Elevated Serum Blood Urea Nitrogen Research Articles

The Association between Serum Adiponectin Levels and Endothelial Function in Non-Dialysis-Dependent Chronic Kidney Disease Patients.

Adiponectin is the richest human circulating adipokine with anti-inflammatory, antioxidant, and insulin-sensitizing effects. We evaluated the association between serum adiponectin levels and endothelial function in chronic kidney disease (CKD) patients, obtaining fasting blood samples from 130 non-dialysis CKD subjects. We measured the endothelial function-represented by the vascular reactivity index (VRI)-via non-invasive digital thermal monitoring, and serum adiponectin concentrations by enzyme immunoassay kits. A total of 22 (16.9%), 39 (30.0%), and 69 (53.1%) patients had poor (VRI < 1.0), intermediate (1.0 ≤ VRI < 2.0), and good (VRI ≥ 2.0) vascular reactivity. Elevated serum blood urea nitrogen (BUN) level was negatively correlated with VRI values, but serum adiponectin and estimated glomerular filtration rate were positively associated with VRI values by univariate linear regression analysis. After applying multivariate stepwise linear regression analysis adjustment, the significantly positive association of adiponectin (p < 0.001), and the significantly negative association of log-BUN (p = 0.021) with VRI values in CKD subjects remained. In an animal study using in vitro blood-vessel myography, treatment with adiponectin enhancing acetylcholine-mediated vasorelaxation in 5/6 nephrectomy CKD mice. Our study results indicated that adiponectin concentration was positively associated with VRI values and modulated endothelial function in non-dialysis CKD patients.

A Spectrum of Biopsy - Proven Renal Disorders and Their Clinicopathological Correlation in Elderly Population From a Tertiary Care Center in South India.

IntroductionChronic kidney disease (CKD) has become a health concern with an extensive burden on incidence and prognosis. While the increasing lifespan contributes to a higher incidence of CKD among the elderly, the diagnostic picture in this age group is complicated by senescence-related changes. A better understanding of the etiology and progression of the disease warrants renal biopsy in such patients. This study aims to explore the histopathological spectrum of native renal biopsies leading to CKD in elderly patients in a tertiary care hospital.MethodsAmong the list of patients who had undergone renal biopsy at our institute from January 2015 to March 2020, elderly patients aged ≥ 60years were chosen for this study. Their demographic details, lab investigations and histopathological reports were collected. The sex distribution and prevalence of different renal diseases was calculated. The subjects were classified into four broad diagnostic groups - primary glomerular disease, diabetic nephropathy, hypertensive nephropathy, and tubulointerstitial disease. The estimated glomerular filtration rate (eGFR) values were calculated and used to stage chronic kidney disease in these patients. Statistical analysis was carried out to find a correlation between diagnostic groups and CKD presence and between serum C3 values and immunofluorescence for the same on biopsy.ResultsOne hundred thirty-two patients formed the study sample with a male to female ratio of 1.28:1, showing a slight male predominance. The most common diagnostic group was primary glomerular disease (46%), among which focal segmental glomerulosclerosis (FSGS) was the most common entity (12%). 47.7% and 66.6% of patients in the study sample showed elevated serum blood urea nitrogen (BUN) and creatinine values, respectively. 86% of our study sample had low eGFR values, and the majority (35%) of the patients were classified under CKD stage 3. CKD incidence was high among patients with primary glomerular diseases, but no significant statistical correlation was found. 43.5% of all IF positive cases showed low serum C3 values and established a positive correlation between IF and serum C3 values.ConclusionThere is no statistically significant correlation of the four diagnostic groups to the CKD. CKD in the elderly may be multifactorial, and a collaborative study across the nations may be needed to further evaluate the etiology.

Impact of Clinical, Laboratory and Fluid Therapy Variables on Hospital Length of Stay for Children with Acute Pancreatitis.

PurposeThere have been many efforts to develop generalizable severity markers in children with acute pancreatitis (AP). Expert opinion panels have developed consensus guidelines on management but it is unclear if these are sufficient or valid. Our study aims to assess the effect of clinical and laboratory variables, in addition to treatment modality on hospital length of stay (LOS) as a proxy variable for severity in pediatric patients admitted with AP.MethodsWe conducted a retrospective chart review of patients between ages of 0–18 years, who were admitted with AP at 2 institutions between 2013–2018, John R. Oishei Children's Hospital (Buffalo, NY, USA) and Medical University of South Carolina Children's Hospital (Charleston, SC, USA). We constructed three linear regression models to analyze the effect of clinical signs of organ dysfunction, laboratory markers and fluid intake on hospital LOS.ResultsNinety-two patients were included in the study. The mean age was 12 years (range, 7.6–17.4 years), 55% were females, and median LOS was 3 days. The most frequent cause of AP was idiopathic. Our study showed that elevated blood urea nitrogen (BUN) on admission (p<0.005), tachycardia that lasted for ≥48 hours (p<0.001) and need for fluid resuscitation were associated with increase LOS. Total daily fluid intake above maintenance did not have a significant effect on the primary outcome (p=0.49).ConclusionElevated serum BUN on admission, persistent tachycardia and need for fluid resuscitation were associated with increase LOS in pediatric AP. Daily total fluid intake above recommended maintenance did not reduce LOS.

Mitochondrial dysfunction and oxidative stress are involved in the mechanism of methotrexate-induced renal injury and electrolytes imbalance

Methotrexate is a folate analog used against a wide range of diseases including malignancies and autoimmune disorders. On the other hand, clinical use of the MTX is associated with kidney injury and renal failure. There is no clear mechanism for MTX-induced renal injury. The current investigation was designed to evaluate the role of mitochondrial dysfunction and oxidative stress in the pathogenesis of MTX-induced renal injury. Rats received MTX (a single dose of 20 or 30 mg/kg, i.p). Five days after MTX administration, serum biomarkers of kidney injury and tissue markers of oxidative stress were assessed. Moreover, kidney mitochondria were isolated, and several mitochondrial indices were determined. MTX-treated animals developed biochemical evidence of renal injury as judged by elevated serum blood urea nitrogen (BUN), creatinine (Cr) and along with hypokalemia, hypophosphatemia, hypocalcemia, and a decrease in serum glucose, and uric acid. Moreover, MTX caused an increase in kidney reactive oxygen species and lipid peroxidation. Renal glutathione reservoirs were also depleted, and tissue antioxidant capacity was decreased in MTX-treated animals. Kidney histopathological changes including interstitial inflammation, renal tubular degeneration, retraction glomeruli, and vascular congestion were also evident in MTX-treated rats. On the other hand, it was found that mitochondrial parameters including mitochondrial membrane potential, mitochondrial dehydrogenases activity, and mitochondrial glutathione and ATP content were decreased, while lipid peroxidation and mitochondrial permeabilization were increased with MTX treatment. These data suggest a role for mitochondrial dysfunction and oxidative stress in the mechanism of MTX nephrotoxicity.

Factors associated with absent microhematuria in symptomatic urinary stone patients

IntroductionThe aim of this study was to identify factors associated with absent hematuria in patients with symptomatic urinary stones. MethodsThis retrospective study analyzed the clinical and imaging findings of emergency department patients who underwent computed tomography (CT) for suspected ureteral colic over the past 2years. All patients also underwent a microscopic urinalysis, and the presence of 4 or more red blood cells/high-power field was defined as microhematuria. ResultsA total of 798 patients were included in this study. Of these patients, 750 (94.0%) presented with hematuria, while 48 (6.0%) urine samples did not have evidence of hematuria. The group with an absence of hematuria was more likely to have a lower stone location (located in an area from the distal ureter to the bladder) and perinephric stranding on CT than the hematuria group (75.0% vs. 54.3%, p=0.005; 47.9% vs. 30.5%, p=0.012, respectively). The degree of hematuria at each stone location was significantly different (p=0.001). In multivariate analysis, perinephric stranding (odds ratios (OR) 1.87 [95% confidence interval (CI) 1.01–3.46], p=0.047), a lower stone location (OR 2.72 [95% CI 1.37–5.36], p=0.004), and elevated serum blood urea nitrogen (BUN) levels (OR 1.06 [95% CI 1.01–1.12], p=0.026) were associated with absent hematuria. ConclusionsIn this large cohort of patients with renal colic, 6% had no microhematuria. Although some CT findings and elevated BUN were independently associated with hematuria absence, there was no difference in the demographics, time of presentation and degree and location of pain between the groups.

Acute Renal Failure after Cesarean Section

Urinary ascites is a rare diagnosis, commonly associated with bladder rupture. We present a case of intraperitoneal bladder injury following a Cesarean section with subsequent development of urinary ascites. Initial laboratory data with elevated serum creatinine and blood urea nitrogen (BUN) raised the suspicion for acute kidney injury due to the recent obstetrical procedure. This case highlights the importance of including intraperitoneal bladder injury with urinary ascites as a key differential in the workup of acute renal failure, particularly in the obstetric surgical setting. The rapid development of ascites with elevated serum BUN and creatinine should prompt work up for evaluating intraperitoneal bladder injury. Early diagnosis and treatment can yield gratifying results and avoid unnecessary workup of other causes of renal failure.

Dialysis Reduces Portal Pressure in Patients With Chronic Hepatitis C

The purpose of this study was to characterize changes in hepatic venous pressures in patients with chronic hepatitis C. The histology and laboratory data from patients with chronic hepatitis C who underwent a transjugular liver biopsy (TJLB) and hepatic venous pressure gradient measurement were analyzed. Portal hypertension was defined as hepatic venous pressure gradient > or =6 mm Hg. A single pathologist masked to hepatic venous pressure gradient scored liver sections for inflammation and fibrosis. The patients with high-grade inflammation (relative risk [RR] 2.82, P = 0.027, multivariate analysis) and late-stage fibrosis (RR 2.81, P = 0.022) were more likely to have a hepatic venous pressure gradient > or =6 mm Hg, while the patients on dialysis (RR 0.32, P = 0.01) were less likely to have a hepatic venous pressure gradient > or =6 mm Hg. The patients on dialysis (n = 58) had an elevated serum blood urea nitrogen and creatinine when compared with those who were not (n = 75) (47.6 +/- 3.3 and 7.98 +/- 0.4 vs. 25.9 +/- 2.0 and 1.66 +/- 0.22 mg/dL, respectively; P < 0.001). While the hepatic venous pressure gradient increased with the rising levels of liver fibrosis in the latter group (P < 0.01), it did not change in the patients on dialysis (P = 0.41). The median hepatic venous pressure gradient was especially low in late-stage fibrosis patients on dialysis when compared with the latter group (5 vs. 10 mm Hg, P = 0.017). In patients on dialysis, serum transaminases were low across all levels of fibrosis. Twenty-three of the 92 patients with early fibrosis had a hepatic venous pressure gradient > or =6 mm Hg. In patients with chronic hepatitis C, concomitant TJLB and hepatic venous pressure gradient measurement identify those who have early fibrosis and portal hypertension. Long-term hemodialysis may reduce portal pressure in these patients.

Evaluation of Subchronic Toxicity of Pet Food Contaminated with Melamine and Cyanuric Acid in Rats

Outbreaks of food-associated renal failure in pets occurred in Asia and the United States of America in 2004 and 2007. They were related to the combined intoxication of cyanuric acid and melamine. Our aims were to investigate cyanuric acid and melamine contamination of pet food and to examine subchronic toxicity in rats. Levels of 10%, 20%, 50%, and 50%-100% (w/w) of contaminated pet food were fed to rats for three months. Analytical results revealed that the tainted food contained significant levels of cyanuric acid and melamine in a ratio of 1:6.8. Rats fed the diet of 50%-100% for three months exhibited elevated serum blood urea nitrogen and creatinine, as well as dose-dependent melamine/cyanuric acid crystal-induced nephrotoxicity. The melamine/cyanuric acid crystals of various sizes were mixed with necrotic cell debris and inflammatory cells, accompanied by tubular dilation and interstitial fibrosis. The immunohistochemistry index of proliferative cellular nuclear antigen and osteopontin in the kidney of the 50%-100% group were elevated, indicating regeneration of renal cells and the formation of crystals. In conclusion, the combination ratio of cyanuric acid to melamine and the acidic urine content were two factors that, upon repeated exposure, determined the severity of the nephrotoxicity.

Cannabidiol Attenuates Cisplatin-Induced Nephrotoxicity by Decreasing Oxidative/Nitrosative Stress, Inflammation, and Cell Death

The platinum compound cisplatin is one of the most potent chemotherapy agents available to treat various malignancies. Nephrotoxicity is a common complication of cisplatin chemotherapy, which involves increased oxidative and nitrosative stress, limiting its clinical use. In this study, we have investigated the effects of a nonpsychoactive cannabinoid cannabidiol, which was reported to exert antioxidant effects and has recently been approved for the treatment of inflammation, pain, and spasticity associated with multiple sclerosis in patients in a mouse model of cisplatin-induced nephropathy. Cisplatin induced increased expression of superoxide-generating enzymes RENOX (NOX4) and NOX1, enhanced reactive oxygen species generation, inducible nitric-oxide synthase expression, nitrotyrosine formation, apoptosis (caspase-3/7 activity, DNA fragmentation, and terminal deoxynucleotidyl transferase dUTP nick-end labeling staining), poly(ADP-ribose) polymerase activity, and inflammation (tumor necrosis factor-alpha and interleukin-1beta) in the kidneys of mice, associated with marked histopathological damage and impaired renal function (elevated serum blood urea nitrogen and creatinine levels) 72 h after the administration of the drug. Treatment of mice with cannabidiol markedly attenuated the cisplatin-induced oxidative/nitrosative stress, inflammation, and cell death in the kidney, and it improved renal function. Thus, our results suggest that cannabidiol may represent a promising new protective strategy against cisplatin-induced nephrotoxicity.

Protective Effect of a Pancreatic Elastase Inhibitor Against a Variety of Acute Pancreatitis in Rats

Protective effect of trifluoroacetyl-L-lysyl-L-alaninanilide hydrochloride (compound 1), a pancreatic elastase inhibitor, on three types of acute pancreatitis models was examined in rats. Mild, moderate and severe acute pancreatitis were induced by cerulein, the closed duodenal loop method and retrograde injection of a taurocholate plus trypsin solution into the pancreatic duct, respectively. Intravenous infusion of compound 1 at a dose of 30 mg/kg/hr resulted in lower increases in serum amylase, lipase, blood urea nitrogen (BUN) and creatinine levels in rats with mild cerulein-induced edematous pancreatitis. Compound 1 had no beneficial effect on pancreatitis in rats with moderate pancreatitis. In rats with severe pancreatitis, prophylactic treatment of compound 1 (30 mg/kg/hr) reduced both elevated serum BUN level and ascitic volume, and it histologically inhibited the extent of pancreatic edema and hemorrhage. These results suggest that pancreatic elastase is partially responsible for pancreatic edema and hemorrhage exhibited by rats with severe acute pancreatitis.

Improved survival from fungaemia in patients with haematological malignancies: Analysis of risk factors for death and usefulness of early antifungal therapy

Fourty-three episodes of fungaemia encountered from 1978 to 1991 in 43 patients with haematological malignancies are reviewed here to analyse the risk factors for death and to evaluate the efficacy of early antifungal therapy. Low serum cholinesterase and elevated serum blood urea nitrogen were significantly associated with fungaemic death, defined as death occurring within 2 weeks after documentation of fungaemia. Overall death rate from fungaemia was 62.8%. Before the introduction of early antifungal therapy in 1986, however, fungaemic mortality was 85.7%; it was reduced to 51.7% thereafter (p = 0.01). Determination of plasma (1-->3)-beta-D-glucan was helpful in detecting deep fungal infections and initiating antifungal therapy early.

Toxicologic changes in rats fed graded dietary levels of ochratoxin A

In a short-term study, groups of weanling male rats were fed a semipurified diet containing 0, 2.4, 4.8, 9.6 or 24 ppm of ochratoxin A for a period of 2 weeks. Growth retardation and reduced food consumption were observed in rats fed 9.6 or 24 ppm but not in those fed 2.4 or 4.8 ppm of the compound. Rats fed 24 ppm of ochratoxin A had elevated serum blood urea nitrogen (BUN) values and significantly increased kidney weights accompanied by marked degenerative changes involving the entire tubular system. Similar, but less extensive, changes were noted in the 4.8 and 9.6 ppm groups. In a subacute study groups of 15 weanling male and female rats were fed a semipurified diet for 90 days containing 0, 0.2, 1.0 or 5.0 ppm of ochratoxin A. Body weight was significantly reduced in the 5.0 ppm group. In contrast to the short-term study, relative kidney weights were reduced in the 1.0 and 5.0 ppm groups, and the latter group had elevated BUN values. Dose-related pathologic changes were noted in the kidneys of all treated rats. In the 0.2 ppm group a few scattered cells in the proximal convoluted tubules underwent granular eosinophilic degeneration, and a few cells developed bizarre giant nuclei. At the higher doses, similar, but more extensive changes were observed.