Diet In Renal Disease Formula Research Articles

Urinary neutrophil gelatinase-associated lipocalin as a clinical biomarker in patients with diabetic nephropathy in Beni-Suef Governorate, Egypt

Aim To demonstrate the importance of the marker of tubulointerstitial damage, urinary neutrophil gelatinase-associated lipocalin (uNGAL), in the follow-up of the progression of chronic kidney disease in patients with type 2 diabetes mellitus. Patients and methods A total of 60 patients with type 2 diabetes mellitus with various degrees of renal impairment were subdivided into three categories based on urine albumin/creatinine ratio (UACR): 20 patients with normoalbuminuria ( 300 mg albumin/g Cr). Few exclusion criteria were considered such as infections, neoplasia, and any inflammation that could interfere with uNGAL measurement. Twenty healthy individuals were taken as a control group. Serum creatinine, UACR, urine protein, and estimated glomerular filtration rate (eGFR) are measured to determine their correlation with uNGAL, which was measured using a suitable human NGAL ELISA kit. The Modification of Diet in Renal Disease formula was used to calculate the eGFR in patients. Results The differences between the means of uNGAL in the different patients’ groups were found to be highly statistically significant (P Conclusion NGAL may be useful as a clinical marker to predict and assess the progression of diabetic nephropathy in patients with type 2 diabetes mellitus with nephropathy.

Kidney disease screening in a group of female health personnel: Who are often missing?

Background and Objective: Data on early-stage of chronic kidney disease (CKD) and the prevalence of CKD are very limited, especially more scanty in our female population. Hence, data from a kidney screening program organized at the Chattagram Maa-O-Shishu Hospital premises in connection with the observance of World Kidney Day 2018 were looked at for renal function among a group of female health personnel. Methods: This was a cross-sectional study among a group of female health personnel working at the hospital. Age, body weight, height, Body mass index (BMI), and blood pressure were documented, and serum creatinine was measured at a single sitting. The kidney function was estimated by calculating the glomerular filtration rate (GFR) using the Modified Diet in Renal Disease formula. Kidney function was classified according to estimated GFR (eGFR) and Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines. Results: A total of 101 female health personnel were studied – physicians - 23; nurses - 45, and health assistants - 33. Majority participants (51%) were in the age group of 20–29 years; 5% were 90 mL/min category. An inverse relation between the age and eGFR and a direct relation between the BMI and eGFR were observed in the study. Conclusion: The results indicate that low GFR levels and consequently a high burden of likely CKD are prevailing in our female population. It is not clear whether such observations are the result of the transportability problems associated with the GFR prediction equations or with the suitability of K/DOQI guidelines for the classification of CKD in our population or both. Well-planned, larger, and community- and hospital-based studies are warranted to clarify these issues, especially for our female population.

Erythropoietin Level and Percentage of Urinary Albumin Are Important for Renal Recovery in Patients with Multiple Myeloma Receiving Novel Agents

BackgroundRenal impairment (RI) is one of the most common complications of multiple myeloma (MM), and is a major cause of morbidity and mortality. Monoclonal free light chain (FLC) is associated with most RI in patients with MM, and previous reports showed that early reduction of FLC is associated with renal recovery. Novel agents including bortezomib and immunomodulatory drugs (IMiDs) contribute to early reduction of FLC, leading to renal recovery. However, some patients developed irreversible RI despite the use of novel agents, and the factors that predict renal recovery other than early reduction of FLC remain unclear. This study retrospectively analyzed the clinical variables that affect renal recovery in patients with RI receiving novel agents.Patients and MethodsThe study population consisted of 235 consecutive patients with newly diagnosed MM (NDMM) between January 2008 and April 2018 at Kameda Medical Center, Japan. All patients were treated with bortezomib or IMiD-based combined chemotherapy in the frontline setting. Nine patients who received less than 2 courses of chemotherapy were excluded because it was difficult to assess renal recovery. RI was defined as an estimated pretreatment glomerular filtration rate (eGFR) of <50 ml/min/1.73 m2. We used the simplified Modification of Diet in Renal Disease formula to calculate eGFR. Maximum renal response was evaluated according to International Myeloma Working Group (IMWG) renal response criteria. Major renal response was defined as achieving PRrenal and CRrenal. Erythropoietin (EPO) was measured, if a patient had anemia (male: hemoglobin [Hb] <12.0 g/dl, female Hb <11.0 g/dl). Statistical analyses were performed with EZR, which is a graphical user interface for R ver. 3.2.2.Ethical considerationsThis study was approved by the institutional review board of Kameda Medical Center and conducted in accordance with the principles of the Declaration of Helsinki.ResultsThe median patient age was 72.2 years and the median observation period was 40.8 months. Moderate-to-severe RI (eGFR <50 mL/min/1.73 m2) was identified in 104 patients (46.5%). The median eGFR was 27.9 ml/min/1.73 m2. The percentage of patients with light-chain only isotype was 28.8%, and 57.7% of the patients had kappa light chain. According to IMWG renal response criteria, 54.8% of patients achieved major renal response, including PRrenal 4.8% and CRrenal 49.0%. Baseline involved FLC, reduction of FLC, light chain-only isotype, and kappa light chain type were not statistically significant between patients with or without major renal response. There were significant differences in age, calcium, EPO, and percentage of urinary albumin excretion between responders and non-responders (Table). Receiver operating characteristic curve analysis showed that the best cutoff values were 24.6 mIU/ml for EPO and 24.7% for the percentage of urinary albumin (Figure). The factors associated with major renal response included age <75 years, calcium, percentage of urinary albumin <25%, and EPO ≥25 mIU/ml. The multivariate logistic regression analysis showed that age <75 years [Odds ratio (OR)=9.86; p=0.005], calcium (OR=8.94; p=0.010), percentage of urinary albumin <25% (OR=15.5; p=0.002), and EPO ≥25 mIU/ml (OR=18.4; p<0.001) were independent predictive factors for renal recovery. When patients were divided based on the percentage of urinary albumin <25% and level of EPO ≥25 mIU/ml, the proportion of those who achieved major renal recovery was significantly different among 3 groups (both urinary albumin <25% and EPO ≥25 mIU/ml vs. either urinary albumin <25% or EPO ≥25 mIU/ml vs. neither urinary albumin <25% nor EPO ≥25 mIU/ml: 84.2% vs 32.3% vs. 6.0%, p<0.001).ConclusionOur results indicate that early reduction of FLC could have less predictive value for renal recovery compared to that in previous reports because early FLC reduction could be obtained in almost all patients irrespective of improvement in renal function. However, the level of serum EPO and the percentage of urinary albumin emerged as positive predictive factors for renal recovery in patients with RI receiving novel agents. The combination of these 2 variables could predict renal recovery more precisely. DisclosuresNo relevant conflicts of interest to declare.

Transient acute kidney injury after cardiac surgery does not independently affect postoperative outcomes.

The objective of this study was to assess the incidence of in-hospital acute kidney injury (AKI) after cardiac surgery by comparing preoperative baseline renal function with renal function during the postoperative period and at discharge, and to relate these indices with in-hospital postoperative outcomes. A retrospective analysis was performed over a 4-year period from a series of 426 adult patients. Kidney function was based on serum creatinine (SCr), Cockroft-Gault estimated creatinine clearance (eCrCl), and glomerular filtration rate estimated with the Modification of Diet in Renal Disease formula (eGFR). Baseline values were compared with "peak" values of altered kidney function postoperatively, and "discharge" values. In-hospital mortality and complication rates were compared between patients with transient and persistent AKI, and those without postoperative AKI. After surgery, AKI (Risk-Injury-Failure-Loss-Endstage [RIFLE] classes Injury and Failure) was diagnosed in 14.6-17.5% of patients based on peak values. AKI diagnosis was reduced to 3.6-4.5% when SCr, eCrCl, and eGFR were measured at discharge. In-hospital mortality of patients with transient AKI was 4% versus 26% in patients with AKI at discharge (odds ratio = 0.11, 95% confidence interval 0.02-0.62, P = 0.011). A diagnosis of AKI based on measurements of eGFR during the postoperative period was nearly four times more frequent than the same diagnosis at discharge. Transient AKI was the predominate presentation of postoperative kidney dysfunction in this study. Transient AKI did not affect in-hospital outcomes compared with patients without AKI. Patients with persistent AKI at discharge had the highest mortality.

Quantification of NGAL in Urine of Endurance Cycling Athletes.

Neutrophil gelatinase-associated lipocalin (NGAL) is a glycoprotein released during early phases of a postischemic kidney in response to kidney injury, inflammation, and oxidative stress. It can be detected in urine after 2 hours of an ischemic event. The aim was to measure and to correlate the level of urine NGAL (uNGAL) with urea, creatinine, and glomerular filtration rate (GFR) of endurance cycling athletes (n = 19) and physically active individuals (control, n = 17). Quantification of urea and creatinine were performed by dry chemical method, and GFR was calculated using the modification of diet in renal disease formula, according to Brazilian Society of Nephrology. uNGAL analyses were performed by enzyme linked immunoabsorbent assay. Analyses were performed 48 hours after exercises. uNGAL (in ng/mL) levels, expressed as median, minimum, and maximum, in cyclist group, 387.7 (109.7-1691.0), was significantly higher than that observed in control (physically active) group, 141.5 (4.8-657.0), (P < .05). No significant correlations were observed between uNGAL and creatinine, urea, or GFR (P > .05). Results have pointed to increased uNGAL levels in endurance cycling athletes. Increase of uNGAL in absence of clinical signs or alterations in creatinine, urea, or GFR might suggest that there is metabolic adaptation to endurance exercise, or possibly predisposition to acute kidney injury over time.

Plasma marinobufagenin immunoreactivity in patients with chronic kidney disease: a case control study.

Experimental data have shown increased plasma levels of marinobufagenin in kidney failure. In this case-controlled retrospective analysis, we evaluated plasma marinobufagenin immunoreactivity in hemodialysis patients compared with subjects with normal kidney function. Sixty-eight adult hemodialysis patients with chronic kidney disease (34 females and 34 males) as well as 68 age-, gender-, and blood pressure-matched subjects without chronic kidney disease were enrolled. Patients on stable hemodialysis regimen for at least 3 mo before the study were included. Exclusion criteria were: age <18 yr, severe liver or heart insufficiency, and overhydration. Subjects without chronic kidney disease must have had an estimated glomerular filtration rate ≥60 ml·min-1·1.72 m-2 according to the Modification of Diet in Renal Disease formula. Plasma marinobufagenin immunoreactivity was significantly ( P < 0.001) higher in hemodialysis patients (1.66 ± 1.13 nmol/l) compared with subjects with normal kidney function (0.46 ± 0.23). In hemodialysis patients, plasma marinobufagenin immunoreactivity was higher in men compared with women. A significant positive correlation has been found between plasma marinobufagenin immunoreactivity and serum NT-proBNP, NT-proANP, or aldosterone concentrations in all analyzed subjects. In hemodialyzed patients with plasma marinobufagenin immunoreactivity above median value 5-yr, all-cause mortality was higher compared with those with plasma marinobufagenin concentration below median. We have shown that plasma marinobufagenin immunoreactivity is increased in patients with end-stage kidney failure treated with hemodialysis parallel to the increase in serum NT-proBNP, NT-proANP, and aldosterone concentrations. Higher marinobufagenin immunoreactivity has been associated with worse survival in hemodialyzed patients.

Serum uric acid and arterial hypertension—Data from Sephar III survey

ObjectivesThis paper aims to evaluate the association between serum uric acid (SUA) levels, arterial hypertension (HT) prevalence, blood pressure values control, kidney function and intima media thickness (IMT), as a surrogate marker of early atherosclerosis, in a representative group of Romanian adult population.Materials and methodsThe study sample consists in 1920 adults included in SEPHAR III (Study for the Evaluation of Prevalence of Hypertension and cArdiovascular Risk in Romania) survey (mean age 48.63 years, 52.76% females) collecting data for SUA levels, blood pressure (BP) measurements, kidney function by estimated glomerular filtration rate (eGFR) and carotid IMT. SUA levels between 2,40–5,70mg/dl in females and 3,40–7,00mg/dl in males respectively were considered normal. HT and HT control were defined according to the current guidelines. IMT evaluation was assessed by B-mode Doppler ultrasound evaluation.ResultsHypertensive subjects had significantly higher values of SUA compared with normotensive subjects, hypertensive patients were 1.713 times more likely to have higher values of SUA. Among treated hypertensive patients, those without optimal BP control had significantly higher SUA levels compared with those with optimal BP control, the presence of hyperuricemia increasing the odds of suboptimal BP control by 1.023. Hyperuricemic subjects had significantly lower eGFR values compared with normouricemic ones, on an average with 14.28ml/min/1.73m2 by Modification of Diet in Renal Disease formula (MDRD) and with 16.64ml/min/1.73m2 by Chronic Kidney Disease Epidemiology Collaboration formula (CKD-EPI), with an indirect association between SUA levels and eGFR values (rs = -0.319 / -0.347), independent of age. IMT values recorded in hyperuricemic subjects were significantly increased, on an average with 0.08mm, compared with normouricemic subjects, with a direct association between SUA levels and IMT values (rs = 0.263), independent of BP values.ConclusionThe results of our study offers support that increased SUA levels are associated with arterial hypertension and with suboptimal BP control in treated hypertensive subjects. The decline in kidney function, independent of age, and also increased IMT values as a marker of atherosclerosis, were also correlated with elevated SUA values. Hyperuricemia screening may have a role in identifying patients at risk of developing HT and lowering SUA levels may improve not only BP control in treated HT patients but also decrease total cardiovascular mortality by slowing the progression of atherosclerosis and renal failure in hypertensive patients.

Cystic fibrosis related diabetes before lung transplantation impacts survival but not long-term renal function

Introduction Lung transplantation (LT) is the final therapeutic option for cystic fibrosis (CF) patients with end stage lung disease. Lung transplanted CF patients differ from other LT patients because of their younger age, better survival after LT, but also specific associated comorbidities related to their underlying disease, particularly CF related diabetes (CFRD). The objective was to describe the prevalence of CFRD before and after LT; and to analyse survival and renal function after LT according to CFRD status before LT. Methods CF patients treated in the Lyon CF reference centre and transplanted at the Lyon University Hospital (France) between 2004 and 2014 were retrospectively included. Genotype (classified in delF508 homozygous, delF508 heterozygous or other), pancreatic status, age at LT and survival were recorded. The following criteria were recorded three months before LT, between three and six months after LT, and at each year of follow-up until December 2016: glucose tolerance status (CFRD or others), daily insulin dose requirement; renal function, defined by the estimated glomerular filtration rate (GFR, calculated with the Modification of Diet in Renal Disease formula); and daily glucocorticoid (GC) dose. Analysis for repeated measures data was conducted by using linear mixed-effect regression models that included fixed and random effects. Results Sixty-three adult CF patients were transplanted. Thirty-two (53.3%) patients were delF508 homozygous. All were pancreatic insufficient, and 42 (70%) had CFRD before LT. The mean ± SD calculated GFR before LT was 109 ± 47 mL/min/1.73 m2, and did not differ according to CFRD status (P = 0.68). The mean ± SD age at LT was 27.6 ± 8.4 year. The median (IQR) time of follow-up was 5.6 (3.8–8.2) years and 12 (20%) patients died in the follow-up: three patients died in the first three post-operative months, seven patients in the five years following LT and the last two respectively at 6 and 8 years after the LT. The prevalence of CFRD was 68% (41/60) and 54% (20/37) respectively at two and five years after LT. For the 27 patients who had persistent insulin-treated CFRD, insulin requirement decreased with an estimated slope of −2.1 ± 2.9 IU/day per year (P Conclusions CFRD before LT was associated with a poor survival after LT in CF patients, which should conduct to a better management of diabetes control in the peri- and post-operative period after LT. Some patients with pre-LT CFRD get free of diabetes after LT. CFRD is not associated with renal insufficiency after LT. Others factors might participate to renal insufficiency after LT such as perioperative hemodynamic conditions and immunosuppressive drugs.

Lixisenatide and Renal Outcomes in Patients with Type 2 Diabetes—A Post-Hoc Analysis of the ELIXA Trial

Limited data exist on long-term effects of GLP-1 receptor agonists on kidney function and albuminuria in T2D. In ELIXA, a study of cardiovascular safety of lixisenatide (Lixi) over a median follow-up of 25 months in 6068 patients (pts) with T2D and an acute coronary event ≥180 days before screening, slower progression of urinary albumin-to-creatinine ratio (UACR) was seen with Lixi vs. placebo (Pbo). In a mixed-effect model with repeated measures for comparisons between treatment (Tx) groups of changes in UACR, the interaction between Tx and baseline (BL) UACR categories was significant (p&amp;lt;0.01). We assessed change in estimated glomerular filtration rate (eGFR, per the 4-variable modification of diet in renal disease formula) and UACR by BL albuminuria status. eGFR was not significantly different for Lixi vs. Pbo overall or by BL albuminuria status. UACR percent change from BL was lower for Lixi vs. Pbo in pts with micro- or macroalbuminuria (Table). In a Cox proportional hazards model adjusted for BL and on-trial HbA1c, Lixi was associated with 23% lower risk for first macroalbuminuria event in pts without BL macroalbuminuria (HR 0.77; 95% CI: 0.62, 0.96; p=0.0174). In conclusion, in pts with T2D and a recent acute coronary event, Lixi reduced UACR progression in pts with BL micro- or macroalbuminuria and was associated with lower incidence of macroalbuminuria beyond glycemic control. Disclosure M.A. Muskiet: Consultant; Self; Eli Lilly and Company, Novo Nordisk A/S. L. Tonneijck: Consultant; Spouse/Partner; Eli Lilly and Company. Y. Huang: Consultant; Self; Sanofi. M. Liu: Employee; Self; Sanofi. A. Saremi: Employee; Self; Sanofi US. H.L. Heerspink: Consultant; Self; AbbVie Inc., AstraZeneca. Advisory Panel; Self; Boehringer Ingelheim GmbH. Consultant; Self; Janssen Research &amp; Development, Fresenius SE &amp; Co. KGaA. Advisory Panel; Self; Merck &amp; Co., Inc.. Consultant; Self; Mitsubishi Tanabe Pharma Corporation. D.H. van Raalte: Advisory Panel; Self; Sanofi. Research Support; Self; Sanofi, Boehringer Ingelheim GmbH. Advisory Panel; Self; Boehringer Ingelheim GmbH, Merck &amp; Co., Inc., Novo Nordisk Inc.. Research Support; Self; AstraZeneca.

Long-term Follow-up of Living Kidney Donors With Chronic Kidney Disease at 1 Year After Nephrectomy

BackgroundAlthough renal function recovery of living kidney donors has been reported in a number of studies, many patients show poor recovery, and the long-term prognosis of these patients has not been well studied. In this investigation we explored the long-term prognosis of renal function in patients with chronic kidney disease (CKD) at 1 year after nephrectomy. MethodsPatients who underwent donor nephrectomy during the period from March 2006 to April 2014, with a follow-up creatinine study at 1 year postoperatively and more than 3 years of follow-up, were included in the study. Creatinine and estimated glomerular filtration rate (eGFR, using the Modification of Diet in Renal Disease formula) before and after surgery were studied. Age, sex, history of hypertension or diabetes, body mass index, blood pressure, complete blood count, preoperative routine serum chemistry, and urine study results were reviewed. ResultsAmong 841 patients who had donor nephrectomy, 362 were included in the study. There were 111 patients (30.6%) with eGFR <60 mL/min/1.73 m2 at 1 year postsurgery, and the median follow-up period was 62.8 months (interquartile range [IQR] 42.0–86.3 months). The maximum eGFR after 3-year follow-up was studied, and 48 patients (43.2%) never recovered eGFR to >60 mL/min/1.73 m2. Age, history of hypertension, preoperative eGFR, and eGFR at 1 year were predictive factors at univariate analysis. Multivariate analysis of these factors was studied, and age (52.5 [IQR 47–55.7] vs 47 [IQR 7–53] years, odds ratio [OR] 1.1, 95% confidence interval [CI] 1.02–1.15, P = .007), history of hypertension (16.7% vs 1.6%, OR 10.0, 95% CI 1.09–92.49, P = .042), and eGFR at 1 year (53.9 [IQR 50.3–56.0] vs 57.0 [IQR 54.2–58.4] mL/min/1.73 m2, OR 0.8, 95% CI 0.72–0.92, P = .002) remained as significant risk factors. ConclusionOf all living donors, 15.7% had CKD after >3 years of follow-up. Close observation is warranted when donors have CKD after 1 year follow-up, as 43.2% fail to recover renal function. Patients who are older, have a history of hypertension, and have low eGFR at 1-year follow-up are especially at risk.

Impact of Sofosbuvir-Based Regimens for the Treatment of Hepatitis C After Liver Transplant on Renal Function: Results of a Canadian National Retrospective Study.

We assessed the impact of sofosbuvir-based regimens on renal function in liver transplant recipients with recurrent hepatitis C virus and the role of renal function on the efficacy and safety of these regimens. In an expanded pan-Canadian cohort, 180 liver transplant recipients were treated with sofosbuvir-based regimens for hepatitis C virus recurrence from January 2014 to May 2015. Mean age was 58 ± 6.85 years, and 50% had F3/4 fibrosis. Patients were stratified into 4 groups based on baseline estimated glomerular filtration rate (calculated by the Modification of Diet in Renal Disease formula): < 30, 30 to 45, 46 to 60, and > 60 mL/min/173 m2. The primary outcome was posttreatment changes in renal function from baseline. Secondary outcomes included sustained virologic response at 12 weeks posttreatment and anemia-related and serious adverse events. Posttreatment renal function was improved in most patients (58%). Renal function declined in 22% of patients, which was more marked in those with estimated glomerular filtration rate < 30 mL/min/173 m2, advanced cirrhosis (P = .05), and aggressive hepatitis C virus/fibrosing cholestatic hepatitis (P < .05). High rates (80%-88%) of sustained virologic response at 12 weeks posttreatment were seen across all renal function strata. Cirrhotic patients with glomerular filtration rates < 30 mL/min/173 m2 had sustained virologic response rates at 12 weeks posttreatment comparable to the overall patient group. Rates of anemia-related adverse events and transfusion requirements increased across decreasing estimated glomerular filtration rate groups, with notably more occurrences with ribavirin-based regimens. Sofosbuvir-based regimens improved overall renal function in liver transplant recipients, with sustained virologic response, suggesting an association of subclinical hepatitis C virus-related renal disease. Sustained virologic response rates at 12 weeks posttreatment (80%-88%) were comparable regardless of baseline renal function but lower in cirrhosis.

Complement-fixing donor-specific anti-HLA antibodies and kidney allograft failure

Detection of donor-specific antibodies (DSA) has improved the risk classification and post-transplant evaluation of kidney recipients. Moreover, assessment of DSA C1q-binding ability has been shown to improve the individual risk classification of transplant patients for allograft loss, especially when detected after transplantation. The aim of this study was to evaluate the additional clinical impact of C1q-binding DSA detection in a population that was extensively monitored for DSA and MFI alterations. Forty-two kidney allograft recipients were followed-up at multiple time points for up to 5 years after transplantation for the presence of anti-HLA DSA-IgG total. The samples that were positive for these antibodies were retrospectively tested for the presence of complement-binding antibodies. Overall, 24 patients presented DSA, 29% (7) of which also produced complement-binding DSA. Compared to patients with non-C1q-binding DSA and non-sensitized patients, patients with C1q-binding DSA after transplantation had the lowest allograft survival rate at 5 years (p = 0.042) and showed a lower estimated glomerular filtration rate (based on the Modification of Diet in Renal Disease formula) during the post-transplant follow-up period (p = 0.01). Thus, post-transplant monitoring for complement-binding DSA is a useful tool for predicting individuals most at risk for allograft failure, and might also be beneficial for evaluation of immunosuppression regimens.

Does Histopathology of Implanted Kidney According to Banff 07 Help Predict Long-term Transplantation Outcome?

Analyses of peritransplant biopsies of deceased-donor kidneys show high incidence of chronic abnormalities. The question arises whether chronic abnormalities present at implantation determine engrafted kidney fate regardless of other concomitant variables.The aim of this study was to identify risk factors of graft loss considering histopathological changes present at implantation scored according to Banff 07 criteria. Patients and methodsInclusion criteria (n = 300) was engraftment between years 2000 and 2008 and availability of implantation biopsy. Analyzed abnormalities present in donor biopsy were arteriolar hyalinization, interstitial fibrosis, intimal sclerotization, tubular atrophy, total inflammation, and percentage of sclerotic glomeruli (Banff classification).Allograft function was estimated by abbreviated Modification of Diet in Renal Disease formula and proteinuria semi-quantitatively by standard dip-stick test. Kaplan-Meier estimate was used to assess graft survival. Searching for independent risk factors of graft survival was performed by means of Cox proportional hazards models (SAS System, SAS Institute Inc, Cary, NC, United States). ResultsIn one-factor analyses, predictors of kidney allograft loss were donor age, donor history of diabetes, kidney allograft dysfunction within first posttransplant year, and recipient chronic hepatitis C. In terms of chronic abnormalities, arteriolar hyalinization of any intensity nearly doubled the risk of allograft loss.Independent risk factors of kidney allograft loss in multivariate analysis were donor age, posttransplant diabetes mellitus, proteinuria after engraftment, and recipient hepatitis C. ConclusionThe effect of arteriolar hyalinization on renal transplant survival is probably interwoven with other predictors of graft loss. Recognizing the negative impact of recipient chronic hepatitis C on graft survival, hepatitis C virus treatment should be provided to patients with advanced chronic kidney disease, patients on wait lists, or patients already transplanted.

Kallistatin Concentration and Hypertension in Heart Transplant Recipients

Development of arterial hypertension is to some extent related to decreased activity of the kallikrein-kinin system. This poorly understood hormonal system consists of blood proteins playing a role in the process of inflammation, coagulation, blood pressure control, and pain conduction. The system consists of kallikreins (plasma and tissue), kallistatin, kininogens, kinins (bradykinin, kallidin-lizynobradykinin), kininases (I and II), and membrane receptors of bradykinin. The aim of the study was the assessment of kallistatin in correlation to blood pressure value in heart transplant recipients. Patients and MethodsKallistatin level was estimated in 131 heart transplant recipients on standard 3 drugs immunosuppressive regimens (calcineurin inhibitor, mycophenolate mofetil/mycophenolic acid, and steroids) in correlation to inflammation markers and blood pressure values. Additionally, 22 healthy volunteers served as controls. In cross-sectional study, kallistatin and catecholamine concentrations were assessed using commercially available assays. ResultsKallistatin concentration did not differ significantly among heart transplant recipients in comparison with controls; serum noradrenaline concentration was lower in the study group. In the orthotopic heart transplant group, kallistatin correlated with renal function; estimated glomerular filtration rate was calculated by Modification of Diet in Renal Disease formula (r = −0.28, P < .01; hemoglobin r = −0.19, P < .05; cholesterol level r = −0.23, P < .01; low-density lipoprotein r = 0.25, P < .01; ferritin r = 0.21, P < .05; noradrenaline r = −0.28, P < .01). No correlation with blood pressure values were revealed. In multivariate analysis, cholesterol serum level and age predicted 32% of variability of kallistatin concentration. ConclusionKallistatin among heart transplant recipients does not seem to be the pathogenetic factor of arterial hypertension but may be involved in the development of hyperlipidemia often present in this group of patients.

474 - High Calculated Glomerular Filtration Rate is Associated with Treatment-Related Mortality in Older Adults Undergoing Allogeneic Hematopoietic Cell Transplantation

Background: Older adults are undergoing allogeneic hematopoietic cell transplant (allo-HCT) at historically unprecedented rates. However, identifying older adults at high risk for adverse outcomes remains a challenge. Hypothesis: High calculated glomerular filtration rate (GFR) at the time of transplant admission (TxA) is a surrogate marker for low muscle mass and predicts treatment-related mortality (TRM). Methods: All patients age 65 who underwent allo-HCT at Washington University School of Medicine between October 2012 and June 2017 were retrospectively screened for inclusion. Patients with previous allo-HCT, HLA mismatched unrelated donors and donor-specific antibodies were excluded. GFR was calculated using the Modified of Diet in Renal Disease formula. Patients were stratified into four groups: Low (GFR < 60), Intermediate (60-90), High (90-120) and Very High (>120). The primary outcome was the cumulative incidence of TRM, which was defined as any death prior to day +28 and any death following day +28 without relapse. Relapse was treated as a competing risk. The secondary outcome was overall survival (OS). Results: 127 patients were identified. Median follow up was 6.4 and 15.2 months in all patients and surviving patients, respectively. 23, 68, 29 and 7 patients were in the Low, Intermediate, High and Very High GFR groups at TxA. GFR group was not associated with any baseline demographic or clinical characteristic with the exception of KarnofksyPerformance Score (KPS) (P = .02) (Table 1). TRM at 2 years was significantly different between Low (38%, 95% C.I. 16%-59%), Intermediate (31%, 95% C.I. 19%-43%), High (48%, 95% C.I. 27%-70%) and Very High (71%, 95% C.I. 28%-100%) GFR groups (P = .02) (Figure 1). Similarly, OS was significantly different among the groups (P = .02). On pairwise analysis, Very High GFR was associated with inferior survival compared to all other groups (all P < .01). High GFR was associated with inferior survival compared to Intermediate GFR (P = .046). After adjusting for KPS, Very High GFR continued to be associated with inferior OS (aHR: 4.58, 95% C.I. 1.9-10.9) compared to Intermediate GFR.Table 1Demographics and Clinical Characteristics.GFR CategoryLowIntermediateHighVery HighTotal2368297Age*68 (65-75)68 (65-75)68 (65-76)67 (65-73)Male Gender13 (57)43 (63)20 (69)3 (43)Caucasian22 (96)64 (94)28 (97)7 (100)HCT CI 02 (9)9 (13)3 (10)0 (0) 1 to 25 (22)12 (18)6 (21)3 (43) ≥316 (70)47 (69)20 (69)4 (57)KPS < 9011 (48)31 (46)21 (72)6 (86)*Median (range). Open table in a new tab *Median (range). Conclusion: High GFR was associated with inferior outcomes following allo-HCT. Consequently, GFR at TxA may provide novel information to identify older adults at high risk for TRM during allo-HCT. Larger studies are needed to evaluate this association and prospective studies are needed to evaluate possible interventions to decrease TRM in at-risk patients.

Glomerular filtration rate calculated by modification of diet in renal disease formula can be an indicator of impaired glucose tolerance and diabetes in coronary artery disease

Background: There is an increased risk for coronary artery disease (CAD) at modestly elevated levels of blood glucose which is still below the present threshold for type 2 diabetes mellitus (T2DM). In the present study, we aimed to define impaired glucose tolerance (IGT) and T2DM in patients with stable CAD and observe the relationship between clinical and laboratory findings. Materials and Methods: A total of 132 patients who had stable CAD and who had not been diagnosed as glucose intolerance or diabetes were enrolled. In one of the groups, there were patients with IGT or T2DM results and the other one consisted of patients with normal oral glucose tolerance test (OGTT) results. The Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) was investigated in patients with fasting plasma glucose (FPG) <100 mg/dl. Results: The prevalance of IGT and T2DM was 30.3%. In IGT + T2DM group, waist/hip ratio and creatinin level were significantly higher and estimated glomerular filtration rate (eGFR) was low. Only eGFR calculated by Modification of Diet in Renal Disease (MDRD) formula was a reliable parameter. MDRD eGFR ≤70 ml/dk/m2 independently predicted IGT + T2DM diagnosis with 50% sensitivity but with 82% specificity. Although it is insufficient to use it as an optimal screening test because of lower sensitivity, it can be a reliable indicator of IGT + DM in patients who had eGFR ≤70. Insulin resistance was diagnosed in 29% of patients whose pretest values were FPG <100 mg/dl. Conclusion: MDRD eGFR can be an indicator for IGT + T2DM. OGTT irrespective of FPG level should be used to determine the presence of IGT + T2DM in stable CAD.

Safety and Efficacy of Induction Therapy With Thymoglobulin in AB0-Incompatible Kidney Transplantation

IntroductionData suggest an additional role of T cells in antibody-mediated rejections. In 2001 a protocol for AB0-incompatible kidney transplantation based on B-cell–depleting anti–CD20 antibody rituximab, antigen-specific blood group IgG immunoadsorption, intravenous immunoglobulins, and triple immunosuppression was introduced in Europe, which used induction therapy with the use of interleukin-2 receptor antibody (IL2-RA) basiliximab. We used thymoglobulin in AB0-incompatible patients as induction in the face of high immunologic risk. MethodsWe retrospectively evaluated a cohort of 9 AB0i living donation (LD) recipients from 2011 to 2014. Desensitization included blood group–specific immunoadsorption. Eighteen AB0-compatible LD recipients receiving induction therapy with thymoglobulin served as control subjects. Another control group consisted of 18 AB0-compatible LD recipients receiving basiliximab. Follow-up was 24 months. We captured graft function by estimating glomerular filtration rate (eGFR by Modification of Diet in Renal Disease formula), rejection episodes, and bacterial and viral infections. ResultsAll patients experienced immediate graft function. No significant or clinical differences were observed regarding graft function, rejection rates, or infections between the groups, although there seemed to be slightly higher cytomegalovirus infection rates due to preemptive therapy strategy. ConclusionsThymoglobulin appears to be similar in safety and efficacy to IL-2-antagonists in AB0i kidney transplantation.

Anaemia, renal dysfunction and in-hospital outcomes in patients with heart failure in Botswana.

Anaemia and renal dysfunction are associated with an increased morbidity and mortality in heart failure (HF) patients. To estimate the frequency and impact of anaemia and renal dysfunction on in-hospital outcomes in patients with HF. A total of 193 consecutive patients with HF admitted to Princess Marina Hospital, Gaborone, Botswana, from February 2014 to February 2015, were studied. Anaemia was defined as haemoglobin &lt;13 g/dL for men and &lt;12 g/dL for women. Renal dysfunction was defined by an estimated glomerular filtration rate (eGFR) &lt;60 mL/min/1.73 m2, calculated by the simplified Modification of Diet in Renal Disease formula. The in-hospital outcomes included length of hospital stay and mortality. The mean (standard deviation (SD)) age was 54.2 (17.1) years and 53.9% of the patients were men. The overall median eGFR was 75.9 mL/min/1.73 m2 and renal dysfunction was detected in 60 (31.1%) patients. Renal dysfunction was associated with hypertension (p=0.01), diabetes mellitus (p=0.01) and a lower haemoglobin level (p=0.008). The mean (SD) haemoglobin was 12.0 (3.0) g/dL and 54.9% of the patients were anaemic. Microcytic, normocytic and macrocytic anaemia were found in 32.1%, 57.5% and 10.4% of patients, respectively. The mean (SD) haemoglobin level for males was significantly higher than for females (12.4 (3.3) g/dL v. 11.5 (2.5) g/dL; p=0.038). Anaemia was more common in patients with diabetes (p=0.028) and in those with increased left ventricular ejection fraction (p=0.005). Neither renal dysfunction nor anaemia was significantly associated with the length of hospital stay or in-hospital mortality. Anaemia and renal dysfunction are prevalent in HF patients, but neither was an independent predictor of length of stay or in-hospital mortality in this population. These findings indicate that HF data in developed countries may not apply to countries in sub-Saharan Africa, and call for more studies to be done in this region.

Ledipasvir and tenofovir drug interaction in human immunodeficiency virus-hepatitis C virus coinfected patients: Impact on tenofovir trough concentrations and renal safety.

We evaluate the impact of ledipasvir on both tenofovir plasma trough concentration and estimated glomerular renal function in human immunodeficiency virus-hepatitis C virus coinfected patients receiving a tenofovir-based antiretroviral regimen and treated with ledipasvir/sofosbuvir. Twenty-six patients [81% male, median age: 51 years; hepatitis C virus genotype 1(75%)/4(15%)] were included. Tenofovir trough concentration (interquartile range) increased from 78ngml-1 (53-110) at baseline to 141ngml-1 (72-176) at 1 month (P=0.003). No significant difference on estimated glomerular renal function using both Cockroft-Gault and Modification of Diet in Renal Disease formulae, respectively, [median (interquartile range)] was observed between baseline [101.3mlmin-1 (91.1-114.1); 95.6mlmin-1 (86.5-111.2)], 1 month [102.4mlmin-1 (89.8-112.9), P=0.26; 92.5mlmin-1 (88.1-114.3), P=0.27], end-of-treatment [96.5mlmin-1 (82.4-115.4), P=0.39; 95.4mlmin-1 (84.2-105.4), P=0.16] and 12 weeks after the end of treatment [100.5mlmin-1 (83.3-111.9), P=0.24; 93.4mlmin-1 (82.2-103.5), P=0.16]. Three patients progressed from chronic kidney disease stage 1 to stage 2 at 12 weeks post-treatment. A significant increase in tenofovir exposure through P-glycoprotein inhibition by ledipasvir was confirmed without significant impact on glomerular renal function in our population with normal renal function or mild renal impairment.

Ten-Year Follow-up of Pharmacokinetics-Guided Very Early Cyclosporine Minimization Synchronized With Everolimus Initiation in De Novo Kidney Transplantation

BackgroundMinimization of calcineurin inhibitor (CNI) from the 1st week after kidney transplantation (KT) may reduce the risk of CNI nephrotoxicity. MethodsTen de novo KT recipients who received full exposure cyclosporine (CsA) and prednisolone as initial therapy were enrolled. Initial CsA minimization was 50% and started at day 7 after KT. This was synchronized with everolimus (EVL) initiation. Target trough level of EVL was 3–8 ng/mL. Pharmacokinetics studies of CsA and EVL were studied at week 4. The CsA dosage was further reduced to keep a lowest value of serum creatinine and a target EVL level. Primary outcomes were estimated glomerular filtration rate (eGFR) at baseline and last follow-up. ResultsPatients' mean age at last follow-up was 60.6 ± 11.7 years. Follow-up duration was 121.6 ± 12.8 months. Pharmacokinetics study found that Cmax of CsA ranged from 309 to 1,896 ng/mL, mean area under the receiver operating characteristic curve (AUC) of CsA was 3,449 ± 1,402 ng·h/mL, C0 of EVL was 5.2 ± 1.5 ng/mL, Cmax of EVL was 15.4 ± 4.6 ng/mL, and AUC of EVL was 99.7 ± 26.1 ng·h/mL. Achieved nadir serum creatinine was 1.03 ± 0.33 mg/dL. Achieved best eGFR (Modification of Diet in Renal Disease formula) was 99.7 ± 26 mL/min. eGFR at 12 months was 82 ± 25 mL/min. Last serum creatinine was 1.32 ± 0.45 mg/dL. Last eGFR was 57.2 ± 13.55 mL/min. Actuarial death-censored 10-year graft survival was 100%. Actuarial 10-year patient survival was 80%. ConclusionsOur intervention can lead to an average of 75% CsA minimization and a very good eGFR at 10 years.