Sole measurement of plasma vitamin B12 is no longer enough to identify vitamin B12 (B12) deficiency. When plasma vitamin B12 is in the low-normal range, especially between 201 and 350 ng/L, B12 deficiency should be assessed by measurements of plasma homocysteine and/or plasma methylmalonic acid (MMA). However, these biomarkers also accumulate during renal impairment, leading to a decreased specificity for B12 deficiency. In such cases, urinary methylmalonic acid/creatinine ratio (uMMA/C) could be of interest, due to the stable urinary excretion of MMA. The objectives were to evaluate the influence of renal impairment on uMMA/C compared to plasma homocysteine and plasma methylmalonic acid, and to determine the diagnostic performances of uMMA/C in the diagnosis of B12 deficiency. We prospectively studied 127 patients with a plasma B12 between 201 and 350 ng/L. We noticed that uMMA/C was not dependent on renal function (p = 0.34), contrary to plasma homocysteine and plasma methylmalonic acid. uMMA/C showed a perspective diagnostic performance (AUC 0.71 [95% CI: 0.62-0.80]) and the threshold of 1.45 umol/mmol presented a high degree of specificity (87.9% [95% CI: 72.0-98.9]). In conclusion, uMMA/C is a promising biomarker to assess vitamin B12 status in doubtful cases, notably during renal impairment.

Graft failure (GF) remains a significant limitation to improve long-term outcomes in renal transplant recipients (RTR). Urinary epidermal growth factor (uEGF) is involved in kidney tissue integrity, with a reduction of its urinary excretion being associated with fibrotic processes and a wide range of renal pathologies. We aimed to investigate whether, in RTR, uEGF is prospectively associated with GF. In this prospective cohort study, RTR with a functioning allograft ≥1-year were recruited and followed-up for three years. uEGF was measured in 24-hours urine samples and normalized by urinary creatinine (Cr). Its association with risk of GF was assessed by Cox-regression analyses and its predictive ability by C-statistic. In 706 patients, uEGF/Cr at enrollment was 6.43 [IQR 4.07-10.77] ng/mg. During follow-up, 41(6%) RTR developed GF. uEGF/Cr was inversely associated with the risk of GF (HR 0.68 [95% CI 0.59-0.78]; P < 0.001), which remained significant after adjustment for immunosuppressive therapy, estimated Glomerular Filtration Rate, and proteinuria. C-statistic of uEGF/Cr for GF was 0.81 (P < 0.001). We concluded that uEGF/Cr is independently and inversely associated with the risk of GF and depicts strong prediction ability for this outcome. Further studies seem warranted to elucidate whether uEGF might be a promising marker for use in clinical practice.

Renal function declines after partial nephrectomy due to ischemic reperfusion injury induced by surgical insult or renal artery clamping. The effect of remote ischemic preconditioning (RIPC) on reducing renal injury after partial nephrectomy has not been studied regarding urinary biomarkers. Eighty-one patients undergoing partial nephrectomy were randomly assigned to either RIPC or the control group. RIPC protocol consisted of four cycles of five-min inflation and deflation of a blood pressure cuff to 250 mmHg. Serum creatinine levels were compared at the following time points: preoperative baseline, immediate postoperative, on the first and third days after surgery, and two weeks after surgery. The incidence of acute kidney injury, other surgical complication rates, and urinary biomarkers, including urine creatinine, β-2 microglobulin, microalbumin, and N-acetyl-beta-D-glucosaminidase were compared. Split renal functions measured by renal scan were compared up to 18 months after surgery. There was no significant difference in the serum creatinine level on the first postoperative day (median (interquartile range) 0.87 mg/dL (0.72-1.03) in the RIPC group vs. 0.92 mg/dL (0.71-1.12) in the control group, p = 0.728), nor at any other time point. There was no significant difference in the incidence of acute kidney injury. Secondary outcomes, including urinary biomarkers, were not significantly different between the groups. RIPC showed no significant effect on the postoperative serum creatinine level of the first postoperative day. We could not reveal any significant difference in the urinary biomarkers and clinical outcomes. However, further larger randomized trials are required, because our study was not sufficiently powered for the secondary outcomes.

Both serum creatinine (sCr) and estimated glomerular filtration rate (eGFR) have been used to assess kidney function in public health check-ups. However, when the sCr is within the normal levels but the eGFR is <60 mL/min/1.73 m², a dilemma arises, as the patients might progress to chronic kidney disease (CKD) after several years. We aimed to evaluate the association between normal sCr and the risk of incident CKD in the general population. For this, 9445 subjects from the Korean Genome and Epidemiology Study, with normal sCr and eGFR of >60 mL/min/1.73 m² were analyzed. The subjects were classified into quartiles based on sCr levels. The primary outcome was the development of eGFR <60 mL/min/1.73 m² on two consecutive measures. During a mean follow-up of 8.4 ± 4.3 years, 779 (8.2%) subjects developed eGFR <60 mL/min/1.73 m². The incidence of the development of eGFR <60 mL/min/1.73 m² was higher in the higher quartiles than in the lowest quartile. In multivariable Cox analysis, the highest quartile was associated with an increased risk for the development of eGFR <60 mL/min/1.73 m² (hazard ratio (HR), 4.71; 95% confidence interval (CI), 3.29⁻6.74 in females; HR, 12.77; 95% CI, 7.69⁻21.23 in males). In the receiver operating characteristic curve analysis, adding sCr to the traditional risk factors for CKD improved the accuracy of predicting the development of eGFR <60 mL/min/1.73 m² (area under the curve, 0.83 vs. 0.80 in females and 0.85 vs. 0.78 in males), and the cutoff value of sCr was 0.75 mg/dL and 0.78 mg/dL in females and males. Cautious interpretation is necessary when sCr is within the normal range, considering that the upper normal range of sCr has a higher risk of CKD development.

Acute kidney injury (AKI) is one of the most common complications in critically ill patients. In recent years, studies have focused on exploring new biomarkers for the early diagnosis and prognosis of AKI. The aim of this study was to investigate serum prognostic biomarkers (neutrophil gelatinase-associated lipocalin, NGAL, and creatinine) of AKI in critically ill patients. The study included 266 critically ill, initially nonseptic, patients admitted to a multidisciplinary ICU. Serum levels of NGAL and creatinine were measured at ICU admission. ROC curves were generated to estimate the prognostic value of the biomarkers, while a logistic regression analysis was performed to assess their association with an increased AKI risk. Patients were divided in two groups based on the development (n = 98) or not (n = 168) of AKI during their ICU stay. Serum NGAL levels at ICU admission were significantly higher in those who subsequently developed AKI compared to those who did not (p < 0.0001). NGAL was shown to be more accurate in predicting AKI development than creatinine; furthermore, NGAL levels were associated with an increased risk of AKI development (1.005 (1.002-1.008), p < 0.0001). In the present study, we were able to demonstrate that increased serum NGAL levels at ICU admission might be predictive of AKI development during ICU hospitalization. Further studies are needed to support NGAL as a prognostic marker of acute kidney injury.

Changes in kidney function in extremely preterm infants (EPT) with conservatively managed hemodynamically significant (HS) patent ductus arteriosus (PDA) are not known well. We aimed to present the postnatal course in serum creatinine levels (sCr), prevalence of acute kidney injury (AKI), then relevance between AKI and adverse outcomes in EPT with conservatively managed HS PDA. By review of medical records, we analyzed the postnatal course of sCr and prevalence of stage 3 AKI defined by the modified Kidney Disease Improving Global Outcome (KDIGO) in EPT at gestational age of 23 to 26 weeks with conservatively treated HS PDA. We investigated if the presence and/or prolonged duration of stage 3 AKI elevated the risk of adverse outcomes. The results showed that, neither factor was associated with adverse outcomes. While the average PDA closure date was at postnatal day (P) 41 and 53, sCr peaked at P 10 and 14 and the cumulative prevalence of stage 3 AKI was 57% and 72% in the EPT of 25-26 and 23-24 weeks' gestation, respectively. The high prevalence of stage 3 AKI without adverse outcomes in EPT with conservatively managed HS PDA suggests that it might reflect renal immaturity rather than pathologic conditions.

Cardiac troponins are crucial for the diagnosis of acute myocardial infarction. Despite known differences in their diagnostic implication, there are no recommendations for only one of the two troponins, cardiac troponin I (cTnI) and troponin T (cTnT) so far. In an everyday routine diagnostic, cTnT (Roche) as well as cTnI (Abbott) were measured in 5667 samples from 3264 patient cases. We investigated the number of identical or discrepant troponin findings. Regarding cTnI, we considered both, sex-dependent and unisex cutoffs. In particular, the number of cTnT positive and cTnI negative results was strikingly high in 14.0% of cTnT positive samples and increases to 23.8% by using sex-specific cTnI cutoffs. This group was considerably greater than the group of cTnI positive and cTnT negative results, also after elimination of patients with an eGFR < 60 mL/min/1.73 m2. Comparing the troponin cases with a dynamic increase or decrease between two measurements, we saw a balanced number of discrepant cases (between cTnT+/cTnI- and cTnT-/cTnI+), which was, however, still present. Using ROC analysis, sex-dependent cutoffs improved sensitivity and specificity of cTnI. This study shows in a large cohort that comparing the two cardiac troponins does not amount to identical analytical results. Consideration of sex-dependent cutoffs may improve sensitivity and specificity.

This observational, cross-sectional, epidemiological analysis investigated relationships of kidney function to urine calcium and other variables. The analyses targeted two population-based samples of adults (Gubbio study and Moli-sani study: n = 3508 and 955, respectively). Kidney function was assessed as estimated glomerular filtration rate (eGFR). Calcium/creatinine ratio (Ca/Cr) was used as index of urinary calcium in timed overnight urine under fed condition (Gubbio study), morning urine after overnight fast (Gubbio study), and first-void morning urine (Moli-sani study). Moli-sani study included also data for glomerular filtered calcium load, tubular calcium handling, and serum phosphorus, parathyroid hormone, 1,25-dihydroxyvitamin D, calcium, and 25-hydroxyvitamin D. eGFR positively and independently related to Ca/Cr (p < 0.001). In multivariate analyses, eGFR lower by 10 mL/min × 1.73 m2 related to overnight urine Ca/Cr lower by 14.0 mg/g in men and 17.8 mg/g in women, to morning urine Ca/Cr lower by 9.3 mg/g in men and 11.2 mg/g in women, and to first-void urine Ca/Cr lower by 7.7 mg/g in men and 9.6 mg/g in women (p < 0.001). eGFR independently related to glomerular filtered calcium load (p < 0.001) and did not relate to tubular calcium handling (p ≥ 0.35). In reduced eGFR only (<90 mL/min × 1.73 m2), low urine Ca/Cr independently related to low serum 1,25-dihydroxyvitamin D (p = 0.002) and did not relate to hyperphosphatemia, high serum parathyroid hormone, or hypocalcemia (p ≥ 0.14). Population-based data indicated consistent associations of lower kidney function with lower urine calcium due to reduction in glomerular filtered calcium. In reduced kidney function, relative hypocalciuria associated with higher prevalence of low serum 1,25-dihydroxyvitamin D.

Longitudinal changes of renal function help inform patients' clinical courses and improve risk stratification. Rare studies address risk factors predicting changes in estimated glomerular filtration rate (eGFR) over time in older adults, particularly of Chinese ethnicity. We identified prospectively enrolled community-dwelling older adults (≥65 years) receiving annual health examinations between 2005 and 2015 with serum creatinine available continuously in a single institute, and used linear regression to derive individual's annual eGFR changes, followed by multivariate logistic regression analyses to identify features associated with different eGFR change patterns. Among 500 elderly (71.3 ± 4.2 years), their mean annual eGFR changes were 0.84 ± 1.67 mL/min/1.73 m²/year, with 136 (27.2%) and 238 (47.6%) classified as having downward (annual eGFR change <0 mL/min/1.73 m²/year) and upward eGFR (≥1 mL/min/1.73 m²/year) trajectories, respectively. Multivariate logistic regression showed that higher age (odds ratio (OR) 1.08), worse renal function (OR 13.2), and more severe proteinuria (OR 9.86) or hematuria (OR 3.39) were predictive of a declining eGFR while greater waist circumference (OR 1.06) and higher leukocyte counts (OR 1.21) were predictive of an uprising 10-year eGFR. These findings elucidate important features associated with geriatric renal function variations, which are expected to improve their renal care.

Non-steroidal anti-inflammatory drugs (NSAIDs) can be used as opioid alternatives for patient-controlled analgesia (PCA). However, their use after nephrectomy has raised concerns regarding possible nephrotoxicity. This study compared postoperative renal function and postoperative outcomes between patients using NSAID and patients using opioids for PCA in nephrectomy. In this retrospective observational study, records were reviewed for 913 patients who underwent laparoscopic or robot-assisted laparoscopic nephrectomy from 2015 to 2017. After propensity score matching, 247 patients per group were analyzed. Glomerular filtration rate (GFR) percentages (postoperative value divided by preoperative value), blood urea nitrogen (BUN)/creatinine ratios, and serum creatinine percentages were compared at 2 weeks, 6 months, and 1 year after surgery between users of NSAID and users of opioids for PCA. Additionally, postoperative complication rates, postoperative acute kidney injury (AKI) incidences, postoperative pain scores, and lengths of hospital stay were compared between groups. Postoperative GFR percentages, BUN/creatinine ratios, and serum creatinine percentages were similar between the two groups. There were no significant differences in the rates of postoperative complications, incidences of AKI, and pain scores at 30 min, 6 h, 48 h, or 7 days postoperatively. The length of hospital stay was significantly shorter in the NSAID group than in the opioid group. This study showed no association between the use of NSAID for PCA after laparoscopic nephrectomy and the incidence of postoperative renal dysfunction.

Cardiovascular risk factors, pre-existing comorbidities, molecular factors, and the direct effects of second- and third-generation BCR-ABL1 tyrosine kinase inhibitors on the vascular endothelium contribute to the progression of cardiovascular (CV) events, especially atherothrombotic conditions. The study objective was to evaluate comorbidities, the cardiovascular risk profile, and events throughout the chronic myeloid leukaemia disease course.

We sought to evaluate the association of postoperative acute kidney injury (AKI) adjusted for parenchymal mass reduction with long-term renal function in patients undergoing partial nephrectomy. A total of 629 patients undergoing partial nephrectomy were reviewed. Postoperative AKI was defined by the Kidney Disease: Improving Global Outcomes (KDIGO) serum creatinine criteria, by using either the unadjusted or adjusted baseline serum creatinine level, accounting for renal parenchymal mass reduction. Estimated glomerular filtration rates (eGFRs) were followed up to 61 months (median 28 months) after surgery. The primary outcome was the functional change ratio (FCR) of eGFR calculated by the ratio of the most recent follow-up value, at least 24 months after surgery, to eGFR at 3-12 months after surgery. Multivariable linear regression analysis was performed to evaluate whether unadjusted or adjusted AKI was an independent predictor of FCR. As a sensitivity analysis, functional recovery at 3-12 months after surgery compared to the preoperative baseline was analyzed. Median parenchymal mass reduction was 11%. Unadjusted AKI occurred in 16.5% (104/625) and adjusted AKI occurred in 8.6% (54/629). AKI using adjusted baseline creatinine was significantly associated with a long-term FCR (β = -0.129 ± 0.026, p < 0.001), while unadjusted AKI was not. Adjusted AKI was also a significant predictor of functional recovery (β = -0.243 ± 0.106, p = 0.023), while unadjusted AKI was not. AKI adjusted for the parenchymal mass reduction was significantly associated with a long-term functional decline after partial nephrectomy. A creatinine increase due to remaining parenchymal ischemic injury may be important in order to predict long-term renal functional outcomes after partial nephrectomy.

Intra-abdominal hypertension (IAH) causes severe organ dysfunction. Our aim is to evaluate the effect of increased intra-abdominal pressure (IAP) on renal function, hypothesizing that venous congestion may increase proteinuria and fluid retention without endothelial dysfunction. Three urine samples were collected from 32 non-pregnant women undergoing laparoscopic-assisted vaginal hysterectomy (LAVH) and from 10 controls placed in Trendelenburg position for 60 min. Urine sampling was done before (PRE), during or immediately after (PER), and two hours after (POST) the procedure. Urinary albumin, protein and creatinine concentrations were measured in each sample, and ratios were calculated and compared within and between groups. During LAVH, the albumin/creatinine ratio (ACR) increased and persisted POST-procedure, which was not observed in controls. A positive correlation existed between the LAVH duration and the relative change in both ACR and protein/creatinine ratio (PCR) PER- and POST-procedure. Iatrogenic IAH increases urinary ACR and PCR in non-pregnant women via a process of venous congestion. This mechanism might explain the presentation of one specific subtype of late-onset preeclampsia, where no drop of maternal cardiac output is observed.

Serum creatinine is used to measure the estimated glomerular filtration rate (eGFR); however, it is influenced by muscle mass and may therefore overestimate renal function in patients with sarcopenia. We examined calf circumference (CC) as a convenient muscle mass evaluation tool that can potentially indicate the need to test for cystatin C instead of creatinine in elderly inpatients. We retrospectively reviewed the electronic health record of 271 inpatients aged 65 or over. CC was determined by measuring the thickest part of the nondominant calf. eGFRcys and eGFRcr were calculated using cystatin C and creatinine levels, respectively. We evaluated optimum CC cutoff values using the eGFRcys/eGFRcr ratio for detecting hidden renal impairment (HRI, defined as eGFRcr ≥ 60 mL/min/1.73 m2 but eGFRcys < 60 mL/min/1.73 m2). CC showed a significant positive correlation with the eGFRcys/eGFRcr ratio in both sexes. The areas under the receiver operating characteristic curve were 0.725 and 0.681 for males and females, respectively. CC cutoffs with a sensitivity or specificity of 90% or 95% might be used to detect HRI in males. In conclusion, utilizing the optimum cutoff, CC could be a cost-effective screening tool for detecting HRI in elderly male patients using cystatin C as an add-on test.

We investigated the effect of antibiotic timing on outcomes based on changes in surrogate markers of organ failure, including platelet, serum bilirubin, serum creatinine levels, and the PaO₂/FiO₂ (P/F) ratio.

Type 2 diabetes mellitus represents 30-50% of the cases of end stage renal disease worldwide. Thus, a correct evaluation of renal function in patients with diabetes is crucial to prevent or ameliorate diabetes-associated kidney disease. The reliability of formulas to estimate renal function is still unclear, in particular, those new equations based on cystatin-C or the combination of creatinine and cystatin-C. We aimed to assess the error of the available formulas to estimate glomerular filtration rate in diabetic patients. We evaluated the error of creatinine and/or cystatin-C based formulas in reflecting real renal function over a wide range of glomerular filtration rate (from advanced chronic kidney disease to hyperfiltration). The error of estimated glomerular filtration rate by any equation was common and wide averaging 30% of real renal function, and larger in patients with measured glomerular filtration rate below 60 mL/min. This led to chronic kidney disease stages misclassification in about 30% of the individuals and failed to detect 25% of the cases with hyperfiltration. Cystatin-C based formulas did not outperform creatinine based equations, and the reliability of more modern algorithms proved to be as poor as older equations. Formulas failed in reflecting renal function in type 2 diabetes mellitus. Caution is needed with the use of these formulas in patients with diabetes, a population at high risk for kidney disease. Whenever possible, the use of a gold standard method to measure renal function is recommended.

Vascular dysfunction is known to be an initiator of the development and progression of cardiovascular diseases (CVDs). However, there is paucity of information on the relationship of vascular dysfunction with cardiovascular risk factors in children of African ancestry. This study investigated the relationship between cardiovascular risk factors and vascular function in South African children of African ancestry. A cross-sectional study on 6-9-year-old children in randomly selected rural and urban schools of the Eastern Cape Province of South Africa was conducted. General anthropometric indices were measured, followed by blood pressure (BP) measurements. The pulse wave velocity (PWV) was measured using a Vicorder. Albumin to creatinine ratio (ACR), asymmetric dimethylarginine (ADMA), 8-hydroxy-2deoxyguanosine (8-OHdG) and thiobarbituric acid reactive substance (TBARS) were assayed in urine. Children from urban settings (10.8%) had a higher prevalence of overweight/obesity than their rural counterparts (8.5%) while the prevalence of elevated/high blood pressure was higher in rural (23.2%) than urban children (19.0%). Mean arterial blood pressure (MAP) and diastolic blood pressure (DBP) increased with increasing PWV (p < 0.05). Body mass index (BMI), diastolic blood pressure (DBP) and mean arterial blood pressure (MAP) positively associated (p < 0.05) with PWV. Creatinine, albumin and ACR significantly (p < 0.005) increased with increasing ADMA. ADMA associated positively (p < 0.05) with creatinine and 8-OHdG. In conclusion, vascular dysfunction was associated with obesity, high blood pressure, oxidative stress and microalbuminuria in South African children of African ancestry.

Increased albuminuria is associated with increased serum ferritin, insulin resistance, and non-alcoholic fatty liver disease (NAFLD). Liver iron accumulation is also related to hyperferritinemia, insulin resistance, and NAFLD; however, there is no evidence on its relationship with albuminuria.

The association between acute kidney injury (AKI) and long-term renal function after radical nephrectomy has not been evaluated fully. We reviewed 558 cases of radical nephrectomy. Postoperative AKI was defined by the Kidney Disease: Improving Global Outcomes (KDIGO) serum creatinine criteria. Values of estimated glomerular filtration rate (eGFR) were collected up to 36 months (median 35 months) after surgery. The primary outcome was new-onset chronic kidney disease (CKD) stage 3a or higher or all-cause mortality within three years after nephrectomy. The functional change ratio (FCR) of eGFR was defined as the ratio of the most recent GFR (24-36 months after surgery) to the new baseline during 3-12 months. A multivariable Cox proportional hazard regression analysis for new-onset CKD and a multivariable linear regression analysis for FCR were performed to evaluate the association between AKI and long-term renal outcomes. A correlation analysis was performed with the serum creatinine ratio and used to determine AKI and FCR. AKI occurred in 43.2% (n = 241/558) and our primary outcome developed in 40.5% (n = 226/558) of patients. The incidence of new-onset CKD was significantly higher in patients with AKI than those without at all follow-up time points after surgery. The Cox regression analysis showed a graded association between AKI and our primary outcome (AKI stage 1: Hazard ratio 1.71, 95% confidence interval 1.25-2.32; AKI stage 2 or 3: Hazard ratio 2.72, 95% confidence interval 1.78-4.10). The linear regression analysis for FCR showed that AKI was significantly associated with FCR (β = -0.168 ± 0.322, p = 0.011). There was a significant negative correlation between the serum creatinine ratio and FCR. In conclusion, our analysis demonstrated a robust and graded association between AKI after radical nephrectomy and long-term renal functional deterioration.

Selectively targeting the E-type prostanoid receptor 4 (EP4) might be a new therapeutic option in the treatment of glomerulonephritis (GN), since the EP4 receptor is expressed on different immune cells, resident kidney cells, and endothelial cells, which are all involved in the pathogenesis of immune-complex GN. This study aimed to evaluate the therapeutic potential and to understand the mode of action of EP4 agonist in immune-complex GN using the murine model of nephrotoxic serum nephritis (NTS). In vivo, NTS mice were treated two times daily with two different doses of an EP4 agonist ONO AE1-329 or vehicle for 14 days total. The effect of PGE2 and EP4 agonism and antagonism was tested on murine distal convoluted tubular epithelial cells (DCT) in vitro. In vivo, the higher dose of the EP4 agonist led to an improved NTS phenotype, including a reduced tubular injury score and reduced neutrophil gelatinase-associated lipocalin (NGAL) and blood urea nitrogen (BUN) levels. EP4 agonist treatment caused decreased CD4+ T cell infiltration into the kidney and increased proliferative capacity of tubular cells. Injection of the EP4 agonist resulted in dose-dependent vasodilation and hypotensive episodes. The low-dose EP4 agonist treatment resulted in less pronounced episodes of hypotension. In vitro, EP4 agonism resulted in cAMP production and increased distal convoluted tubular (DCT) proliferation. Taken together, EP4 agonism improved the NTS phenotype by various mechanisms, including reduced blood pressure, decreased CD4+ T cell infiltration, and a direct effect on tubular cells leading to increased proliferation probably by increasing cAMP levels.