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

Background

Chronic kidney disease (CKD) is a common problem in long-term survivors after liver transplantation (LT). It is important to identify and correct risk factors that negatively affect kidney function. The purpose of this study was to delineate the risk factors associated with progressive kidney dysfunction after OLT.

Methods

We analyzed 50 recipients (10 female, 40 male) of overall age of 44 ± 13 year who were all ≥18 years old and underwent first LT between 1999 and 2005. Patient-related risk factors were evaluated for renal failure at 3 and 5 years after transplantation. We evaluated parameters of demographic data, laboratory values, daily proteinuria, and renal resistive index (RRI) by Doppler ultrasonography. CKD was defined as a sustained decrease in estimated glomerular filtration rate (eGFR). Patients were divided into 3 groups according to the change in eGFR from the baseline value: group 1, stable eGFR (no change from baseline); group 2, <50% decreased eGFR; and group 3, ≥50% decrease from baseline. eGFR was calculated by using Modification of Diet in Renal Disease (MDRD) formula.

Results

At 3 years after LT, GFR negatively correlated with initial Child-Pugh score (r = −0.42; P < .01); microalbuminuria (r = −0.28; P < .01), and RRI (r = −0.36; P < .01). After 5 years, GFR negatively correlated with initial gamma glutamyl transferase (r = −0.21; P < .05), PT (r = −0.29; P < .05), and RRI (r = −0.32; P < .01). Pretransplantation direct bilirubin levels were significantly correlated with GFR decrease at 3 years (P = .05). At 5 years of follow-up, smoking (P < .05), baseline alanine aminotransferase (P = .03) and serum triglyceride (P < .01) levels significantly correlated with eGFR decrease. Pretransplantation serum creatinine levels were stratified into normal versus high groups. Patients with increased basal serum creatinine levels displayed shorter survivals than those with normal creatinine levels, namely, median values of 21 ± 3.9 months versus 14 ± 2.4 months, log rank test: P < .05).

Conclusion

Renal function after liver transplantation show sustained impairment in certain patients. In the short term the main risk factors for renal detoriation were severity of liver disease before LT, microalbuminuria, and renal perfusion. In the long term, smoking and dyslipidemia were the main predictors of CKD. Patients with high basal serum creatinine values were at increased risk of mortality.     

Two cases of preceded aortic valve replacement for severe aortic stenosis before the cancer operations

We report two cases of aortic valve replacement (AVR) for severe aortic stenosis (AS) before the cancer operations. Severe AS poses a great risk for noncardiac surgery. In the ACC/AHA 2007 Guideline on Perioperative Cardiovascular Evaluation and Care for Noncardiac Surgery, if the AS is symptomatic, elective noncardiac surgery should generally be postponed or canceled. Such patients require AVR before elective noncardiac surgery. On the other hand, in patients with severe AS who refuse cardiac surgery, noncardiac surgery can be performed with a mortality risk of approximately 10%. In our cases, severe AS was found in the preoperative examination. We informed them about necessary AVR before noncardiac surgery, and patients consented to our suggestion. AVR was performed around 7 days after this consent, and cancer operation was performed around 30 days after the AVR. However, there are no clear guidelines for this interval between AVR and cancer operation. In our cases the patients underwent the cardiac surgery and noncardiac surgery in a short period without serious complication in the perioperative management. It is very important to discuss among surgeon, cardiovascular surgeon, cardiologist and anesthesiologist. Especially anesthesiologist should take an important role in organizing these departments for such patients.     

Effects of atorvastatin and ezetimibe on endothelial function in dyslipidemic patients with chronic kidney disease

Backgroud

Chronic kidney disease (CKD) is a staple risk factor not only for renal failure but also for cardiovascular diseases. In addition, because dyslipidemia facilitates atherosclerosis and renal dysfunction, antihyperlipidemic treatment is important to prevent cardiac and renal events in CKD patients.

Methods

We compared the effects of a statin and an intestinal cholesterol transporter inhibitor in 20 dyslipidemic patients with CKD presenting with proteinuria and/or glomerular filtration rate <60 mL/min/1.73 m². Either 5–10 mg atorvastatin or 10 mg ezetimibe was given for 3 months each in a randomized crossover manner and the parameters of oxidative stress, inflammation and endothelial function were compared.

Results

Atorvastatin lowered serum low-density lipoprotein (LDL) cholesterol more prominently than ezetimibe (103 ± 38 vs 130 ± 45 mg/dL, p < 0.001), while serum γ-glutamyl transpeptidase was higher in atorvastatin than in ezetimibe (29 ± 16 vs 25 ± 11 U/L, p = 0.013). On the other hand, serum oxidized LDL and high-sensitivity C-reactive protein were lower in the atorvastatin treatment period than in the ezetimibe treatment period (109 ± 38 vs 146 ± 67 U/L, p = 0.002; 1.02 ± 1.46 vs 1.47 ± 1.77 µg/mL, p = 0.003). Although serum adiponectin was not significantly different between the two drugs, the reactive hyperemia index, an index of endothelial function, was higher in atorvastatin than in ezetimibe (1.94 ± 0.58 vs 1.60 ± 0.44, p = 0.023).

Conclusion

It is concluded that atorvastatin is more potent than ezetimibe in improving the serum lipid profile, reducing oxidative stress, suppressing inflammation and preserving endothelial function, while ezetimibe may be advantageous in reducing the hepatic lipid load.     

Outcomes of liver transplantation for Alagille syndrome after Kasai portoenterostomy: Alagille Syndrome with agenesis of extrahepatic bile ducts at porta hepatis

BackgroundAlagille syndrome (ALGS) is an autosomal dominant disorder, characterized by a paucity of intrahepatic bile ducts, resulting in significant cholestasis, and peculiar extrahepatic features. Some ALGS patients show a considerable overlap with biliary atresia (BA), and they can undergo Kasai procedure. The purpose of this study is to show the manifestations of BA overlapped ALGS cases in our institution, and to compare the outcomes of ALGS patients following liver transplantation (LT) between those who previously underwent Kasai surgery (ALGS-Kasai group) and those who did not (ALGS-non-Kasai group).MethodsMedical records of ALGS patients who underwent LT in Kyoto University Hospital, Japan from January 1992 to March 2018 were analyzed. ALGS diagnosis was determined according to physical, radiologic, and histopathological findings.ResultsThirty-one patients were ascertained (ALGS-Kasai: 4 males and 5 females vs. ALGS-non-Kasai: 14 males and 8 females, p = 0.43). Of 31 ALGS patients, 96.8% of children had pulmonary artery stenosis, 54.8% showed facial features, 29% revealed skeletal anomalies and 9.7% demonstrated ocular anomalies. The age at LT was significantly younger in ALGS-Kasai than ALGS-non-Kasai group (1.47 [interquartile range (IQR), 0.75–1.92] vs. 5.1 [IQR, 1.4–9.29] years; p = 0.038). Overall patient survival did not significantly differ between ALGS-Kasai (88.9%) and ALGS-non-Kasai patients (86.4%) (p = 0.84). Furthermore, the 1-year, 5-year, and 10-year patient survival rates for ALGS-Kasai group were 100%, 88.9%, and 88.9%, respectively, whereas those for ALGS-non-Kasai group were 90.9%, 90.9%, and 86.4%, respectively, with p-values of 0.36, 0.90, and 0.84, respectively.ConclusionsBA overlapped ALGS cases had neonatal progressive cholestasis which prompted Kasai procedure, and early liver dysfunction after Kasai led to performing LT. The ALGS-Kasai patients undergo LT at earlier ages than the ALGS-non-Kasai patients, however, overall patients' survival rates are similar between groups. Overall ALGS patients' survival rate after LT is considered high.Levels of EvidenceLevel III; Case–control study or Retrospective comparative study.     

The relationship between the soluble Klotho protein and the residual renal function among peritoneal dialysis patients

Background

Klotho has been investigated as an anti-aging protein that is predominantly expressed in the distal convoluted tubules in the kidneys and in the choroid plexus of the brain. The purpose of the present study was to determine the relationship between the soluble form of Klotho and renal function in chronic peritoneal dialysis (PD) patients, a relationship which remains poorly understood.

Methods

The soluble Klotho levels in the serum, urine, and peritoneal dialysate obtained from thirty-six PD patients were determined by a sandwich enzyme-linked immunosorbent assay system.

Results

The amount of urinary excreted soluble Klotho over 24?h ranged from 1.54 to 1774.4?ng/day (median 303.2?ng/day; interquartile range [IR] 84.1–498.5), while the serum soluble Klotho concentration ranged from 194.4 to 990.4?pg/ml (mean 553.7?±?210.4?pg/ml). The amount of urinary Klotho excretion was significantly correlated with residual renal function. However, there was no apparent correlation between the serum soluble Klotho levels and the residual renal function. Klotho was also detected in the 24-h dialysate collections. There was a significant correlation between the peritoneal Klotho excretion and the amount of albumin contained in the dialysate collections (r?=?0.798, p?Conclusions The total amount of urinary excreted Klotho, but not the serum level of soluble Klotho, may be a potential biomarker for assessing the residual renal function among PD patients. Whether our findings are also valid for chronic kidney disease patients overall should therefore be evaluated in greater detail.     

Skeletal Analysis of the Long Bone Abnormality (lbab/lbab) Mouse, A Novel Chondrodysplastic C-Type Natriuretic Peptide Mutant

Long bone abnormality (lbab/lbab) is a strain of dwarf mice. Recent studies revealed that the phenotype is caused by a spontaneous mutation in the Nppc gene, which encodes mouse C-type natriuretic peptide (CNP). In this study, we analyzed the chondrodysplastic skeletal phenotype of lbab/lbab mice. At birth, lbab/lbab mice are only slightly shorter than their wild-type littermates. Nevertheless, lbab/lbab mice do not undergo a growth spurt, and their final body and bone lengths are only ~60% of those of wild-type mice. Histological analysis revealed that the growth plate in lbab/lbab mice, especially the hypertrophic chondrocyte layer, was significantly thinner than in wild-type mice. Overexpression of CNP in the cartilage of lbab/lbab mice restored their thinned growth plate, followed by the complete rescue of their impaired endochondral bone growth. Furthermore, the bone volume in lbab/lbab mouse was severely decreased and was recovered by CNP overexpression. On the other hand, the thickness of the growth plate of lbab/+ mice was not different from that of wild-type mice; accordingly, impaired endochondral bone growth was not observed in lbab/+ mice. In organ culture experiments, tibial explants from fetal lbab/lbab mice were significantly shorter than those from lbab/+ mice and elongated by addition of 10⁻⁷ M CNP to the same extent as lbab/+ tibiae treated with the same dose of CNP. These results demonstrate that lbab/lbab is a novel mouse model of chondrodysplasia caused by insufficient CNP action on endochondral ossification.     

Neuromelanin-Sensitive MRI

Abstract   The basics and the technique of magnetic resonance imaging (MRI) for visualizing the neuromelanin present in dopaminergic and noradrenergic nuclei in the substantia nigra pars compacta (SNc) and locus caeruleus (LC) are introduced. Neuromelanin, a black pigment produced during catecholamine synthesis, has paramagnetic T1-shortening effects. Conventional MRI techniques fail to depict the contrast generated by neuromelanin, but neuromelanin-sensitive T1-weighted fast spin echo technique at 3 T allows the direct visualization of the SNc and LC as hyperintense areas. In Parkinson's disease, neuromelanin-related signals from the SNc and LC are diminished, suggesting neuronal degeneration in both the nuclei. In depression and schizophrenia, signals from the LC are reduced while those from the SNc are augmented, suggesting monoamine and dopamine hypotheses, respectively. Neuromelanin-sensitive MRI is a promising technique to elucidate the pathologic or functional changes in the catecholamine neurons of the brain stem that occur in degenerative and psychiatric diseases.      

Epithelial cell density in cataractous lenses of patients with diabetes: association with erythrocyte aldose reductase

In the present study we evaluated the cell density of lens epithelium and its relation to the degree of erythrocyte aldose reductase (AR) in patients with type 2 diabetes. This prospective clinical study included 46 eyes of patients with type 2 diabetes and 48 eyes of patients without diabetes mellitus (DM). Flat preparations of lens epithelial cells (LECs) attached to the anterior capsule were studied. Multiple regression analysis was performed to evaluate the association between lens cell density and age, gender, type of cataract, duration of diabetes, diabetic retinopathy (DR), the levels of glycosylated hemoglobin (HbA1c) and erythrocyte AR. The mean density of LECs of patients with type 2 diabetes was 4,141+/-508cells/mm(2), which was significantly lower than that of patients without DM (4,560+/-458cells/mm(2); p<0.0001). Multiple regression analysis revealed that the level of erythrocyte AR was correlated with the reduction of LECs in the eyes of patients with type 2 diabetes. The correlation between the density of LECs and the amount of erythrocyte AR was significant in the diabetic group with a high value of HbA1c (>6.5%) or with DR. These results suggest that the polyol pathway via AR may be associated with the reduction of epithelial cell density in the eyes of patients with DM.