Glomerular Filtration Rate Stage Research Articles

#444 Novel MRI filtration fraction method to assess glomerular hemodynamics in diabetic kidney disease

Abstract Background and Aims Filtration fraction (FF) is the ratio of the glomerular filtration rate (GFR) to renal plasma flow (RPF) and is therefore an important measure of glomerular hemodynamics. The gold standard method to assess effective RPF is renal clearance of para-aminohippuric acid (PAH) but technical and labour-intensive difficulties limit its application [1]. Quicker and simpler assays of FF are needed, particularly to assess the renal hemodynamic dysfunction (hyper- or hypofiltration) and effects/mode of action of therapeutic interventions in chronic kidney disease (CKD). We assessed a novel magnetic resonance imaging (MRI) technique to measure FF in patients with diabetic kidney disease (DKD) and healthy controls (HC) [2]. Method This cross-sectional sub-study included 32 DKD subjects with measured GFR (mGFR) ≤ 60 ml/ min/1.73 m2 and stratified into the following GFR stages as per the Kidney Disease Improving Global Outcomes (KDIGO) classification: stage G3a (mGFR 45-59 ml/ min/1.73 m2, n = 3), G3b (mGFR 30-44 ml/ min/1.73 m2, n = 8), G4 (mGFR 15-29 ml/ min/1.73 m2, n = 15), G5 (<15 ml/ min/1.73 m2, n = 6), and 18 age-, gender-matched HC with mGFR ≥ 60 ml/min/1.73 m2. All subjects were 18-79 years old. mGFR was assessed using iohexol clearance. Renal blood flow (RBF) (ml/min) was measured by a 5-minute add-on phase contrast MRI of the renal artery of each kidney and then summed together. RBF was corrected for Body Surface Area. RPF and FF were calculated as below: ${\rm{RPF }} = {\rm{ RBF}} \times \ ( {1\ -{\rm{ Hematocrit}}} )$ ${\rm{FF}} = {\rm{mGFR}}/{\rm{RPF}}$ Results RBF and mGFR were highly correlated (R2 = 0.70, Fig. 1). FF was 17.1% for HC and decreased with increasing degrees of renal impairment (Fig. 2). While the difference between HC and G3a DKD group was not significant, there was highly significant difference between HC and all other DKD groups (p < 0.001). The standard deviation in the G3a group was relatively large with only 3 subjects in this group. Conclusion The phase contrast MRI scan can provide a quick and simple measurement of glomerular hemodynamics and therewith further insights into the pathophysiology of DKD and its progression. Given the limitations of the existing method for assessing renal plasma flow, this MRI method can facilitate the inclusion of filtration fraction in DKD clinical trials. Further, the described method could be used to identify hyperfiltration, a compensatory mechanism that can influence results in clinical trials of DKD.

Association between non-registration of chronic kidney disease and mortality and cardiovascular outcome: a time-to-event analysis of retrospective primary care data

ObjectivePatients with impaired kidney function and increased albuminuria are at risk of developing cardiovascular disease (CVD). Previous research has revealed that a substantial proportion of patients with chronic kidney disease...

Elevated urinary angiotensinogen excretion links central and renal hemodynamic alterations

Inappropriate activation of intrarenal renin–angiotensin system (RAS) may contribute to the pathogenesis of cardio-renal syndrome (CRS). We aimed to examine the cross-sectional associations of urinary angiotensinogen (AGT) excretion, a biomarker of intrarenal RAS activity, with central (aortic) and renal hemodynamic parameters in middle-aged and older adults, including patients with chronic kidney disease. Aortic and renal hemodynamic parameters were measured using applanation tonometry and duplex ultrasonography in 282 participants. Urinary AGT, liver-type fatty acid-binding protein (L-FABP), and plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were measured for each participant. Multiple linear regression analyses demonstrated that urinary AGT levels were associated with aortic blood pressures, pulsatile measures of renal blood flow, plasma NT-proBNP and urinary L-FABP levels after adjusting for potential covariates, including age, sex, body mass index, estimated glomerular filtration rate (GFR), and medication use. Additionally, when classified based on GFR stages and urinary AGT levels, plasma NT-proBNP and urinary L-FABP levels increased in participants with lower GFR and higher AGT groups. Our findings suggest that urinary AGT excretion is a shared determinant of central (aortic) and renal hemodynamics in middle-aged and older adults, providing clinical evidence for the potential role of intrarenal RAS activity in the development of CRS.

Race-free estimated glomerular filtration rate equation in kidney transplant recipients: development and validation study

ObjectiveTo compare the performance of a newly developed race-free kidney recipient specific glomerular filtration rate (GFR) equation with the three current main equations for measuring GFR in kidney transplant recipients.DesignDevelopment...

Radical cystectomy and urinary diversion outcomes in patients with single vs. double renal unit: A 2:1 matched-pair analysis.

To evaluate perioperative and functional outcomes of radical cystectomy (RC) and urinary diversion (UD) in patients with a single kidney (SK) vs. double kidneys (DK). We reviewed records of patients who underwent RC for bladder cancer with a history of prior or concurrent nephrectomy at USC between 2004 and 2020. Patients with chronic kidney disease who were already on dialysis were excluded. UD, perioperative complications, and postoperative glomerular filtration rate (GFR) of the SK group were compared with a group of patients who underwent RC with DK using 2:1 matching with respect to age, sex, preop GFR, and tumor stage. We included 186 patients (SK = 62 and DK = 124). Half of the SK patients underwent continent UD. SK patients had a higher length of hospital stay compared to the DK group; however, 90-day complications, readmission, and mortality rates were similar. In patients with continent diversion, SK vs. DK showed similar 90-day complications (71% vs. 69%, P = 1.0). SK patients had significantly lower GFRs at discharge, 3-, and 12-month following RC compared to the DK group. Postoperative GFRs of the SK patients with continent vs. incontinent UD were statistically similar. On multivariable analysis, UD (i.e. continent vs. incontinent) was not associated with post-op GFR decline at discharge, 3- and 12-month following RC. Perioperative outcomes of radical cystectomy patients with single kidney are similar to double kidney patients, except for more GFR decline in single kidney cases. Continent urinary diversion in single kidney is as safe as double kidney patients.

Elevated checkpoint inhibitor expression and Treg cell number in autosomal dominant polycystic kidney disease and their correlation with disease parameters and hypertension.

Autosomal dominant polycystic kidney disease (ADPKD) has cancer-like pathophysiology. In this study, we aimed to investigate the phenotype of peripheral blood (PB) T cell subsets and immune checkpoint inhibitor expression of ADPKD patients across different chronic kidney disease (CKD) stages. Seventy-two patients with ADPKD and twenty-three healthy controls were included in the study. The patients were grouped into five different CKD stages, according to glomerular filtration rate (GFR). PB mononuclear cells were isolated and T cell subsets and cytokine production were examined by flow cytometry. CRP levels, height-adjusted total kidney volume (htTKV), rate of hypertension (HT) differed significantly across different GFR stages in ADPKD. T cell phenotyping revealed significantly elevated CD3+ T cells, CD4+, CD8+, double-negative, and double-positive subsets and significantly elevated IFN-γ and TNF-α producing subsets of CD4+, CD8+ cells. The expression of checkpoint inhibitors CTLA-4, PD-1, and TIGIT by T cell subsets was also increased to various extent. Additionally, Treg cell numbers and suppressive markers CTLA-4, PD-1, and TIGIT were significantly elevated in ADPKD patients' PB. Treg CTLA4 expression and CD4CD8DP T cell frequency in patients with HT were significantly higher. Lastly, HT and increased htTKV and higher frequency of PD1+ CD8SP were found to be risk factors for rapid disease progression. Our data provide the first detailed analyses of checkpoint inhibitor expression by PB T cell subsets during stages of ADPKD, and that a higher frequency of PD1+ CD8SP cells is associated with rapid disease progression.

Retrospective Analysis of Hospitalized Patients with Type 2 Diabetes Mellitus Treated with Glucagon-Like Peptide 1 Receptor Agonist Therapy.

The use and overall benefit of glucagon-like peptide-1 (GLP-1) receptor agonist therapy for hospitalized patients with type 2 diabetes mellitus (DM) with chronic kidney disease (CKD) has limited data regarding impact and safety. We studied the impact and safety of GLP-1 receptor agonist therapy in hospitalized DM patients with CKD. Retrospective study of 51 patients using either dulaglutide (n = 3) or liraglutide (n = 48). Glomerular filtration rate (GFR) groups of stages 3 to 5 and 1 and 2 were compared. The primary outcome was total amount of insulin within the last 24 hours in the hospital. The secondary outcomes were glucose management and safety. Mean insulin total amount within the last 24 hours in the hospital significantly differed (P = 0.01) between the GFR groups, with the GFR stages 3 to 5 group (mean 0.5, standard deviation 0.36) having a lower mean insulin level than the GFR stages 1 and 2 group (mean 0.8, standard deviation 0.45). Point-of-care glucose reached the target of 140 to 180 mg/dL within the last 24 hours in hospital, with increased odds for the GFR stages 3 to 5 group as compared with the GFR stages 1 and 2 group (odds ratio 4.08, 95% confidence interval 1.05-15.83, P = 0.04). For both GFR groups, there were minimal adverse events. Almost all of them continued GLP-1 receptor agonist therapy at discharge (94.1%). The use of GLP-1 receptor agonist therapy had better outcomes in patients with GFR stages 3 to 5 as compared with GFR stages 1 and 2. There were minimal adverse events reported for both GFR groups. This study suggests that the off-label use of GLP-1 receptor agonists for hospitalized DM patients with CKD may be useful.

PS-P10-2: NON-LINEAR RELATIONSHIP BETWEEN CKD PROGRESSION AND SYSTOLIC AND DIASTOLIC BLOOD PRESSURE; IKI EPIDEMIOLOGICAL STUDY OF ATHEROSCLEROSIS AND CKD (ISSA-CKD)

Objectives: The aim of the study is to assess the non-linear relationship between systolic and diastolic blood pressure and chronic kidney disease (CKD) progression. Design and Method: This is a cohort study using annual health check-up data from 2008 to 2018 in Iki City, Nagasaki, Japan. After excluding those who had health check-ups only once or those with the missing value for serum creatinine or urinalysis, a total of 5919 participants were included in the present analysis. The outcome of the present analysis was CKD progression, which was defined as worsening either the glomerular filtration rate stage or albumin creatinine ratio stage according to KDIGO classification at a visit and at the end of follow-up. Non-linear effects of SBP and DBP on the progression of CKD were evaluated by Cox proportional analysis with a restricted cubic spline controlling for confounding factors. Results: During a mean follow-up of 4.9 years, 1167(19.7%) CKD progression was observed. As each SBP and DBP were classified into quartiles, there was a linear relationship between SBP and CKD progression (p < 0.001 for trend), on the other hand, there was no linear relationship between DBP and CKD progression (p = 0.534 for trend). For restricted cubic spline, we found a sigmoid curve-like relationship between SBP and CKD progression, in which CKD progression increased in accord with BP increase. For DBP, we found a U-like shape relationship between DBP and CKD progression, in which there was the lowest risk at nearly 70–80 mmHg, and then the risk for CKD progression increased to both lower and higher DBP. Conclusions: The findings of the present analysis showed a near-linear trend that higher SBP had a significant relationship with an increase in CKD progression. On the other hand, the relationship between DBP and CKD progression was not linear, and both lower and higher DBP could be related to CKD progression.

Daily behavioral and sleep patterns are associated with aging-induced male-specific disorders in individuals with reduced renal function

The development of aging-induced male-specific disorders is accelerated by impaired renal function. Although aging-induced male-specific disorders are clinically serious complications in individuals with reduced renal function, their practical management strategies remain obscure. The purpose of this cross-sectional study was to investigate the association between daily behavioral and sleep patterns and aging-induced male-specific disorders in individuals with reduced renal function. Eighty men with glomerular filtration rate stage 2-4 (age, 67±9years), sedentary behavior and physical activity were assessed using a triaxial accelerometer. The mean sleep time was calculated from the sleep time during the accelerometer measurement. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). Aging-induced male-specific disorders were assessed using the Aging Males' Symptoms Questionnaire (AMS). A lower moderate to vigorous-intensity physical activity (MVPA) time and a higher PSQI score were independently associated with a higher AMS score. Moreover, when the participants were divided into four groups according to the median MVPA values and the PSQI score (more or less than 6 points), the AMS score was the highest in those with a lower MVPA time and a higher PSQI score. In the mediation analysis, the PSQI score did not mediate a correlation between the MVPA time and AMS score. MVPA time also did not mediate a correlation between the PSQI and AMS scores. Collectively, these findings suggest that increasing MVPA time and improving sleep quality may contribute to attenuating aging-induced male-specific disorders in individuals with reduced renal function.

MP25-02 RADICAL CYSTECTOMY AND URINARY DIVERSION OUTCOMES IN PATIENTS WITH SINGLE VS. DOUBLE KIDNEY: A 2:1 MATCHED-PAIR ANALYSIS

You have accessJournal of UrologyCME1 May 2022MP25-02 RADICAL CYSTECTOMY AND URINARY DIVERSION OUTCOMES IN PATIENTS WITH SINGLE VS. DOUBLE KIDNEY: A 2:1 MATCHED-PAIR ANALYSIS Alireza Ghoreifi, Richard Mora, Sanam Ladi-Seyedian, Farshad Sheybaee Moghaddam, Jie Cai, Gus Miranda, Monish Aron, Anne Schuckman, Mihir Desai, Inderbir Gill, Siamak Daneshmand, and Hooman Djaladat Alireza GhoreifiAlireza Ghoreifi More articles by this author , Richard MoraRichard Mora More articles by this author , Sanam Ladi-SeyedianSanam Ladi-Seyedian More articles by this author , Farshad Sheybaee MoghaddamFarshad Sheybaee Moghaddam More articles by this author , Jie CaiJie Cai More articles by this author , Gus MirandaGus Miranda More articles by this author , Monish AronMonish Aron More articles by this author , Anne SchuckmanAnne Schuckman More articles by this author , Mihir DesaiMihir Desai More articles by this author , Inderbir GillInderbir Gill More articles by this author , Siamak DaneshmandSiamak Daneshmand More articles by this author , and Hooman DjaladatHooman Djaladat More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002568.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Limited data is available regarding the outcomes of patients with single kidney (SK) who undergo radical cystectomy (RC) and urinary diversion (UD). The aim of this study is to evaluate perioperative and functional outcomes of SK patients with bladder cancer (BC) who undergo RC. METHODS: We reviewed the records of patients who underwent RC for BC with history of prior or concurrent nephrectomy due to non-functional kidney, renal cancer, or upper tract urothelial carcinoma (UTUC) between 2004 and 2020. Patients with chronic kidney disease who were already on dialysis were excluded. UD, perioperative complications, and postoperative glomerular filtration rate (GFR) of the SK group were compared with a group of patients who underwent RC with double kidneys (DK) using 2:1 matching with respect to age, sex, preop GFR, and tumor stage. RESULTS: A total of 186 patients (SK=62 and DK=124) were included. Baseline features of these two groups were similar (Table 1-A). Half of the SK patients underwent continent UD. SK patients had a higher length of hospital stay compared to the DK group; however, 90-day complications, readmission, and mortality rates were similar (Table 1-B). In patients with continent diversion, SK vs. DK showed similar 90-day complications, including metabolic acidosis and dehydration (71% vs. 69%, p=1.0). In terms of GFR changes, SK group showed significantly lower GFRs at discharge as well as 3- and 12-months following RC compared to the DK group (Figure 1-A). Nevertheless, no significant difference was observed in postoperative GFRs of the SK patients with continent vs. incontinent UD (Figure 2-B). On multivariable analysis, UD (i.e., continent vs. incontinent) was not associated with post-op GFR decline at discharge, 3- and 12-months following RC. CONCLUSIONS: Perioperative outcomes of single kidney patients undergoing radical cystectomy are similar to double kidney patients, except for more GFR decline in single kidney cases. Continent urinary diversion in single kidney patients is as safe as double kidney cases. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e427 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Alireza Ghoreifi More articles by this author Richard Mora More articles by this author Sanam Ladi-Seyedian More articles by this author Farshad Sheybaee Moghaddam More articles by this author Jie Cai More articles by this author Gus Miranda More articles by this author Monish Aron More articles by this author Anne Schuckman More articles by this author Mihir Desai More articles by this author Inderbir Gill More articles by this author Siamak Daneshmand More articles by this author Hooman Djaladat More articles by this author Expand All Advertisement PDF DownloadLoading ...

Особливості перебігу діабетичної хвороби нирок у хворих на латентний автоімунний діабет дорослих

Актуальність. Латентний автоімунний діабет дорослих (LADA) є гетерогенним типом цукрового діабету (ЦД), що поєднує ознаки цукрового діабету 1-го (ЦД1) та 2-го типу (ЦД2). Дані щодо частоти і структури мікросудинних ускладнень при LADA малочисельні й доволі суперечливі, практично відсутня інформація про особливості їх перебігу, що вказує на необхідність проведення досліджень у цьому напрямку. Мета дослідження: з’ясувати особливості перебігу діабетичної хвороби нирок у хворих на латентний автоімунний діабет дорослих порівняно з класичними типами цукрового діабету. Матеріали та методи. Обстежено 112 хворих на ЦД із діабетичною хворобою нирок (ДХН). Пацієнтів розподілили на три групи: І— 54 особи з LADA, ІІ— 30 хворих на ЦД1, ІІІ— 28 пацієнтів із ЦД2. Особливості перебігу ДХН вивчали на підставі оцінки даних анамнезу, клінічного обстеження, значень швидкості клубочкової фільтрації (ШКФ), альбумінурії, відношення альбуміну до креатиніну в сечі. Результати. За даними анамнезу діагноз ДХН у пацієнтів із LADA встановлювався в середньому через 3 роки після маніфестації ЦД, при цьому на 4,5 року раніше, ніж при ЦД1, але на 1,3 року пізніше, ніж при ЦД2. Аналіз показників ШКФ показав, що при LADА найбільш часто (у 63% пацієнтів) реєструвалась категорія G3 (G3а— у 46%, G3b— у 17% пацієнтів). Решта обстежених мали категорію G1 (7%), G2 (24%), і тільки в 6% пацієнтів виявлено стадію G4. У пацієнтів усіх груп переважали категорії альбумінурії А1 та А2 (при LADА— по 43% осіб у кожній категорії), водночас категорія A3 при LADA реєструвалась удвічі частіше, ніж при ЦД1. При LADA переважаючими фенотипами ДХН були неальбумінурійне порушення функції нирок (НАПН) (43%) і альбумінурійний фенотип (АФ) (35%), при ЦД1— АФ (50%) і НАПН (40%), а при ЦД2 усі три фенотипи реєструвалися майже з однаковою частотою (АФ— у 32%, НАПН— у 29% пацієнтів, прогресуюче зниження функції нирок — у 39% хворих). Висновки. Перебіг діабетичної хвороби нирок в осіб із латентним автоімунним діабетом дорослих відрізняється від такого при класичних типах цукрового діабету, що вказує на необхідність розробки специфічного алгоритму ведення цієї категорії пацієнтів.

Usefulness of presepsin / creatinine ratio as a new index that corrects for renal function.

Background : Presepsin (P-SEP) is a highly specific sepsis marker, and its fluctuation with respect to advanced renal impairment or sample agitation has not been fully investigated. We evaluated several renal function-corrected P-SEP indices to establish a simple index and its reference range. Methods : Blood samples for P-SEP measurement were collected with minimal agitation. P-SEP levels were measured using the rapid automated immunoanalyzer "PATHFAST." This study included 85 chronic kidney disease (CKD) patients, 65 healthy volunteers, and 4 sepsis patients. Results : Patients stratified by estimated glomerular filtration rate (GFR) had significantly higher P-SEP levels for CKD stage G3, especially the advanced GFR stage. We evaluated presepsin / creatinine (P-SEP / CRE) and P-SEP / eGFR ratios as possible indices for renal function. The P-SEP / CRE ratio exhibited no increase correlating with the GFR stage and was identical in the normal and CKD groups ; P-SEP / eGFR decreased if GFR stage worsened. The P-SEP / CRE ratio became significantly higher in sepsis patients and was a more useful index with a reference range of 67-263. Conclusions : P-SEP levels were inversely correlated with renal function, indicating the necessity to consider the influence of renal impairment in CKD patients. The P-SEP / CRE ratio is helpful for sepsis diagnosis, even in patients with renal impairment. J. Med. Invest. 68 : 105-111, February, 2021.

Measured glomerular filtration rate (GFR) significantly and rapidly decreases after radical cystectomy for bladder cancer

Precise determination of glomerular filtration rate (GFR) is essential for the management of patients with muscle-invasive bladder cancer (MIBC). We aim to describe the early evolution of measured GFR (mGFR) after radical cystectomy and urinary diversion (RCUD) and to identify risk factors for GFR decline. GFR measurement using 51Cr-EDTA continuous infusion, estimated GFR (eGFR) from five published equations and renal scintigraphy with split renal function determination were performed before and 6 months after RCUD. Chronic Kidney Disease (mGFR < 60 mL/min/1.73 m2) and GFR stages were defined according to the KDIGO guidelines using mGFR. Twenty-seven patients (men 85%, median age 65, IQR 59; 68 years) were included. A total of 20 (74%) patients experienced significant mGFR decline at 6 months postoperatively. Median mGFR decreased from 84.1 pre-operatively (IQR 65.3; 97.2) to 69.9 mL/min/1.73 m2 (IQR 55.0; 77.9) 6 months after surgery (p < 0.001). Thirteen (48%) patients had a progression to a worse GFR stage. Of the 22 patients without pre-operative CKD, 5 (23%) developed post-operative CKD. Diabetes mellitus was more frequent in patients in the highest tertile of relative mGFR decline (44% vs. 11%, p = 0.02) and platinum-based adjuvant chemotherapy tended to be more frequently used in these patients (44% vs. 17%, p = 0.06). Importantly, pre-operative weight was independently and negatively associated with post-operative mGFR and with mGFR slope in multivariable analyses. In this prospective series, we demonstrated that early and significant mGFR decline occurred after RCUD and perioperative platinum-based chemotherapy, especially in patients with diabetes mellitus and overweight.

Dyslipidemia in pediatric CKD patients: results from KNOW-PedCKD (KoreaN cohort study for Outcomes in patients With Pediatric CKD).

Pediatric as well as adult patients with chronic kidney disease (CKD) are susceptible to cardiovascular disease (CVD) events, which increase their mortality. Dyslipidemia is thought to be one of the most important contributing risk factors for developing CVD. This study aimed to evaluate the prevalence of dyslipidemia and assess clinical and laboratory risk factors associated with dyslipidemia in East Asian pediatric patients with CKD. From April 2011 to April 2016, 469 patients with CKD aged < 20years were enrolled in KNOW-PedCKD (the KoreaN cohort study for Outcomes in patients With Pediatric Chronic Kidney Disease); 356 patients were included in the final analysis. Using the baseline data of the cohort cross-sectionally, a multivariable logistic regression analysis was performed to assess the risk factors for dyslipidemia; a subanalysis for each lipid abnormality was also done. The prevalence of dyslipidemia was 61.5% (n = 219). For dyslipidemia, nephrotic range proteinuria and 25-hydroxyvitamin D deficiency significantly increased the adjusted odds ratio. In the subanalysis, glomerulonephropathy as the origin of CKD and nephrotic range proteinuria significantly increased the risks for high total cholesterol and high low-density lipoprotein cholesterol. Overweight or obese body mass index z-score, elevated proteinuria, hypocalcemia, and 1,25-dihydroxyvitamin D deficiency were significantly associated with low high-density lipoprotein cholesterol. Glomerular filtration rate stage 3b or higher and hyperphosphatemia significantly increased the risk for high triglycerides. Long-term data accumulation and prospective analysis are needed to clarify the relationship between CKD progression and dyslipidemia and to find additional risk factors for dyslipidemia.

EVALUATION OF CARBAPENEM USE AMONG PATIENTS AT INTENSIVE CARE UNIT (ICU) IN SANA'A, YEMEN

Drug Utilization Evaluation (DUE) studies are designed to evaluate and improve the rational use of medications. In this study, DUE has focused on drugs used in high risk patients such as critically ill cases. Carbapenems are beta-lactam type antibiotics with broad-spectrum of activity which cover gram-positive, gram-negative and anaerobic bacteria. The heavy use of carbapenems (imipenem or meropenm) could increase the risk of multi-drug resistant (MDR) pathogens. This study was a prospective and cross sectional study performed at intensive care unit (ICU) of Al-Matwakel hospital in Sana'a, Yemen. The study was conducted from September 2018 to March 2019. All of the patients were on imipenem or meropenem as an empiric treatment or based upon microbiology culture results included in the study. Total of 80 patients at ICU were evaluated. The results of the study showed that empiric therapy was in most cases (91.25%; P&lt; 0.001).In addition; about 36.3% of the patients required dosage adjustment according to glomerular filtration rate (GFR) stages. Also according to GFR calculation, 43.8% of the patients were in stage 3. In the present study, the frequency of therapeutic duplication of ceftriaxone with carbapenem was reported in 38 patients. The major drug-drug interactions were observed with tramadol-imipenem, tramadol-meropenem, and amlodipine-simvastatin. The result of the study showed that empiric therapy was unjustified in most cases (91.25%). In addition, about 36.3% of the patients required dosage adjustment according to GFR stages. According to GFR calculation, 43.8% of the patients were in stage 3. In the present study, the frequency of therapeutic duplication and drug-drug interactions were observed.&#x0D; Peer Review History: &#x0D; UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main purpose of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency.&#x0D; Received file &#x0D; &#x0D; Average Peer review marks at initial stage: 4.5/10&#x0D; Average Peer review marks at publication stage: 8.0/10&#x0D; Reviewer(s) detail:&#x0D; Name: Dr. (Mrs) Amaka Mgbahurike&#x0D; Affiliation: University of Port Harcourt, Nigeria&#x0D; E-mail: amaka_mgbahurike@yahoo.com&#x0D; &#x0D; Name: Dr. Mahmoud S. Abdallah&#x0D; Affiliation: University of Sadat city, Egypt&#x0D; E-mail: dr_samy777@yahoo.com&#x0D; Comments of reviewer(s): &#x0D;

Clinical evaluation of presepsin considering renal function.

Presepsin, a glycoprotein produced during bacterial phagocytosis, is used as a sepsis marker for bacterial infections. However, presepsin levels are affected by renal function, and the evaluation criteria according to kidney function or in chronic kidney diseases remain controversial. Furthermore, presepsin may be increased by sample stirring, but no studies have evaluated this effect.In this study, we excluded the effect of stirring by standardizing the blood collection conditions, analyzed the influence of kidney function on presepsin concentrations, and recalculated the reference range based on the findings. EDTA-whole blood from 47 healthy subjects and 85 patients with chronic kidney disease was collected to measure presepsin by PATHFAST. Presepsin was found to be significantly correlated with the levels of creatinine (r = 0.834), eGFRcreat (r = 0.837), cystatin-C (r = 0.845), and eGFRcys (r = 0.879). Furthermore, in patients with CKD, presepsin levels stratified by eGFRcys showed a significant increase in the CKD G2 patient group and with advancing glomerular filtration rate stage. The following values were obtained: Normal: 97.6 ± 27.4 pg/mL, CKD G1: 100.2 ± 27.6 pg/mL, CKD G2: 129.7 ± 40.7 pg/mL, CKD G3: 208.1 ± 70.2 pg/mL, CKD G4: 320.2 ± 170.1 pg/mL, CKD G5: 712.8 ± 336.3 pg/mL. The reference range, calculated by a nonparametric method using 67 cases of healthy volunteers and patients with chronic kidney disease G1, was found to be 59–153 pg/mL, which was notably lower than the standard reference range currently used. Presepsin concentrations were positively correlated with a few biomarkers of renal function, indicating the necessity to consider the effect of renal function in patients with renal impairment. Using the recalculated reference range considering kidney function may improve the accuracy of evaluating presepsin for diagnosis of sepsis compared to the standard reference currently in use.

Medical costs associated with chronic kidney disease progression in an Asian population with type 2 diabetes mellitus

We aim to examine difference in incremental direct medical costs between non-progressive and progressive chronic kidney disease (CKD) in type 2 diabetes mellitus (T2DM) in Singapore. This was a prospective study on 676 patients with T2DM attending a diabetes centre in a regional hospital. Annual direct medical costs were extracted from the administrative database. Ordinary least squares regression was used to estimate contribution of CKD progression to annual costs, adjusting for demographics and baseline clinical covariates. Over mean follow-up period of 2.8 ± 0.4 years, 266 (39.3%) had CKD progression. The excess total follow-up medical costs from baseline was S$4243 higher in progressors compared to non-progressors (P = 0.002). The mean cost differential between the two groups increased from S$2799 in Stages G1-G2 to S$11180 in Stage G4. Inpatient cost accounted for 63.4% of total cost of progression. When stratified by glomerular filtration rate stages, the respective total mean annual costs at stages glomerular filtration rate Stages G3a-G3b and G4 were S$3290 (132%; P = 0.001) and S$4416 (135%; P = 0.011) higher post-progression. Chronic kidney disease progression in T2DM is associated with high medical costs. The cost of progression is higher with higher severity of CKD stage at baseline and could be largely driven by inpatient admission.

Macrophages in diabetic nephropathy in patients with type 2 diabetes.

Inflammation plays a role in the development of diabetic nephropathy (DN) in type 2 diabetes. Although macrophages have been found in experimental models of DN, little is known regarding the presence of macrophages in patients with DN. Therefore, we investigated the presence and phenotype of glomerular and interstitial macrophages in relation to clinical and histopathological parameters in patients with DN. Renal autopsy samples were obtained from 88 type 2 diabetic patients with histologically proven DN and stained for CD68 and CD163 as general and M2/anti-inflammatory markers of macrophages. Renal damage was scored based on histopathological classification of DN. Control renal autopsy samples were obtained from patients without renal abnormalities and from diabetic patients without DN. Positive cells per glomerulus were counted. Interstitial macrophages were counted semi-quantitatively. Macrophages were present in all groups. In the DN group, the mean number of CD68+ cells per glomerulus and CD163+ cells per glomerulus was 4.2 (range 0-19) and 2.1 (range 0-14.47), respectively. The distribution was similar between all histopathological classes. Glomerular CD163+ macrophages were positively associated with DN class, interstitial fibrosis and tubular atrophy, and glomerulosclerosis. Interstitial CD68+ macrophages were correlated with glomerular filtration rate stage and albuminuria. Our results demonstrate that macrophages are present in the glomeruli and interstitium of type 2 diabetic patients with DN and of controls. Although patients and controls had similar numbers of glomerular macrophages, glomerular anti-inflammatory CD163+ macrophages were associated with pathological lesions in DN. Taken together with the correlation between interstitial macrophages and interstitial fibrosis and tubular atrophy, DN class, and renal function, this finding suggests that macrophages may play a role in DN progression. Therefore, targeting macrophages may be a promising new therapy for inhibiting the progression of DN.

Japanese society for dialysis therapy clinical guideline for "hemodialysis initiation for maintenance hemodialysis".

Yuzo Watanabe, Kunihiro Yamagata, Shinichi Nishi, Hideki Hirakata, Norio Hanafusa, Chie Saito, Motoshi Hattori, Noritomo Itami, Yasuhiro Komatsu, Yoshindo Kawaguchi, Kazuhiko Tsuruya, Yoshiharu Tsubakihara, Kazuyuki Suzuki, Ken Sakai, Hideki Kawanishi, Daijo Inaguma, Hiroyasu Yamamoto, Yoshiaki Takemoto, Noriko Mori, Kazuyoshi Okada, Hiroshi Hataya, Takashi Akiba, Kunitoshi Iseki, Tadashi Tomo, Ikuto Masakane, Tadao Akizawa, and Jun Minakuchi, for “Hemodialysis Initiation for Maintenance Hemodialysis” Guideline Working Group, Japanese Society for Dialysis Therapy

Associated factors of different combined albuminuria and estimated glomerular filtration rate stages among patients with type 2 diabetes mellitus

Albuminuria and reduced glomerular filtration rate have a great impact on the progression of end-stage renal disease and cardiovascular events. The purpose of the study was to determine the clinical factors associated with different combined albuminuria and glomerular filtration rate among patients with type 2 diabetes. A total of 361 consecutive outpatients who attended the department of endocrinology and metabolism were retrospectively recruited in this cross-sectional study. Urinary albuminuria-creatinine ratio and estimated glomerular filtration rate were applied to designate different renal stages. Polytomous logistic regression was then performed to assess the associated clinical factors among these different renal stages. The proportion of subjects with normoalbuminuria with low glomerular filtration rate was 8.3 % in all study patients. We demonstrated that associated factors of different combined albuminuria and estimated glomerular filtration rate stages were quite distinct, and correlate factors for normoalbuminuria with low glomerular filtration rate were older age (p < 0.001), longer duration of diabetes (p = 0.009), and more statin/fibrate use (odd ratio [95 % confidence interval]: 4.37 [1.45–13.18]; p = 0.009). The associated factors among different combined albuminuria and estimated glomerular filtration rate stages were distinct. Whether early modification of these related factors can prevent or delay the progression of kidney disease warrants further investigations.