Correlation of Plasma Klotho Levels and Carotid Intima- Media Thickness in CKD Patients on Regular Hemodialysis

Background: The incidence of heart death is 5-10 times more in patients with chronic kidney disease (CKD) with regular hemodialysis compared to the general population. Vascular calcification is a risk factor. In CKD patients there is a decrease in the distal renal cell cells which are the main producer of Klotho in the body. The functions of Klotho are maintaining integrity, endothelial permeability and endogenous inhibitors of vascular calcification. Previous studies reported an association between vascular calcification and Klotho plasma levels. Vascular calcification for heart disease can be determined by the thickness Intima Media (TIM) Carotid Artery. Objective: To determine the correlation of plasma Klotho levels with the Intima Media thickness of the Carotid Artery in CKD patients with regular hemodialysis. Methode: This cross-sectional study was conducted at the Rasyida Kidney General Hospital in Medan from April to July 2018. Patients with CKD who have undergone routine hemodialysis are examined for plasma levels of Klotho and real time ultrasound examinations to determine the thickness of arterial intima media carotid. Data are analyzed with Mann Whitney test, binominal logistic regression and Pearson correlation. Results: Seventy patients with CKD showed an average plasma Klotho level of 281.43 + 298.63 pg / ml with an average TIM of the carotid artery of 0.22 + 0.09 cm. Patients were divided into 2 groups, namely the calcification group (n = 39) and the noncalcified group (n = 31). Mann-Whitney test was performed with the results that there were differences in plasma Klotho levels between the calcification group and the noncalcified carotid artery group which were statistically significant (p = 0.001). The binominal logistic regression analysis test was performed on risk factors associated with the incidence of vascular calcification and the results of Klotho serum levels, Diabetes Mellitus and Hypertension were found to be significant risk factors for calcification (p <0.05). With the Pearson correlation test, the negative correlation of plasma Klotho levels with the thickening of Intima Carotid Arterial Media was statistically significant with moderate correlation strength (p = 0.002; r = -0.368). Conclusion: Patients with chronic kidney disease with low plasma Klotho levels have thickening of the intima media of carotid artery.

Unilateral Ureteral Obstruction as a Model of Kidney Fibrosis and Increasing of Systolic Blood Pressure in Mice

Background: Obstructive nephropathy can lead to progressive and permanent loss of kidney function characterized by interstitial inflammation and tubulointerstitial fibrosis. Tubulointerstitial fibrosis presents as the end result of various kidney injuries in general and can cause chronic kidney disease (CKD), which can progress to end-stage kidney disease and hypertension. Objective: This study aimed to determine the effectiveness of unilateral ureteral obstruction (UUO) as a model of renal fibrosis and hypertension. Method: Sixteen male Rattus norvegicus mice (150-200 g) were divided into control groups and UUO by ureteral ligation, eight mice each. The systolic blood pressure (SBP) were measured every seven days. After 30 days the animals were dissected to analyze the changes in renal interstitial fibrosis. Statistical analysis was carried out by unpaired t test or alternative test. Results: There was a significant increase in interstitial fibrosis in the UUO rat group [1% (0% - 5%) vs. 75% (20% - ­90%), p <0.001] and SBP [85.38 ± 1.69 mmHg vs 144.75 ± 4.27 mmHg, p <0.001]. Conclusion: UUO can be used as a model of fibrosis and hypertension, which can be used as the basis for the development of anti-fibrotic and anti-hypertensive drugs.

Plasma Neutrophil Gelatinase-Associated Lipocalin (NGAL) and Creatinine Levels after Percutaneous Coronary Intervention

Background. Contrast-induced nephropathy (CIN) is defined as an increase in serum creatinine ≥ 25% or ≥0.3 mg/dl in 48 hours after the administration of a contrast agent in the absence of other causative factors (KDIGO 2012). Neutrophil Gelatinase-Associated Lipocalin (NGAL) is a substance produced by the kidneys in acute kidney injury (AKI) caused by various insults from ischemia to toxin-induced nephropathy. NGAL is known to increase earlier than serum creatinine level. NGAL is also a protease-resistant polypetide; it is released from the distal tubule, secreted to the urine or returned to the plasma (back leak), freely filtered in the glomerulus, reabsorbed in the proximal tubule through the megalin receptor endocytosis or secreted to urine. This makes NGAL detectable both in the blood and urine. Aim. To elucidate the effect of contrast administration to serum NGAL and serum creatinine levels with in patients undergoing PCI. Methods. The study was done in the Cardiovascular Care ward in M. Djamil General Hospital, Padang, West Sumatra, Indonesia. Through consecutive random sampling, 21 subjects were selected. The subjects’ serum NGAL and creatinine levels were acquired before PCI and 6 hours after contrast administration. Results. The mean serum NGAL and creatinine levels of the subjects before and after contrast administration were 52.26 ng/ml vs 64.78 ng/ml and 1.1 mg/dl vs 1.09 mg/dl, respectively. The serum NGAL level difference before and after contrast administration was statistically significant (p=0.003) whereas the serum creatinine level was not (p>0.005). Conclusion. There is an increase of serum NGAL levels before and after contrast administration in patient undergoing PCI, whereas serum creatinine level was not. Future studies should elaborate on the use of NGAL as an early diagnostic marker for CIN.

Histopathology Interstitial Severity Index Associated with Glomerular and Tubular Severity Index in Nephrotic Syndrome Patients

Introduction: Nephrotic syndrome is characterized by massive proteinuria due to leakage of glomerular basal membrane, and subsequent process in tubular and interstitial tissue. It should be elucidated whether the severity of histopathological lesions in compartments of kidney tissue play a role and whether lesion in those compartments associated one to another. Aim: The study aims to correlate severity histopathologic lesions among compartments in kidney tissue. Method: All patients with nephrotic syndrome were biopsied and the cores were stained with Hematoxylin-Eosin, PAS, Masson’s Trichrome to look at glomerular, tubular, interstitial and vascular involvements. Glomerular abnormalities including mesangial hypercellularity, endocapillary hypercellularity, membranous; tubular, interstitial, and vascular severities were scored according to type, activity, severity and distribution in histopathologic features. Results: This study included 46 patients consisted of 16 (34.8%) males and 30 (65.2%) females, aged 26 ± 10 years, SBP 121.7 ± 13.10 and DBP 78.21 ± 7.80 mmHg, diagnosed with 14 lupus and 32 non-lupus nephrotic syndrome. Histopathologic abnormalities showed glomerular index was 4.26 ± 2.34, tubular index was 3.09 ± 1.90, interstitial index was 3.02 ± 1.48, vascular index was 0-3, pathologic index was 10.56 ± 4.54. There was significant correlation of severity index between interstitial and glomerular lesions (R=0.49, P=0.001), and between interstitial and tubular lesions (R=0.45, P=0.002). However, there were no significant correlations of severity index between interstitial and vascular lesions, and glomerular and tubular lesions. Conclusion: There are significant correlations of severity index between interstitial with glomerular and tubular lesions. It may implicate that histopathological process in interstitial tissue plays a central role in the pathogenesis of proteinuria in nephrotic syndrome.