of the cell cycle regulatory proteins were persistently elevated in Nx mice and this was associated with significantly increased levels of the G1 cell cycle arrest markers. Treatment with a p53 inhibitor following IRI resulted in not only decreased expression of G1 arrest markers but also decreased fibrosis, suggesting that prolonged epithelial G1 cell cycle arrest might be partially responsible for impaired recovery from superimposed AKI on CKD. CONCLUSION: Taken together, reduced nephron mass have a negative effect on the repair process that is partially mediated by the disruption of the cell cycle regulation.

Predictive factors of acute kidney injury in patients undergoing rectal surgery.

BACKGROUND: Despite major advance in surgical techniques from open surgery to robot-assisted surgery, acute kidney injury (AKI) is still major postoperative complication in rectal surgery. The purpose of this study is to compare the incidence of postoperative AKI according to different surgical techniques and also the risk factors, outcomes of AKI in patients undergoing rectal cancer surgery. METHODS: A retrospective medical chart review was done in a total of 288 patients who received proctectomy because of rectal cancer from 2011 to 2013. RESULTS: The mean patient age was 62 ± 12 years, and male was 64.2%. Preoperative creatinine was 0.91 ± 0.18 mg/dL. Open surgery was performed in 9%, and laparoscopy assisted surgery or robot assisted surgery were performed in 54.8% or 36.1% of patients, respectively. AKI developed in 11 patients (3.82%), 2 (18%) of them received acute hemodialysis. Incidence of AKI was not different according to the surgical technique, however, the presence of diabetes, intraoperative shock, and postoperative ileus was associated with the development of AKI. In addition, AKI patients showed significantly longer hospital stay and higher mortality than non-AKI patients. CONCLUSION: Our study demonstrated that despite advances in surgical techniques, incidence of postoperative AKI remains unchanged and also that postoperative AKI is associated with poor outcome. We also found that presence of diabetes, intraoperative shock and postoperative ileus are strongly associated with the development of AKI. More careful attention should be paid on high risk patients for the development of postoperative AKI regardless of surgical techniques.

Polyethylene glycol plus ascorbic acid for bowel preparation in chronic kidney disease.

The safety of polyethylene glycol plus ascorbic acid has not been fully investigated in patients with renal insufficiency. High-dose ascorbic acid could induce hyperoxaluria, thereby causing tubule-interstitial nephritis and renal failure. This study aims to evaluate the safety and efficacy of polyethylene glycol plus ascorbic acid in patients with chronic kidney disease.We retrospectively reviewed prospectively collected data on colonoscopy in patients with impaired renal function. Patients were divided into 2 groups: 2 L polyethylene glycol plus ascorbic acid (n = 61) and 4 L polyethylene glycol (n = 80). The safety of the 2 groups was compared by assessing the differences in laboratory findings before and after bowel cleansing.The laboratory findings were not significantly different before and after the administration of 2 L polyethylene glycol plus ascorbic acid or 4 L polyethylene glycol. In both groups, the estimated glomerular filtration rate was not influenced by the administration of the bowel-cleansing agent. Patients' reports on tolerance and acceptability were better in the 2 L polyethylene glycol plus ascorbic acid group than in the 4 L polyethylene glycol group.The 2 L polyethylene glycol plus ascorbic acid solution is a safe choice for bowel preparation before colonoscopy in patients with impaired renal function.

The Role of M2 Macrophages in the Progression of Chronic Kidney Disease following Acute Kidney Injury.

INTRODUCTION: Acute kidney injury (AKI) is a major risk factor in the development of chronic kidney disease (CKD). However, the mechanisms linking AKI to CKD remain unclear. We examined the alteration of macrophage phenotypes during an extended recovery period following ischemia/reperfusion injury (IRI) and determine their roles in the development of fibrosis. METHODS: The left renal pedicle of mice was clamped for 40 min. To deplete monocyte/macrophage, liposome clodronate was injected or CD11b-DTR and CD11c-DTR transgenic mice were used. RESULTS: Throughout the phase of IRI recovery, M2-phenotype macrophages made up the predominant macrophage subset. On day 28, renal fibrosis was clearly shown with increased type IV collagen and TGF-ß. The depletion of macrophages induced by the liposome clodronate injection improved renal fibrosis with a reduction of kidney IL-6, type IV collagen, and TGF-ß levels. Additionally, the adoptive transfer of the M2c macrophages partially reversed the beneficial effect of macrophage depletion, whereas the adoptive transfer of the M1 macrophages did not. M2 macrophages isolated from the kidneys during the recovery phase expressed 2.5 fold higher levels of TGF-ß than the M1 macrophages. The injection of the diphtheria toxin into CD11b or CD11c-DTR transgenic mice resulted in lesser depletion or no change in M2 macrophages and had little impact on renal fibrosis. CONCLUSION: Although M2 macrophages are known to be indispensible for short-term recovery, they are thought to be main culprit in the development of renal fibrosis following IRI.

Renal Klotho expression in patients with acute kidney injury is associated with the severity of the injury.

BACKGROUND/AIMS: The potential physiologic roles of Klotho in acute kidney injury (AKI) have recently been demonstrated in animal models. However, to date, there have been no human studies investigating the expression of renal Klotho in AKI. METHODS: We retrospectively collected biopsy specimens and clinical data of AKI patients between January 2001 and December 2012. Klotho expression was determined by immunohistochemical staining, and the clinical-pathological correlation was examined. RESULTS: Among the 34 patients diagnosed with acute tubular necrosis or acute tubulointerstitial nephritis, 21 patients without chronic histological lesions were included. The mean age was 37.3 ± 18.5 years and the mean peak creatinine level was 8.2 ± 5.5 mg/dL. In total, 10 patients (47.6%) received temporary renal replacement therapy (RRT); however, 17 patients (81%) showed functional recovery with creatinine levels of < 1.3 mg/dL after 1 month. The intensity of Klotho expression was scored as a percentage of Klotho-positive area. The renal Klotho score showed a significant negative correlation with the initial or peak creatinine level. When the patients were divided into three groups according to the Klotho score (low, middle, high), the low group had a significantly higher peak creatinine level and a more frequent requirement for RRT. However, the Klotho score was not a significant predictor of renal recovery. CONCLUSIONS: The results demonstrated that renal Klotho expression in humans decreased significantly according to the severity of AKI, regardless of the etiology, and that low expression was associated with a poor short-term outcome.

The incidence and risk factors of acute kidney injury after hepatobiliary surgery: a prospective observational study.

BACKGROUND: Although intraperitoneal surgery is a major operation associated with postoperative acute kidney injury (AKI), the incidence, risk factors, and long-term renal outcome are not well known. We aimed to determine the risk factors and 6 months renal outcome in patients with clinical or subclinical AKI after hepatobiliary surgery. We also assessed the validity of urine neutrophil gelatinase-associated lipocalin (NGAL) in the early detection of AKI or prediction of renal outcome. METHODS: This prospective observational study enrolled patients with normal renal function who underwent hepatobiliary surgeries. Urine and serum samples were collected for NGAL measurement. RESULTS: Among 131 patients, 10 (7.6%) developed postoperative AKI. Urine NGAL at 12 h postsurgery was the most predictive parameter for the diagnosis of AKI (cutoff, 92.85 ng/mL). With the cutoff value, subclinical AKI was diagnosed in 42 (32.1%) patients. Patients with clinical AKI and those with subclinical AKI were assigned to the AKI group. The AKI group had significantly higher model for end-stage liver disease and sodium (MELD-Na) score, lower albumin level, and longer hospital stay after surgery than the non-AKI group. Older age and higher MELD-Na score were independent risk factors for the development of postoperative AKI. At 6 months postsurgery, the estimated glomerular filtration rate (eGFR) in the AKI group was significantly lower than that in the non-AKI group, although the baseline eGFR was not different. In multiple linear regression analysis, the maximum urine NGAL level during 24 h postsurgery, intraoperative fluid balance, and having liver transplantation were significantly associated with a poor 6 months renal outcome. CONCLUSION: Urine NGAL was useful in the early diagnosis of postoperative AKI as well as in predicting the 6 months renal outcome after hepatobiliary surgery. A considerable proportion of patients developed subclinical AKI, and these patients showed worse renal outcome compared with the non-AKI group.