Urinary cancer detection by the target urine volatile organic compounds biosensor platform.

Volatile organic compounds (VOCs) have grown due to their crucial role in transitioning from invasive to noninvasive cancer diagnostic methods. This study aimed to assess the feasibility of the metal oxide biosensor platform using urine VOCs for detecting genitourinary cancers. Five different commercially available semiconductor sensors were chosen to detect specific VOCs (methane, iso-butane, hydrogen, ethanol, hydrogen sulfide, ammonia, toluene, butane, propane, trimethylamine, and methyl-mercaptan). Changes in electrical resistance due to temperature variations from the voltage heater were examined to characterize VOC metabolism. Logistic regression and ROC analysis were employed to evaluate potential urine VOCs for genitourinary cancer determination. This study involved 64 participants which were categorized into a cancer and a non-cancer group. The genitourinary cancer (confirmed by tissue pathology) comprised 32 patients, including renal cell carcinoma (3.1%), transitional cell carcinoma (46.9%), and prostate cancer (50%). The non-cancer comprised 32 patients, with 9 healthy subjects and 23 individuals with other genitourinary diseases. Results indicated that VOC sensors for methane, iso-butane, hydrogen, and ethanol, at a voltage heater of 2000 mV, demonstrated a significant predictive capability for genitourinary cancer with P = 0.013. The ROC of these biomarkers also indicated statistical significance in predicting the occurrence of the disease (P < 0.05). This report suggested that methane, iso-butane, hydrogen, and ethanol VOCs exhibited potential for diagnosing genitourinary cancer. Developing gas metal oxide sensors tailored to these compounds, and monitoring changes in electrical resistance, could serve as an innovative tool for identifying this specific type of cancer.

Manifestation of rs1888747 polymorphisms in the FRMD3 gene in diabetic kidney disease and diabetic retinopathy in type 2 diabetes patients.

BACKGROUND: FRMD3 polymorphisms has suggested that they could be an alternative test to differentiate diabetic nephropathy (DN) from nondiabetic renal disease (NDRD) in type 2 diabetes mellitus (DM) patients. This study was performed to investigate the relationship between the FRMD3 gene and clinical characteristics of DN. METHODS: Patients who already had renal pathologic results were tested for FRMD3 polymorphisms. The subjects were classified into three groups; DN with diabetic retinopathy (DR), DN without DR, and DM with NDRD. FRMD3 polymorphisms were analyzed in each group. RESULTS: The prevalence of GG, CG, and CC was 44.4%, 42.2%, and 13.3% respectively. There was no significant difference in clinical parameters, which consisted of disease duration, proteinuria, and complications in DN with or without DR and DM with NDRD. The G allele was mainly found in DN with DR patients (50.8%) whereas the C allele was found in DM with NDRD patients (43.5%) (p = 0.02). There was a significant association between the CC genotype in NDRD when compared to GG (p = 0.001). In addition, the C allele was 2.10-fold more often associated with NDRD than the G allele (p = 0.03). The CC genotype was correlated with risk for NDRD than the GG and GC genotypes, with odds ratios of 6.89 and 4.91, respectively (p = 0.02). CONCLUSION: C allele presentation, especially homozygous CC, was associated with NDRD pathology in patients with overt proteinuria. Hence, kidney biopsy is suggested in those with the C allele or homozygous CC genotype, regardless of retinopathy manifestations.

The Association Between GFR Evaluated by Serum Cystatin C and Proteinuria During Pregnancy.

INTRODUCTION: Physiological changes in pregnancy result in increased cardiac output and renal blood flow, with a consequential increase in proteinuria. Data from studies of the relationship between proteinuria caused by isolated proteinuria and glomerular filtration rate (GFR) are still limited. The objective of this study was to investigate the effects of isolated proteinuria on the cystatin C-based GFR in the third trimester of pregnancy. METHODS: Data were collected from pregnant women in their third trimester whose serum creatinine levels were normal. The GFR of each participant was measured using serum cystatin C levels, and proteinuria was measured using urine protein-creatinine ratios. The participants were divided into 3 groups according to their level of proteinuria: normal (<150 mg/d), physiological (150-300 mg/d), and gestational (>300 mg/d). Changes in GFR were recorded for each group. RESULTS: The study included 89 participants, of whom 66.3% had levels of proteinuria that did not differ from that of the normal population (<150 mg/d). The incidence of physiological and gestational proteinuria was 21.4% and 12.4%, respectively. The results demonstrate that proteinuria >101.50 mg/d was significantly associated with declined estimated glomerular filtration rate (eGFR) (r = -0.34, P = 0.01). The analysis found that proteinuria >491.27 mg/d led to a risk of GFR <90 ml/min with an odds ratio of 12.69, P = 0.02 when adjusted for systolic blood pressure (SBP), diastolic blood pressure (DBP), and body mass index. CONCLUSION: This study suggests that the term "physiological proteinuria" is a misnomer. When used in the traditional manner, creatinine level has inadequate sensitivity to estimate GFR in pregnant women. We found that there is a significant decline in GFR when urine protein > 101.5 mg/d, which could be an early biomarker for renal pathology rather than pregnancy physiology, suggesting that further workup and precaution is required.

Assessment of preeclampsia risk by use of serum ionized magnesium-based equation.

BACKGROUND: Preeclampsia is a common medical complication in pregnancy. It has been reported to be associated with decreased serum magnesium levels. However, there has not been evidence demonstrating utilization of change in magnesium for prediction of preeclampsia. The purpose of this study was to develop magnesium fraction-based equations which took other significant clinical risk factors into consideration for prediction of preeclampsia. METHODS: We collected serum total and ionized magnesium ionized magnesium levels from 84 pregnant women diagnosed with preeclampsia after week 20 of pregnancy. The ionized magnesium fraction was then calculated by the percentage ratio of ionized and total magnesium level. RESULTS: Sixty-four (76.19%) women had normal pregnancy and 20 (23.81%) developed preeclampsia. The ionized magnesium fraction was significantly lower in preeclampsia group (23.95 ± 4.7% vs. 26.28 ± 2.3%, p = .04). Additionally, lower ionized magnesium fraction (24.67%), teenage and elderly primigravida were significantly associated with preeclampsia (OR = 4.41, 95% CI: 1.46-13.40, OR = 5.47, 95% CI: 1.85-35.42 and OR = 11.11, 95% CI: 1.09-113.78, respectively). Consequently, we attempted to develop ionized magnesium fraction-based equations calculate risk scores for preeclampsia. The area of ROC for predictive accuracy of the model was 0.77 (p < .001) and ROC suggested that the score of 0.27 would be a threshold for screening preeclampsia with 70% sensitivity and 81% specificity. CONCLUSIONS: Ionized magnesium fraction may have been appropriate for screening of preeclampsia. We suggested blood testing on total and ionized magnesium concentrations as well as calculation of ionized magnesium fraction in addition to routine antenatal care for better screening of the disease.

Effect of Magnesium on Glomerular Filtration Rate and Recovery of Hypertension in Women with Severe Preeclampsia.

INTRODUCTION: Magnesium sulfate is used for preventing seizures in patients with severe preeclampsia. Previous studies have demonstrated that magnesium plays a significant role in the endothelial function and might have clinically beneficial vasodilating properties. OBJECTIVES: This study is aimed at evaluating the effect of magnesium sulfate on the glomerular filtration rate (GFR) during the first 24 h after delivery and during the duration of recovery from hypertension in preeclampsia. METHODS: Severe preeclamptic patients who had normal serum creatinine levels (0.4-0.8 mg/dL) were included in the study. Twenty-three women with severe preeclampsia were divided into groups of 9, 8, and 6, and given 1.0, 1.5, and 2.0 g/h of magnesium sulfate, respectively. Magnesium sulfate infusion was used as seizure prophylaxis for 24 h after delivery. The cystatin C-based GFR was monitored for 24 h, and the blood pressure was recorded for 12 weeks postpartum. RESULTS: Despite the minimal improvement of GFR 24-h after treatment initiation, survival analysis demonstrated a statistically significant relationship (log rank, p = 0.04) between magnesium dosage and recovery period from hypertension. The group receiving 2.0 g/h of magnesium experienced the shortest recovery period from hypertension (6.5 ± 1.8 days). Meanwhile, the other groups required 66.0 ± 26.9 and 48.3 ± 15.6 days to recover after 1.0 and 1.5 g/h of magnesium infusion, respectively. CONCLUSION: Magnesium sulfate has no impact on GFR improvement during the first 24 h after delivery. However, magnesium maintenance infusion at 2.0 g/h is capable of preventing seizure by optimizing the therapeutic magnesium level (4.8-8.4 mg/dL) and shortening the hypertensive episode in preeclampsia.

Cystatin C as a novel predictor of preterm labor in severe preeclampsia.

BACKGROUND: The most common cause of acute kidney injury (AKI) in pregnancy is preeclampsia. Serum cystatin C (CysC) is a potential biomarker of early kidney damage as its levels are not disturbed by volume status changes in pregnancy, and serum CysC levels could serve as a replacement for conventionally used creatinine. In this study, we investigated the serum levels of CysC in severe preeclampsia cases and the associations between CysC levels and poor obstetric outcomes. METHODS: Our cohort included severe preeclampsia patients with a normal serum creatinine level. Creatinine was measured to calculate estimated glomerular filtration rate (eGFR) based on the Cockcroft and Gault, Modification of Diet in Renal Disease Study (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations, while CysC was measured to calculated eGFR based on a CysC-based equation. We then evaluated the correlations between serum CysC level, eGFR, and obstetric outcomes. RESULTS: Twenty-six patients were evaluated of which 38.5% delivered preterm and 30.8% had low-birth weight babies. Unlike creatinine-based eGFR and CysC-based eGFR, serum CysC demonstrate significant negative correlation with gestational age. Receiver operating characteristic curve analysis indicated that serum CysC is a potential biomarker of preterm delivery with a cut-off serum level of 1.48 mg/L with 80% sensitivity and 75% specificity. CONCLUSION: GFR estimation using CysC is likely to be inaccurate in pregnancy. However, we found a significant correlation between preterm delivery and serum CysC level. Our results suggest that serum CysC level has the potential to predict preterm delivery in severe preeclampsia patients.

Measurement accuracy of total cell volume by automated dialyzer reprocessing: A prospective cohort study.

INTRODUCTION: Dialyzer reprocessing machines have replaced human labor in preparing re-usable dialyzers. It also made the process of total cell volume (TCV) measurement become faster. Nevertheless, there has been a lack of data on efficacy of weight evaluation on TCV by machine compared to volume evaluation by the conventional method. The aim of this study was to evaluate the efficacy of TCV measurement performed by Kidney-Kleen® reprocessing machine, produced by MEDITOP Company in Thailand, compared to that of the conventional method. METHODS: This prospective cohort study was performed during September 2014 to December 2015.The low-flux (N = 101) and high-flux dialyzers (N = 100) were included for TCV evaluation. Reused times were up to 5 in the low-flux and 20 in the high-flux dialyzers. The Bland Altman analysis was used to evaluate value measured by different methods. RESULTS: The values measured by weight evaluation (by machine) were higher than those obtained by volumetric evaluation of the conventional method in the low-flux (0.81 ± 0.20%) and high-flux (1.32 ± 0.39%) dialyzers. The correlation of TCV values of the two methods were r = 0.98, p < 0.001 and r = 0.71, p < 0.001 for the low- and high-flux dialyzers. Moreover, there was robust association and agreement between the two methods, confirmed by the Bland-Altman Analysis, which suggested that the values acquired by machine were within the limits of agreement, indicating acceptable accuracy of equipment. CONCLUSION: The approach of measurement differed from that of the conventional method (weight evaluation was used instead of volumetric evaluation), the reprocessing machine could offer accurate results.

Molecular phenotypes of acute kidney injury in kidney transplants.

Little is known regarding the molecular phenotype of kidneys with AKI because biopsies are performed infrequently. However, all kidney transplants experience acute injury, making early kidney transplants an excellent model of acute injury, provided the absence of rejection, because donor kidneys should not have CKD, post-transplant biopsies occur relatively frequently, and follow-up is excellent typically. Here, we used histopathology and microarrays to compare indication biopsies from 26 transplants with acute injury with 11 pristine protocol biopsies of stable transplants. Kidneys with acute injury showed increased expression of 394 transcripts associated with the repair response to injury, including many epithelium-like injury molecules tissue, remodeling molecules, and inflammation molecules. Many other genes also predicted the phenotype, including the acute injury biomarkers HAVCR1 and IL18. Pathway analysis of the injury-repair transcripts revealed similarities to cancer, development, and cell movement. The injury-repair transcript score in kidneys with acute injury correlated with reduced graft function, future renal recovery, brain death, and need for dialysis, but not with future graft loss. In contrast, histologic features of acute tubular injury did not correlate with function or with the molecular changes. Thus, the transcripts associated with repair of injury suggest a massive coordinated response of the kidney parenchyma to acute injury, providing both an objective measure for assessing the severity of injury in kidney biopsies and validation for many biomarkers of AKI.

Urine potassium per hour as a marker for renal potassium losses.

BACKGROUND: Hypokalemia, serum potassium (K) < 3.5 mEq/L, is a serious and common clinical problem. The traditional diagnosis of renal potassium losses is 24-hr urine potassium (24U(K)) > or = 20 mEq/day during hypokalemia. Immediate replacement of potassium is often required to prevent complication but may normalize serum K during 24-hr urine collection and render the test inconclusive. MATERIAL AND METHOD: The authors examined the ability of urinary indices including 24U(K), transtubular potassium gradient (TTKG), fractional excretion of potassium (FE(K)), urine potassium-creatinine ratio (U(K/Cr)) and spot U(K) and introduced urine potassium per hour during the first 8 hours (U(K)/hr) as a novel index for evaluation of hypokalemia during treatment. Any serum K level > or = 4 mEq/L during urine collection was defined as normalized serum K. In the present study, the final classification of renal K losses in non-normalized 24-hr serum K group was made when 24U(K) > or = 20 mEq/day. In normalized group, the final classification of renal or non-renal K losses was based on the majority of the results of four urine indices including TTKG, FE(K) U(K/Cr) and spot U(K). RESULTS: Of 61 patients (renal:non-renal = 50:11), 51% and 18% met the criteria of normalized 24-hr and 8-hr serum K. Over all, the U(K)/hr > or = 0.9 mEq/hr can indicate renal K losses with a sensitivity of 96% and specificity of 72.7% compared with the 24U(K) > or = 20 mEq/day of 100% and 54.5%, respectively. In a subgroup of normalized 24-hr serum K, the sensitivity and specificity of U(K)/hr = 95.5% and 77.8% whereas 24U(K) = 100% and 44.4%, respectively CONCLUSION: U(K)/hr is a new practical, simple, and reliable marker that can be applied to evaluate hypokalemic patients during treatment with comparable sensitivity and specificity with 24U(K).

Pulmonary hemorrhage with acute renal injury in a patient with IgA nephropathy.

IgA nephropathy (IgAN) is a form of glomerular diseases which is usually aggravated by infection in respiratory or gastrointestinal systems. The clinical manifestations in IgAN can be asymptomatic microscopic hematuria, gross hematuria, nephritic syndrome, nephrotic syndrome or acute renal injury from crescentic glomerulonephritis. Acute interstitial nephritis (AIN) has been previously described as an unusual cause of acute renal injury in IgAN. Hemoptysis from diffuse pulmonary hemorrhage is a rare manifestation in IgAN. We reported a patient who presented with fever hemoptysis from diffuse pulmonary hemorrhage, and acute renal injury. Renal biopsy revealed IgAN concomitant with AIN which was the cause of renal dysfunction. We conclude that pulmonary hemorrhage and acute interstitial nephritis can be found in IgAN. The etiology of pulmonary hemorrhage and acute interstitial nephritis might be from infection. Renal biopsy is a mandatory investigation to make the correct diagnosis.