Changes In Serum Creatinine Levels Research Articles

Evaluation of efficacy and safety of DPP-4 inhibitors for Chinese elderly patients with type 2 diabetes mellitus

BackgroundThe safety of hypoglycemic drugs should be paid more attention to in elderly patients with type 2 diabetes mellitus due to their concomitant diseases, physiological decline of liver and kidney function and cognitive decline. The aim of this study was to evaluate the efficacy and safety of DPP-4 inhibitors in elderly patients with type 2 diabetes mellitus.MethodsFrom January 2010 to November 2018, 300 patients with type 2 diabetes mellitus who were over 60 years old were enrolled in the outpatient clinic of Geriatric Medical Center. Their medication records and follow-up medical records were used for retrospective analysis. The duration of treatment with DPP-4 inhibitors was more than 3 months. The changes of fasting blood glucose (GLU), glycosylated hemoglobin (HbA1C), body weight, body mass index (BMI) and liver and kidney function were compared before and after treatment.ResultsThe average age of 300 patients (212 males and 88 females) was 73.7 ± 9.1 years old, BMI was 26.5 ± 2.8 kg/m2 and the duration of diabetes was 10.7 ± 8.2 years. The results of retrospective analysis showed that HbA1C decreased by 0.27% after treatment (P < 0.001). In the group of DPP-4 inhibitors used for less than 12 months, there was no difference in liver transaminase (ALT and AST) between before and after treatment, whereas in the group of DPP-4 inhibitors used formore than 12 months, liver transaminase decreased statistically compared with after treatment (P < 0.001). The incidence of fatty liver in elderly diabetic patients decreased after using DPP-4 inhibitors. There was no significant change in serum creatinine level and creatinine clearance rate in elderly patients with type 2 diabetes mellitus after treatment of DPP-4 inhibitor. In addition, the body weight and BMI of the patients decreased significantly (P < 0.001). No hypoglycemic reaction and gastrointestinal discomfort were found in the medical records.ConclusionAfter DPP-4 inhibitors were used in elderly patients with type 2 diabetes mellitus, the elevated glycosylated hemoglobin could be controlled with improved safety of liver and kidney, and might have the effect of weight loss.

Changes in Serum Creatinine Levels and Natural Evolution of Acute Kidney Injury with Conservative Management of Hemodynamically Significant Patent Ductus Arteriosus in Extremely Preterm Infants at 23-26 Weeks of Gestation.

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.

Erythropoietin Attenuation Of Early Upregulation Of Kidney Injury Parameters Levels In Cisplatin-Treated Rats..

Background: cisplatin chemotherapy can cause acute kidney injury (AKI) in about 30% of patients that act as a major dose-limiting problem complicating chemotherapy by cisplatin that still commonly indicated as first line treatment of cancer management without relatively less toxic and equally effective substitutes. Cisplatin induced-DNA damage and oxidative- inflammatory hyper-reactivity with apoptosis are the bases for cisplatin-induced AKI. Erythropoietin has approved antioxidant, anti-inflammatory and to some extent antiapoptotic effects that may have ameliorative effect on early cisplatin-induced AKI. Kidney injury molecules-1 (KIM-1) and interleukin-18 (IL-18) were assumed to be more sensitive for detecting AKI than the traditional kidney function tests (serum creatinine and urea). Objective: assess the effect of erythropoietin on early upregulation of kidney injury parameters after cisplatin treatment. Methods: 27 adult male rats were randomized into three groups containing nine rats for each as follow: Sham group: rats received daily intraperitoneal injection of placebo for 4 days. Cisplatin group: rats received single intraperitoneal injection of 6 mg kg cisplatin. Cisplatin+Erythropoietin group: rats received single intraperitoneal injection of 6 mg kg cisplatin and daily intraperitoneal injection of 100 IU kg erythropoietin for 4 days. After scarification, blood samples are collected for serum creatinine measurement, kidneys are processed for measurement of renal MDA, KIM-1 and IL-18 and histopathlogical evaluation. Results: cisplatin produced significant (P<0.05) change in serum creatinine level, kidney MDA, KIM-1, IL-18 and score of histopathological damage severity when compared to that of other groups. In Cisplatin + Erythropoietin group, Serum creatinine, and kidney MDA, KIM-1, IL-18 and total severity score were significantly (P<0.05) less than that in cisplatin group. Conclusion: erythropoietin ameliorated early cisplatin–induced AKI evidenced by improving early injury parameters that give rise for early involvement of erythropoietin as early preventive measure for protection from nephrotoxicity.

Effectiveness and Safety of Hydroxychloroquine compared to Teneligliptin in uncontrolled T2DM patients as add-on Therapy.

ObjectivesHydroxychloroquine (HCQ) 400 mg is approved by the Drug Controller General of India (DCGI) and recommended by the Research Society for the Study of Diabetes in India (RSSDI) clinical practice recommendations 2017 as add-on therapy after metformin and sulfonylurea in Type 2 Diabetes (T2DM) patients. The aim of this observational study is to compare the efficacy and safety of hydroxychloroquine 400 mg and teneligliptin 20 mg when used as add-on therapy in Indian Type 2 DM patients who were inadequately controlled (HbA1c ≥7.5%) with metformin 1000 mg and glimepiride 2 mg combination.MethodologyThis study is a prospective observational study to be conducted in 2 diabetic centres of Patna city between October 2017 and May 2018 involving 180 patients followed up for 6 months. One group (N=90) of patients received hydroxychloroquine 400 mg + metformin 1000 mg + glimepiride 2 mg, the other group (N=90) received teneligliptin 20 mg + metformin 1000 mg + glimepiride 2 mg. Efficacy was assessed by fasting blood glucose (FBG), post prandial blood glucose (PPBG) and glycated haemoglobin (HbA1c) reduction. Safety was evaluated by the number of hypoglycaemic events and changes in serum creatinine levels. Home based glucose monitoring was used to detect the hypoglycaemic events. Patients who had any type of retinopathy/maculopathy were excluded.ResultsMean age of entire population was 66±8 years with mean 6±2 years of DM with 102 males. Mean body weight was 71±12 kg. Baseline HbA1c was 8.1±0.3 in the hydroxychloroquine group and 8.2±0.2 in the teneligliptin group.At 24 weeks there were statistically significant reductions in mean HbA1c in the hydroxychloroquine group (1.1±0.3) as compared to the teneligliptin group (0.82±0.3) (P≤0.001). The mean FBG and PPBG was 169±18 mg/dl and 232±18 mg/dl respectively in hydroxychloroquine group which was reduced to 121±15 mg/dl and 161±19 mg/dl at the end of 24 weeks. In the teneligliptin group, FBG and PPBG was 171±16 mg/dl and 239±21 mg/dl at baseline, which was reduced to 121±15 mg/dl and 161±19 mg/dl respectively in same period of time (P≤ 0.005). There were 4 incidences of hypoglycaemic events in the hydroxychloroquine group (4.4%) and 6 in the teneligliptin group (6.67%). No patients required medical assistance for hypoglycaemic events. There was no statistically significant change in body weight in both the groups. No marked changes in creatinine levels were found in patients in both the groups.ConclusionIn conclusion, treatment with hydroxychloroquine 400 mg for 24 weeks reduces glycaemic parameters more aggressively than teneligliptin 20 mg in Indian type 2 diabetes patients.

Renal impact of high-loading-dose statin pre-cardiac catheterization in patients with chronic kidney disease and long-term statin use.

Previous studies have reported that short-term statin loading effectively protects statin-naive patients with mild renal insufficiency from contrast-induced acute kidney injury (CI-AKI). The aim of the present study was to determine whether patients with more advanced chronic kidney disease (CKD) and long-term statin therapy also benefit from high-loading statin pretreatment. A total of 256 consecutive patients with moderate-to-severe CKD receiving long-term statin therapy and undergoing percutaneous coronary intervention (PCI) or coronary artery angiography (CAG) were divided into the statin-loading group (n=34) and the no statin-loading group (n=222), depending on whether the respective patient received high-dose statin within 24 h prior to the intervention. The primary endpoint was the percent change in serum creatinine (SCr) levels. Additional endpoints included absolute change in SCr levels, estimated glomerular filtration rate (eGFR) at 48–72 h after contrast exposure, incidence rate of CI-AKI and composite in-hospital adverse events. The mean SCr decreased from baseline in either of the two groups, and the differences in the percent (P=0.930) and absolute change (P=0.990) in SCr levels were not significant between the two groups. Furthermore, no significant difference in the post-procedural eGFR was observed between the two groups. The incidence rates of CI-AKI (2.9 vs. 4.1%, P>0.999) and in-hospital adverse events (0.0 vs. 3.6%, P=0.602) were also similar between the two groups. Stratified analyses were then performed, which yielded results consistent with the above. Multiple linear regression indicated that the baseline eGFR value and current smoking status were independent factors affecting the post-procedural eGFR value, while high-dose statin loading was not. Therefore, statin reloading prior to intervention may not provide any further renal protection or decrease the occurrence of in-hospital adverse events in patients with moderate-to-severe CKD receiving long-term statin therapy, which warrants validation in prospective trials.

Comparison of renal safety of tenofovir and entecavir in patients with chronic hepatitis B: Systematic review with meta-analysis

BACKGROUNDRecently, the American Association for the Study of Liver Disease suggested no preference between tenofovir (TDF) and entecavir (ETV) regarding potential long-term risks of renal complications. Over the years, renal safety has become a critical concern in nucleos(t)ide analog-treated patients due to the long-term use of these drugs. However, existing studies do not show significant differences in renal dysfunction between these two drugs. Further, there is a paucity of studies comparing the long-term renal effects of TDF and ETV.AIMTo investigate the effects of TDF and ETV on renal function, we performed systematic review and meta-analysis.METHODSTwo investigators independently searched the Cochrane Library, MEDLINE, and Embase databases for randomized controlled trials and nonrandomized studies (NRSs) using the keywords “CHB”, “Tenofovir”, and “Entecavir”, and additional references were obtained from the bibliographies of relevant articles published through December 2017. The quality of each study was assessed using the Newcastle-Ottawa scale and the Grading of Recommendations Assessment, Development and Evaluation criteria. The primary outcome was the change in serum creatinine level in the TDF and ETV groups at baseline, 6 mo, 12 mo and 24 mo.RESULTSNine NRSs comprising 2263 participants met the inclusion criteria. Changes in creatinine levels were higher in the TDF group than in the ETV group at 6 mo [mean difference (MD) = 0.03 mg/dL; 95%CI: 0.02-0.04; I2 = 0%], 12 mo (MD = 0.05 mg/dL; 95%CI: 0.02-0.08; I2 = 78%), and 24 mo (MD = 0.07 mg/dL; 95%CI: 0.01-0.13; I2 = 93%). The change in estimated glomerular filtration rate (eGFR) was significantly higher in the TDF group than in the ETV group at 6 mo [standardized mean difference (SMD), -0.22; 95%Cl: -0.36--0.08; I2 = 0%], 12 mo (SMD = -0.24; 95%Cl: -0.43--0.05; I2 = 50%), and 24 mo (-0.35; 95%Cl: -0.61- -0.09; I2 = 67%).CONCLUSIONTDF statistically significantly increased serum creatinine levels and decreased the eGFR in 6-24 mo compared to ETV, with moderate to low quality of evidence. However, the differences are negligible.

Safety and Efficacy of Bilateral Simultaneous Percutaneous Nephrolithotomy

Background: To evaluate the safety and efficacy of bilateral simultaneous percutaneous nephrolithotomy in one tertiary hospital in Nepal.Methods: Retrospective study was done for all patients that underwent bilateral simultaneous percutaneous nephrolithotomy in our center from January 2010 to December 2017. The study included 36 male and 16 female patients with totalof 104renal units at an average age of 37 years (range 3 -65 years). Five patients were planned for bilateral simultaneous Percutaneous nephrolithotomy, but intraoperatively the procedure was aborted after completion of only one side due to various factors. All PCNL were performed in prone position under general anesthesia.Results: In91.2% of the patients, bilateral simultaneous percutaneous nephrolithotomy could be performed as planned. Average time required for bilateral simultaneous percutaneous nephrolithotomy was 94 ± 38.8mins (range 25 – 170 mins) with average hemoglobin drop of 1.85 ± 1.30gm% (range 0.1 - 4.2gm%) and no significant change in serum creatinine levels. Multiple access tracts (&gt;1) had to be created in 3 renal units. Most of the renal stones were Guy’s stone score (GSS) 1 and 2 whereas 15.4% were GSS of 3 and 4.Overall stone free rate was 94% with significant residual stones (&gt;4mm) in 6 renal units which were subjected to extracorporeal shockwave lithotripsy (SWL) on a later date (Clavien-Dindo Grade: III-a). Bladder clot evacuation was done in one patient (Clavien-Dindo Grade: III-b). Blood transfusion was required in two patients and two patients developed postoperative sepsis (Clavien-Dindo Grade: II). One patient developed hydrothorax which was managed successfully (Clavien-Dindo Grade: III-a). Conclusions: Bilateral simultaneous Percutaneous nephrolithotomy is feasible and safe procedure, given that the patients are appropriately selected based upon Guy’s stone score, stone burden, pelvi-calyceal anatomy and overall health status.Keywords: Bilateral simultaneous;endourology; percutaneous nephrolithotomy; urolithiasis.

Safety and Efficacy of Bilateral Simultaneous Percutaneous Nephrolithotomy.

To evaluate the safety and efficacy of bilateral simultaneous percutaneous nephrolithotomy in one tertiary hospital in Nepal. Retrospective study was done for all patients that underwent bilateral simultaneous percutaneous nephrolithotomy in our center from January 2010 to December 2017. The study included 36 male and 16 female patients with totalof 104renal units at an average age of 37 years (range 3 -65 years). Five patients were planned for bilateral simultaneous Percutaneous nephrolithotomy, but intraoperatively the procedure was aborted after completion of only one side due to various factors. All PCNL were performed in prone position under general anesthesia. In91.2% of the patients, bilateral simultaneous percutaneous nephrolithotomy could be performed as planned. Average time required for bilateral simultaneous percutaneous nephrolithotomy was 94 ± 38.8mins (range 25 - 170 mins) with average hemoglobin drop of 1.85 ± 1.30gm% (range 0.1 - 4.2gm%) and no significant change in serum creatinine levels. Multiple access tracts (>1) had to be created in 3 renal units. Most of the renal stones were Guy's stone score (GSS) 1 and 2 whereas 15.4% were GSS of 3 and 4.Overall stone free rate was 94% with significant residual stones (>4mm) in 6 renal units which were subjected to extracorporeal shockwave lithotripsy (SWL) on a later date (Clavien-Dindo Grade: III-a). Bladder clot evacuation was done in one patient (Clavien-Dindo Grade: III-b). Blood transfusion was required in two patients and two patients developed postoperative sepsis (Clavien-Dindo Grade: II). One patient developed hydrothorax which was managed successfully (Clavien-Dindo Grade: III-a). Bilateral simultaneous Percutaneous nephrolithotomy is feasible and safe procedure, given that the patients are appropriately selected based upon Guy's stone score, stone burden, pelvi-calyceal anatomy and overall health status.

Assessing the nephrotoxicity of intravenous iodinated contrast agents in patients with chronic renal failure in the absence of interfering acute disease

Background The existence of contrast-induced nephropathy is widely accepted. Recent studies suggest its incidence has been overestimated. Purpose To determine the effect of intravenous iodinated contrast agents on renal function in patients with chronic renal failure without acute disease that can interfere with the assessment of renal function. Material and Methods We prospectively analyzed changes in serum creatinine levels after intravenous administration of iodinated contrast agents in all patients with chronic renal failure (creatinine clearance &lt; 60 mL/min by the CKD-EPI Equation) without acute disease referred for computed tomography (CT) follow-up of aortic aneurysm. Between March 2010 and December 2016, a total of 108 patients met the inclusion criteria. The first 35 patients randomly underwent both contrast-enhanced and unenhanced CT examinations six months apart; the 73 following patients underwent only contrast-enhanced CT examinations. Serum creatinine levels were recorded immediately before and 48–72 h after CT examinations. Contrast-induced nephropathy was defined as an increase of ≥25% in serum creatinine from baseline levels. Results In the first 35 patients, mean changes in creatinine levels after unenhanced and enhanced CT examinations were similar. From the total of 108 patients who underwent contrast-enhanced CT, serum creatinine increased &gt; 25% with respect to baseline in only two patients, in one case after contrast-enhanced CT examination and in the other after unenhanced CT examination; in a third patient, serum creatinine decreased &gt;25% after contrast-enhanced CT examination. Conclusion No relevant contrast-induced nephrotoxicity was detected in this group of patients with chronic renal failure without acute disease.

Acute kidney injury in Indigenous Australians in the Kimberley: age distribution and associated diagnoses.

To describe the frequencies of acute kidney injury (AKI) and of associated diagnoses in Indigenous people in a remote Western Australian region. Retrospective population-based study of AKI events confirmed by changes in serum creatinine levels. Aboriginal and Torres Strait Islander residents of the Kimberley region of Western Australia, aged 15 years or more and without end-stage kidney disease, for whom AKI between 1 June 2009 and 30 May 2016 was confirmed by an acute rise in serum creatinine levels. Age-specific AKI rates; principal and other diagnoses. 324 AKI events in 260 individuals were recorded; the median age of patients was 51.8 years (IQR, 43.9-61.0 years), and 176 events (54%) were in men. The overall AKI rate was 323 events (95% CI, 281-367) per 100000 population; 92 events (28%) were in people aged 15-44 years. 52% of principal diagnoses were infectious in nature, including pneumonia (12% of events), infections of the skin and subcutaneous tissue (10%), and urinary tract infections (7.7%). 80 events (34%) were detected on or before the date of admission; fewer than one-third of discharge summaries (61 events, 28%) listed AKI as a primary or other diagnosis. The age distribution of AKI events among Indigenous Australians in the Kimberley was skewed to younger groups than in the national data on AKI. Infectious conditions were common in patients, underscoring the significance of environmental determinants of health. Primary care services can play an important role in preventing community-acquired AKI; applying pathology-based criteria could improve the detection of AKI.

Disrupted tubular parathyroid hormone/parathyroid hormone receptor signaling and damaged tubular cell viability possibly trigger postsurgical kidney injury in patients with advanced hyperparathyroidism.

BackgroundParathyroidectomy (PTX) that alleviates clinical manifestations of advanced hyperparathyroidism, including hypercalcemia and hypophosphatemia, is considered the best protection from calcium overload in the kidney. However, little is known about the relationship between postsurgical robust parathyroid hormone (PTH) reduction and perisurgical renal tubular cell viability. Post-PTX kidney function is still a crucial issue for primary hyperparathyroidism (PHPT) and tertiary hyperparathyroidism after kidney transplantation (THPT).MethodsAs a clinical study, we examined data from 52 consecutive patients (45 with PHPT, 7 with THPT) who underwent PTX in our center between 2015 and 2017 to identify post-PTX kidney injury. Their clinical data, including urinary liver-type fatty acid-binding protein (L-FABP), a tubular biomarker for acute kidney injury (AKI), were obtained from patient charts. An absolute change in serum creatinine level of 0.3 mg/dL (26.5 µmol/L) on Day 2 after PTX defines AKI. Post-PTX calcium supplement dose adjustment was performed to strictly maintain serum calcium at the lower half of the normal range. To mimic post-PTX-related kidney status, a unique parathyroidectomized rat model was produced as follows: 13-week-old rats underwent thyroparathyroidectomy (TPTX) and/or 5/6 subtotal nephrectomy (NX). Indicated TPTX rats were given continuous infusion of a physiological level of 1-34 PTH using a subcutaneously implanted osmotic minipump. Immunofluorescence analyses were performed by polyclonal antibodies against PTH receptor (PTHR) and a possible key modulator of kidney injury, Klotho.ResultsPatients’ estimated glomerular filtration rate (eGFR) did not have any clinically relevant change (62.5 ± 22.0 versus 59.4 ± 21.9 mL/min/1.73 m2, NS), whereas serum calcium (2.7 ± 0.18 versus 2.2 ± 0.16 mmol/L, P < 0.0001) and phosphorus levels (0.87 ± 0.19 versus 1.1 ± 0.23 mmol/L, P < 0.0001) were normalized and PTH decreased robustly (181 ± 99.1 versus 23.7 ± 16.8 pg/mL, P < 0.0001) after successful PTX. However, six patients who met postsurgical AKI criteria had lower eGFR and greater L-FABP than those without AKI. Receiver operating characteristics (ROC) analysis revealed eGFR <35 mL/min/1.73 m2 had 83% accuracy. Strikingly, L-FABP >9.8 µg/g creatinine had 100% accuracy in predicting post-PTX-related AKI. Rat kidney PTHR expression was lower in TPTX. PTH infusion (+PTH) restored tubular PTHR expression in rats that underwent TPTX. Rats with TPTX, +PTH and 5/6 NX had decreased PTHR expression compared with those without 5/6 NX. 5/6 NX partially cancelled tubular PTHR upregulation driven by +PTH. Tubular Klotho was modestly expressed in normal rat kidneys, whereas enhanced patchy tubular expression was identified in 5/6 NX rat kidneys. This Klotho and expression and localization pattern was absolutely canceled in TPTX, suggesting that PTH indirectly modulated the Klotho expression pattern. TPTX +PTH recovered tubular Klotho expression and even triggered diffusely abundant Klotho expression. 5/6 NX decreased viable tubular cells and eventually downregulated tubular Klotho expression and localization.ConclusionsPreexisting tubular damage is a potential risk factor for AKI after PTX although, overall patients with hyperparathyroidism are expected to keep favorable kidney function after PTX. Patients with elevated tubular cell biomarker levels may suffer post-PTX kidney impairment even though calcium supplement is meticulously adjusted after PTX. Our unique experimental rat model suggests that blunted tubular PTH/PTHR signaling may damage tubular cell viability and deteriorate kidney function through a Klotho-linked pathway.

Incidence, Risk Factors, and Clinical Outcomes of Acute Kidney Injury Caused by Palliative Chemotherapy in Lung Cancer.

Purpose: Acute kidney injury (AKI) affects cancer therapy outcome and increases morbidity and mortality in cancer patients. We investigated the incidence, risk factors, and clinical outcomes of AKI caused by palliative chemotherapy in lung cancer patients.Materials and Methods: Between January 2005 and November 2014, 207 lung cancer patients who had been treated with first-line palliative chemotherapy were enrolled. Renal function was assessed during every cycle of chemotherapy. AKI was defined based on changes in serum creatinine levels as described in the Kidney Disease: Improving Global Outcomes guidelines. Clinical outcomes were evaluated depending on AKI occurrence during the first-line chemotherapy.Results: Of the 207 patients, 36 (17.4%) experienced AKI. Among the 36 patients who developed AKI during chemotherapy, 33 (91.8%) had AKI stage I. Although 19 patients (52.7%) with AKI during chemotherapy progressed to chronic kidney disease (CKD), no patients were reported to progress to end-stage renal disease (ESRD). The number of chemotherapy cycles was independently associated with chemotherapy-induced AKI in multivariate analysis (OR = 1.71, 95% CI 1.29-2.26, p < 0.001). The median follow-up duration was 83 months. Patients with AKI during chemotherapy (AKI group) showed significantly longer time to treatment failure than patients without AKI (non-AKI group) (4.2 vs. 2.5 months, p < 0.001). However, the median overall survival (11.7 vs. 8.8 months, p = 0.147) and progression-free survival (5.5 vs. 5.2 months, p = 0.347) were not different between the groups.Conclusions: AKI that developed during chemotherapy was mostly of mild degree and its prognosis was favorable. The occurrence of AKI was associated with the number of chemotherapy cycles administered. AKI did not adversely affect survival of lung cancer patients during chemotherapy.

Combination of Nonwoven Filters and Mesenchymal Stem Cells Reduced Glomerulosclerotic Lesions in Rat Chronic Kidney Disease Models

Background and Objectives: The increasing incidence of patients requiring hemodialysis has become a medical and economic problem globally; it is necessary to maintain renal glomerulus functionality to prevent the progression of chronic kidney disease. As a therapeutic tool for preventing the progression of chronic kidney disease, mesenchymal stem cells (MSCs) are a promising source of both growth factors and cells for regeneration. However, the escape of MSCs from injection sites, as well as the insufficient production of growth factors, is issues that remain unresolved. In the present study, a complex of cells and a nonwoven filter was localized in an injured kidney to provide growth factors such as vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF). Methods and Results: Nonwoven biodegradable polylactic acid (PLA) filters were used to capture rat bone marrow stem cells (r-BMSCs). The capture rates of r-BMSCs on five PLA filter disks were over 85%. The production of HGF by r-BMSCs on PLA filters was markedly enhanced through interactions between the cells and the nonwoven filter. Conversely, the production of VEGF by r-BMSC on PLA filters was unchanged. Complexes of nonwoven filters and cells were implanted onto the surfaces of kidneys of 5/6-nephrectomized rats, which are characterized by progressive glomerulosclerosis. Within the r-BMSC/PLA complexes, deleterious changes in serum creatinine levels were not attenuated. However, PLA filters with r-BMSCs, which enhanced HGF production over 4 weeks of culture, significantly (P = 0.03) decreased urinary protein levels at 4 weeks after implantation compared to untreated nephrectomized rats. Further histopathological studies revealed that glomerulosclerotic lesions were significantly (P = 0.008) reduced by treatment with the r-BMSC/PLA complex. Conclusion: Devices made of PLA nonwoven filters and stem cells are potentially useful for the prevention and treatment of chronic kidney disease.

Orthotopic renal autotransplantation for young-onset and medical treatment-requiring complex renovascular hypertension.

Objective:In this article, we aim to prove the safety and effectiveness of orthotopic renal autotransplantation using ex vivo repair for the treatment of complex renovascular hypertension (RVH).Methods:We retrospectively reviewed five consecutive patients (three women, two men) with young-onset RVH from January 2009 to August 2014. Orthotopic renal autotransplantation using ex vivo repair was performed and perioperative data were collected for statistical analysis.Results:The median age at diagnosis was 20 years (range, 11 to 27 years). Technique success was achieved in all the patients with no in-hospital or late deaths. During a median follow-up of 3.4 years (range, 1.5 to 6 years), the postoperative blood pressure was decreased compared with preoperative level (204 ± 8/133 ± 8 mm Hg vs 129 ± 3/78 ± 5 mm Hg; p < 0.0001). The postoperative anti-hypertensive medications number was reduced (3.4 ± 0.4 vs 0.2 ± 0.2; p < 0.0001). Early and late renal functions were both well preserved as measured by no changes in serum creatinine level (p > 0.05). The primary patent rate was 100% (5/5) at one-year follow-up.Conclusion:In our small series, orthotopic renal autotransplantation using ex vivo repair was safe and effective for the resolution of complex young-onset RVH.

Aldosterone Antagonist Therapy and Mortality in Patients With ST-Segment Elevation Myocardial Infarction Without Heart Failure

Treatment with aldosterone antagonists is recommended and has been shown to have beneficial effects in patients with ST-segment elevation myocardial infarction (STEMI) and left ventricular ejection fraction (LVEF) less than 40%. However, the role of aldosterone antagonists in patients with ejection fraction greater than 40% or without congestive heart failure is not well known. To perform a systematic review and meta-analysis using standard techniques to determine the role of therapy with aldosterone antagonists in this patient population. PubMed, Embase, CINAHL, and Cochrane Central databases were searched and a manual search for relevant references from the selected articles and published reviews was performed from database inception through June 2017. Randomized clinical trials that evaluated treatment with aldosterone antagonists in patients with STEMI without clinical heart failure or LVEF greater than 40% were included. Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were used to conduct and report the meta-analysis, which used a random-effects model. Two investigators independently performed the database search and agreed on the final study selection. A manual search was performed for relevant references from the selected articles and published reviews. The outcomes analyzed were mortality, new congestive heart failure, recurrent myocardial infarction, ventricular arrhythmia, and changes in LVEF, serum potassium level, and creatinine level at follow-up. In all, 10 randomized clinical trials with a total of 4147 unique patients were included in the meta-analysis. In patients who presented with STEMI without heart failure, treatment with aldosterone antagonists compared with control was associated with lower risk of mortality (2.4% vs 3.9%; odds ratio [OR], 0.62; 95% CI, 0.42-0.91; P = .01) and similar risks of myocardial infarction (1.6% vs 1.5%; OR, 1.03; 95% CI, 0.57-1.86; P = .91), new congestive heart failure (4.3% vs 5.4%; OR, 0.82; 95% CI, 0.56-1.20; P = .31), and ventricular arrhythmia (4.1% vs 5.1%; OR, 0.76; 95% CI, 0.45-1.31; P = .33). Similarly, treatment with aldosterone antagonists compared with control was associated with a small yet significant increase in LVEF (mean difference, 1.58%; 95% CI, 0.18%-2.97%; P = .03), a small increase in serum potassium level (mean difference, 0.07 mEq/L; 95% CI, 0.01-0.13 mEq/L; P = .02), and no change in serum creatinine level (standardized mean difference, 1.4; 95% CI, -0.43 to 3.24; P = .13). Treatment with aldosterone antagonists is associated with a mortality benefit in patients with STEMI with LVEF greater than 40% or without heart failure.

No Reported Renal Stones with Intravenous Vitamin C Administration: A Prospective Case Series Study

A few cases associating high dose intravenous vitamin C (IVC) administration with renal stone formation have been reported in the literature, however, no long-term studies investigating IVC administration and reported renal stones have been carried out. Our aim was to measure the frequency of reported renal stones in patients receiving IVC therapy. We carried out a prospective case series study of 157 adult patients who commenced IVC therapy at Integrated Health Options clinic between 1 September 2011 and 31 August 2012, with follow-up for 12 months. Inquiries into the occurrence of renal stones were conducted at enrolment, 6 and 12 months, and renal function blood tests were conducted at enrolment, 4 weeks and every 12 weeks thereafter in a subgroup of patients. No renal stones were reported by any patients in the study, despite 8% of the patients having a history of renal stones. In addition, the majority of patients investigated had stable renal function during the study period as evidenced by little change in serum creatinine levels and estimated glomerular filtration rate (eGFR) following IVC. In conclusion, IVC therapy was not associated with patient-reported renal stones. Although not the primary focus of this study, it was also observed that there was no significant change in mean serum creatinine or eGFR for those who had follow-up renal function blood tests.

Paradigms of acute kidney injury in the intensive care setting.

Acute kidney injury (AKI) is a heterogeneous clinical syndrome that has multiple aetiologies, variable pathogenesis and diverse outcomes. However, these heterogeneities are not reflected in current approaches to the diagnosis and, to some degree, treatment of AKI. For example, congestive heart failure and dehydration can produce identical changes in serum creatinine level and urine output (parameters that are used to define AKI); however, they differ vastly in their physiological contexts and demand completely opposite treatments. AKI is often still considered to be a homogeneous clinical entity, which implies a uniform pathogenesis and a well-defined prognosis. As a consequence, efforts to find effective AKI treatments have been hampered by a lack of clear clinical classifications for various types of AKI. In addition, subclassification of AKI into subclinical phenotypes - for example, on the basis of protein biomarkers and other in vitro diagnostics that take into account disease aetiology and underlying pathogenesis - might be necessary to develop therapeutic approaches that effectively target the widely differing pathomechanisms of AKI. In this Review, we discuss the major subtypes of AKI that are associated with sepsis, major surgery, renal hypoperfusion and nephrotoxin exposure -situations that are typically seen in the intensive care setting. We consider differences and similarities in their phenotype, pathogenesis and outcomes and how this information might be used to guide treatment.

Goal-directed therapy in patients with early acute kidney injury: a multicenter randomized controlled trial

OBJECTIVES:Acute kidney injury is associated with many conditions, and no interventions to improve the outcomes of established acute kidney injury have been developed. We performed this study to determine whether goal-directed therapy conducted during the early stages of acute kidney injury could change the course of the disease.METHODS:This was a multicenter prospective randomized controlled study. Patients with early acute kidney injury in the critical care unit were randomly allocated to a standard care (control) group or a goal-directed therapy group with 8h of intensive treatment to maximize oxygen delivery, and all patients were evaluated during a period of 72h. ClinicalTrials.gov: NCT02414906.RESULTS:A total of 143 patients were eligible for the study, and 99 patients were randomized. Central venous oxygen saturation was significantly increased and the serum lactate level significantly was decreased from baseline levels in the goal-directed therapy group (p=0.001) compared to the control group (p=0.572). No significant differences in the change in serum creatinine level (p=0.96), persistence of acute kidney injury beyond 72h (p=0.064) or the need for renal replacement therapy (p=0.82) were observed between the two groups. In-hospital mortality was significantly lower in the goal-directed therapy group than in the control group (33% vs. 51%; RR: 0.61, 95% CI: 0.37-1.00, p=0.048, number needed to treat=5).CONCLUSIONS:Goal-directed therapy for patients in the early stages of acute kidney injury did not change the disease course.

The effect of establishing pre-angiography thresholds on contrast utilization.

Contrast induced nephropathy is linked to contrast utilization and strategies for minimizing renal injury are incorporated into many laboratories that perform coronary angiography. Contrast limits have been described, below which there is minimal incremental increase in the risk of renal injury. Whether a priori acknowledgement of these limits as part of a contrast "Time-Out" reduces contrast utilization has not been established. In this study, we investigate the effect of verbalizing pre-angiography and ½ time contrast thresholds on contrast utilization and associated clinical outcomes. We retrospectively reviewed 5265 cases of coronary angiography (984 with contrast thresholds defined pre-procedure compared to 4281 without pre-defined contrast thresholds). There were two primary endpoints: (1) proportion of procedures that utilized an amount of contrast ≤ threshold, and (2) median difference between amount of contrast utilized and the contrast threshold. Secondary outcomes incorporated indices of renal function, and included changes in serum creatinine levels, eGFR, and CKD stage. Compared to pre-"Time-Out" group, the post-"Time-Out" group had a higher proportion of procedures with contrast ≤ stated contrast threshold (88% vs 84%, P < 0.002), and a lower amount of total contrast volume (88 mL [IQR 60-136] versus 78 mL [IQR 53-119]). The post-"Time-Out" group also had a lower incidence of any increase in post-procedure serum creatinine (45% vs 36%; P = 0.04), and a larger median decrease of pre- to post-procedure eGFR (P = 0.04). Acknowledgement of contrast threshold as part of a contrast "Time-Out" is associated with reduced overall contrast utilization, and likely minimizes risks of contrast-induced nephropathy.

Blood Conservation Using Tranexamic Acid Is Not Superior to Epsilon-Aminocaproic Acid After Total Knee Arthroplasty.

Epsilon-aminocaproic acid (EACA) and tranexamic acid (TXA) are synthetic amino acid derivatives that interfere with fibrinolysis, promoting hemostasis by pharmacological means. Although both drugs have been shown to decrease blood loss with a minimal risk of thromboembolic adverse events following cardiac and vascular surgery, we are aware of only 1 published trial that directly compared the antifibrinolytic effects of EACA with those of TXA after total knee arthroplasty (TKA). The primary aim of this prospective, randomized, controlled trial was to determine whether TXA provides superior blood conservation following TKA compared with that provided by EACA. A total of 194 patients scheduled to undergo a primary unilateral TKA in the same community-based hospital were prospectively randomized to receive intravenous EACA (n = 96) or TXA (n = 98). Both the patients and the operating surgeons were blinded to the treatment assignments. Primary outcome measures included transfusions, estimated blood loss, and the drop in the hemoglobin (Hgb) level. Secondary outcomes measures included the change in the serum creatinine level, postoperative complications, and length of hospital stay. Although the patients who received TXA averaged less estimated blood loss than the patients who received EACA (t185 = 2.18, p = 0.031; mean difference = 144.2 mL, 95% confidence interval = 13.62 to 274.78 mL), no transfusions were required in either group. We observed no statistically significant or clinically relevant between-group differences in the change in Hgb or serum creatinine level, postoperative complications, or length of hospital stay. Although the estimated blood loss was significantly greater in the EACA group, no transfusions were required and no significant between-group differences were observed for any other outcomes measured. We concluded that EACA may be an acceptable alternative to TXA for blood conservation following TKA, although replication of our results in noninferiority trials is necessary. Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.