Outcome Of End-stage Renal Disease Research Articles

Impact of Socioeconomic Status on Incidence of End-Stage Renal Disease and Mortality After Dialysis in Adults With Diabetes.

To determine whether low socioeconomic status (SES), with or without universal drug coverage, predicts end-stage renal disease (ESRD) and survival after dialysis in patients with diabetes. We conducted a population-based retrospective cohort study in Ontario, Canada. We used ≥65years of age as a surrogate for universal drug coverage. Adults with diabetes were followed from March 31, 1997 to March 31, 2011 for occurrence of the composite primary outcome (acute kidney injury, ESRD requiring dialysis or kidney transplantation). Patients on dialysis with diabetes were followed from April 1, 1994 to March 31, 2011 for occurrence of death or transplantation. SES quintile (Q) was inversely associated with the primary outcome in both age groups; however, the gradient was higher in those <65years of age (Q1:Q5 hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.37-1.49) compared with ≥65years of age (HR, 1.19; 95% CI, 1.15-1.24). Low SES was associated with a lower likelihood of kidney transplantation among those <65years of age (HR, 0.77; 95% CI, 0.65-0.92). In patients on dialysis, low SES was associated with higher mortality (HR, 1.09; 95% CI, 1.02-1.16) in both age groups. This association was eliminated after accounting for the decreased rates of kidney transplantation in lower SES groups. SES is inversely associated with ESRD outcomes in individuals with diabetes, and this disparity is reduced in those ≥65years of age who universally receive prescription drug coverage. Low SES is associated with a higher mortality after dialysis, largely explained by lower kidney transplantation rates in poorer populations.

Blood urea nitrogen is independently associated with renal outcomes in Japanese patients with stage 3\u20135 chronic kidney disease: a prospective observational study

BackgroundBlood urea nitrogen (BUN) is one of the substances that affects the calculated serum osmolality (cSosm). A previous study demonstrated that BUN and cSosm were independently associated with the development of chronic kidney disease (CKD) in patients with preserved kidney function. In advanced CKD stages, there is a concomitant increase in cSosm and BUN levels. However, it remains unclear whether BUN or cSosm levels are related to renal outcomes in patients with moderate to severe kidney dysfunction. The aim of this study was to clarify whether the BUN or cSosm level is associated with kidney disease progression in patients with advanced CKD.MethodsIn this prospective study, we enrolled 459 patients with CKD (stages 3–5). The composite renal endpoint was end-stage renal disease (ESRD) or death, and ESRD alone was added as an alternative outcome. A Cox proportional hazards model was utilized to determine the risk factors for a poor renal outcome. We adjusted for covariates including estimated glomerular filtration rate (eGFR). The cSosm (mOsm/kg) was calculated using the following formula: (2 × sodium) + (BUN/2.8) + (glucose/18).ResultsDuring a median follow-up of 25.8 months, the renal endpoint was observed in 210 patients. Multivariable Cox analysis determined the hazard ratio (HR) [95% confidence interval (CI)] for the composite renal outcome in the second, third, and fourth BUN quartiles were 1.36 (0.72–2.58), 1.87 (0.95–3.66), and 2.66 (1.23–5.76) (P for trend < 0.01), respectively compared with the first BUN quartile. Conversely, by multivariable Cox analysis, the HRs (95% CIs) for poor outcomes in the second, third, and fourth cSosm quartiles, compared with the first cSosm quartile, were 1.13 (0.69–1.87), 0.95 (0.58–1.55), and 1.26 (0.78–2.03), respectively (P for trend = 0.39). In addition, with regard to the renal outcome of ESRD alone, higher BUN quartiles had a significantly increased risk for the outcome, but cSosm levels were not associated with the outcome.ConclusionsHigher BUN levels, but not cSosm levels, were associated with adverse renal outcomes independent of the eGFR, suggesting that BUN may be a useful marker for predicting kidney disease progression.

Contributions of traditional and HIV-related risk factors on non-AIDS-defining cancer, myocardial infarction, and end-stage liver and renal diseases in adults with HIV in the USA and Canada: a collaboration of cohort studies

Adults with HIV have an increased burden of non-AIDS-defining cancers, myocardial infarction, end-stage liver disease, and end-stage renal disease. The objective of this study was to estimate the population attributable fractions (PAFs) of preventable or modifiable HIV-related and traditional risk factors for non-AIDS-defining cancers, myocardial infarction, end-stage liver disease, and end-stage renal disease outcomes. We included participants receiving care in academic and community-based outpatient HIV clinical cohorts in the USA and Canada from Jan 1, 2000, to Dec 31, 2014, who contributed to the North American AIDS Cohort Collaboration on Research and Design and who had validated non-AIDS-defining cancers, myocardial infarction, end-stage liver disease, or end-stage renal disease outcomes. Traditional risk factors were tobacco smoking, hypertension, elevated total cholesterol, type 2 diabetes, renal impairment (stage 4 chronic kidney disease), and hepatitis C virus and hepatitis B virus infections. HIV-related risk factors were low CD4 count (<200 cells per μL), detectable plasma HIV RNA (>400 copies per mL), and history of a clinical AIDS diagnosis. PAFs and 95% CIs were estimated to quantify the proportion of outcomes that could be avoided if the risk factor was prevented. In each of the study populations for the four outcomes (1405 of 61 500 had non-AIDS-defining cancer, 347 of 29 515 had myocardial infarctions, 387 of 35 044 had end-stage liver disease events, and 255 of 35 620 had end-stage renal disease events), about 17% were older than 50 years at study entry, about 50% were non-white, and about 80% were men. Preventing smoking would avoid 24% (95% CI 13-35) of these cancers and 37% (7-66) of the myocardial infarctions. Preventing elevated total cholesterol and hypertension would avoid the greatest proportion of myocardial infarctions: 44% (30-58) for cholesterol and 42% (28-56) for hypertension. For liver disease, the PAF was greatest for hepatitis C infection (33%; 95% CI 17-48). For renal disease, the PAF was greatest for hypertension (39%; 26-51) followed by elevated total cholesterol (22%; 13-31), detectable HIV RNA (19; 9-31), and low CD4 cell count (13%; 4-21). The substantial proportion of non-AIDS-defining cancers, myocardial infarction, end-stage liver disease, and end-stage renal disease outcomes that could be prevented with interventions on traditional risk factors elevates the importance of screening for these risk factors, improving the effectiveness of prevention (or modification) of these risk factors, and creating sustainable care models to implement such interventions during the decades of life of adults living with HIV who are receiving care. National Institutes of Health, US Centers for Disease Control and Prevention, the US Agency for Healthcare Research and Quality, the US Health Resources and Services Administration, the Canadian Institutes of Health Research, the Ontario Ministry of Health and Long Term Care, and the Government of Alberta.

Choice of dialysis modality prior to kidney transplantation: Does it matter?

The population of patients with end stage renal disease (ESRD) is increasing, lengthening waiting lists for kidney transplantation. Majority of the patients are not able to receive a kidney transplant in timely manner even though it is well established that patient survival and quality of life after kidney transplantation is far better when compared to being on dialysis. A large number of patients who desire a kidney transplant ultimately end up needing some form of dialysis therapy. Most of incident ESRD patients choose hemodialysis (HD) over peritoneal dialysis (PD) as the modality of choice in the United States, even though studies have favored PD as a better choice of pre-transplant dialysis modality than HD. PD is largely underutilized in the United States due to variety of reasons. As a part of the decision making process, patients are often educated how the choice regarding modality of dialysis would fit into their life but it is not clear and not usually discussed, how it can affect eventual kidney transplantation in the future. In this article we would like to discuss ESRD demographics and outcomes, modality of dialysis and kidney transplant related events. We have summarized the data comparing PD and HD as the modality of dialysis and its impact on allograft and recipient outcomes after kidney transplantation.

Frailty Predicts an Increased Risk of End-Stage Renal Disease with Risk Competition by Mortality among 165,461 Diabetic Kidney Disease Patients.

To examine the effect of frailty on diabetic kidney disease patients’ risk of progression to end-stage renal disease (ESRD), mortality, and adverse episodes, as whether frailty modifies their risk of developing ESRD and other adverse outcomes remains unclear. We identified 165,461 DKD patients from the Longitudinal Cohort of Diabetes Patients in Taiwan (n=840,000) between 2004 and 2010, classifying them into those without frailty or with 1, 2 and ≥3 frailty components based on a modified version of FRAIL scale. Using Cox proportional hazard regression analysis, we examined the long-term risk of developing ESRD along with their risk of mortality, supplemented by a competing risk analysis against mortality. Among all participants, 66.2% (n=109,586), 27.2% (n=44,986), 5.9% (n=9,799), and 0.7% (n=1090) patients did not have or had 1, 2, and ≥3 frailty components, respectively. After a 4.1-year follow-up, 4.2% patients developed ESRD and 18.5% died. Cox proportional hazard modeling revealed that patients with 1, 2, and ≥3 frailty components had increased risks of developing ESRD (for 1, 2, and ≥3 components, hazard ratio [HR] 1.13, 1.18, and 1.2, respectively) and mortality (HR 1.25, 1.41, and 1.34, respectively), with. 9% and 16% risk elevations for ESRD and mortality per component increase. Competing risk analysis showed that frailty-induced ESRD risk was attenuated partially by mortality in those with moderate frailty. The receipt of palliative care did not attenuate this risk. Frailty increased the risk of ESRD based on a dose-response relationship among DKD patients with risk competition by mortality.

Protein carbamylation in end stage renal disease: is there a mortality effect?

Protein carbamylation is a posttranslational protein modification caused, in part, by exposure to urea's dissociation product cyanate. Additional modulators of protein carbamylation include circulating free amino acid levels, inflammation, diet, smoking, and environmental pollution exposures. Carbamylation reactions can modify protein charge, structure, and function, leading to adverse molecular and cellular responses. These changes have been linked to several pathologic biochemical pathways relevant to patients with end stage renal disease (ESRD) such as accelerated atherosclerosis and dysfunctional erythropoiesis, among others. This review examines the consequences of human protein carbamylation and the clinical impact this is thought to have in patients with ESRD. Recent well-conducted studies across diverse cohorts of patients have independently associated elevations in protein carbamylation to mortality and morbidity in patients with ESRD. Studies are now examining the best strategies to reduce carbamylation load, including interventions aimed at lowering urea levels and restoring amino acid balance. Whether such carbamylation lowering strategies yield clinical improvements remain to be determined. Numerous fundamental studies provide plausible mechanisms for the observed association between protein carbamylation burden and adverse clinical outcomes in ESRD. Studies employing nutritional and dialytic interventions to lower carbamylation may mitigate this risk but the net clinical benefit has not been established.

Association of Angiotensin-Converting Enzyme Inhibitor or Angiotensin Receptor Blocker Use With Outcomes After Acute Kidney Injury

Patients with acute kidney injury (AKI) are at an increased long-term risk of death. Effective strategies that improve long-term outcomes in patients with AKI are unknown. To evaluate whether the use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) after hospital discharge is associated with better outcomes in patients with AKI. This retrospective cohort study used data from the Alberta Kidney Disease Network population database to evaluate 46 253 adults 18 years or older with an episode of AKI during a hospitalization between July 1, 2008, and March 31, 2015, in Alberta, Canada. All patients who survived to hospital discharge were followed up for a minimum of 2 years. Use of an ACEI or ARB within 6 months after hospital discharge. The primary outcome was mortality; secondary outcomes included hospitalization for a renal cause, end-stage renal disease (ESRD), and a composite outcome of ESRD or sustained doubling of serum creatinine concentration. An AKI was defined as a 50% increase between prehospital and peak in-hospital serum creatinine concentrations. Propensity scores were used to construct a matched-pairs cohort of patients who did and did not have a prescription for an ACEI or ARB within 6 months after hospital discharge. The study evaluated 46 253 adults (mean [SD] age, 68.6 [16.4] years; 24 436 [52.8%] male). Within 6 months of discharge, 22 193 (48.0%) of the participants were prescribed an ACEI or ARB. After adjustment for comorbidities, ACEI or ARB use before admission, demographics, baseline kidney function, other factors related to index hospitalization, and prior health care services, ACEI or ARB use was associated with lower mortality in patients with AKI after 2 years (adjusted hazard ratio, 0.85; 95% CI, 0.81-0.89). However, patients who received an ACEI or ARB had a higher risk of hospitalization for a renal cause (adjusted hazard ratio, 1.28; 95% CI, 1.12-1.46). No association was found between ACEI or ARB use and progression to ESRD. Among patients with AKI, ACEI or ARB therapy appeared to be associated with lower mortality but a higher risk of hospitalization for a renal cause. These results suggest a potential benefit of ACEI or ARB use after AKI, but cautious monitoring for renal-specific complications may be warranted.

From arterial stiffness to kidney graft microvasculature: Mortality and graft survival within a cohort of 220 kidney transplant recipients

BackgroundAortic stiffness assessed by carotid-femoral pulse wave velocity (CF-PWV) is a predictor of mortality in several populations. However, little is known in kidney transplant recipients. Our objectives were to evaluate the ability of CF-PWV measured 3 months following transplantation to predict mortality, graft loss and its potential links to measured Glomerular Filtration Rate (mGFR) or kidney graft microvasculature parameters.MethodsThe study is based on a monocentric retrospective cohort including 220 adult kidney graft recipients evaluated three months after transplantation. CF-PWV measures, clinical, laboratory and histological data performed at 3 (M3) and 12 months (M12) following transplantation were retrospectively collected. The two primary endpoints were all-cause mortality and occurrence of end stage renal disease (ESRD) defined by initiation of dialysis.ResultsAfter a median follow up of 5.5 years [1.9; 8.8], death and graft loss occurred in 10 and 12 patients respectively. M3 CF-PWV was an independent mortality risk factor (HR = 1.29 [1.03; 1.61]; p = 0.03), despite no aortic stiffness variation during the first year of transplantation. Of notice, M3 CF-PWV was not associated with M12 mGFR or ESRD outcome. Graft microcirculation assessed by Banff vascular fibrous intimal thickening score (cv) worsened between M3 and M12 (p = 0.01), but no link was found with CF-PWV, mGFR or ESRD outcome. Surprisingly, acute rejections at M3 were associated after adjustment with mortality (p = 0.03) but not ESRD.ConclusionAortic stiffness measured 3 months after kidney transplantation is a strong predictor of mortality with no obvious influence on kidney graft microvasculature or graft loss.

Condition and perspective of renal replacement therapy (RRT) in children in the Republic of Belarus

Objective: to assess the incidence, prevalence and outcomes of end-stage renal disease (ESRD) in children in Belarus, age and gender of patients, etiology of renal diseases leading to ESRD. The study included 121 children, who received RRT as of January 01, 2007 and all subsequent new patients, who started this therapy before December 31, 2016. Results. The incidence of ESRD in children in Belarus aged 0–14 years for the period 2007–2016 was 7 (6; 8) cases per year (4.8 (4.2; 5.2) per million age related population (pmarp)) and at the age of 0–17 years for the period 2009–2016 – 11 (9; 12) cases per year (5.6 (4.8; 6.8) pmarp). The prevalence of ESRD during the period from 2007 to 2016 increased by 31.7% in the group of 0–14 years [from 26 patients (18.3 pmarp) to 38 (24.1 pmarp) patients], and by 46.7% aged 0–17 [from 37 (21 pmarp) to 57 (30.8 pmarp)]. The main cause of ESRD was congenital abnormality of kidneys and urinary tract (44.6% of cases). As of December 31, 2016, 75.4% of children were transplanted, 15.8% received peritoneal dialysis and 8.8% – hemodialysis. 5 year RRT mortality rate was 17.9 deaths per 1000 patient-years and main course of death was infection complications (50%). Conclusions. The incidence of ESRD in children in Belarus corresponds to the average of ESPN/ERA–EDTA Register, the prevalence islower, but with a constant growth. The low mortality rate of patients on RRT and high transplantation activity with insufficient number of preemptive transplantations is maintained.

Plasma biomarkers are associated with renal outcomes in individuals with APOL1 risk variants

G1/G2 variants in the Apolipoprotein L1 (APOL1) gene are associated with end-stage renal disease (ESRD) in people with African ancestry. Plasma biomarkers may have utility for risk stratification in APOL1 high-risk individuals of African ancestry. To evaluate this, we measured tumor necrosis factor receptor 1/2 (TNFR1/2) and kidney injury molecule-1 (KIM1) in baseline plasma specimens from individuals of African ancestry with high-risk APOL1 genotype. Biomarker association with a composite renal outcome of ESRD or 40% sustained decline in estimated glomerular filtration rate (eGFR) was then determined and then assessed as improvement in area under curve. Among the 498 participants, the median age was 56 years, 67.7% were female, and the baseline eGFR was 83.3 ml/min/1.73 m2 with 80 reaching outcome over 5.9 years. TNFR1, TNFR2, and KIM1 at enrollment were independently associated with renal outcome continuously (adjusted hazard ratio 2.0 [95% confidence interval 1.3-3.1]; 1.5 [1.2-1.9]; and 1.6 [1.3-1.9] per doubling in levels, respectively) or by tertiles. The area under the curve significantly improved from 0.75 with the clinical model to 0.79 with the biomarker-enhanced model. The event rate was 40% with all 3 biomarkers elevated (adjusted odds ratio of 5.3 (2.3-12.0) vs. 17% (adjusted odds ratio 1.8 [0.9-3.6] with 1 or 2 elevated and 7% with no biomarkers elevated. Thus, plasma concentrations of TNFR1, TNFR2, and KIM1 are independently associated with renal outcome and improve discrimination or reclassification of African ancestry individuals with a high-risk APOL1 genotype and preserve renal function. Elevation of all markers had higher risk of outcome and can assist with better clinical prediction and improved clinical trial efficiency by enriching event rates.

Telenephrology: Providing Healthcare to Remotely Located Patients with Chronic Kidney Disease

Background: Chronic kidney disease (CKD) patients who live far (>30 miles) from their nephrologist experience lower rates of clinic visit adherence, limited access to treatment, and higher rates of hospitalization and mortality than patients who live in close proximity to their nephrologist. Strategies to minimize disparities between urban and remotely located CKD patients are needed. The purpose of this study was to determine whether adherence to clinic visits and clinical outcomes in the remote management of CKD via telenephrology is comparable to in-person conventional care. Methods: Renal clinic adherence and composite outcomes of death, end-stage renal disease (ESRD), or doubling of serum creatinine (Cr) were measured in geographically remote Hudson Valley VA Medical Center (HVVAMC) CKD patients enrolled in telenephrology (n = 112) and CKD patients enrolled in the Bronx VAMC renal clinic (n = 116). Results: Prior to implementing the telenephrology service, 53.1% of scheduled visits of rural HVVAMC patients to the Bronx VAMC renal clinic were either cancelled or were “no-shows.” This was reduced by nearly half (28.5%) after instituting telenephrology (p < 0.001). Moreover, the frequency of attending appointments was greater in the telenephrology (71.9%) vs. in-person Bronx VA cohort (61.0%). The incidence of the composite outcome of death, ESRD, or doubling of Cr was similar between both groups (p = 0.96) over 2 years of follow-up. Conclusions: Remote CKD care delivered through telenephrology improves renal clinic visit adherence while delivering comparable renal outcomes. Application of this technology is a promising method to provide access to care to rural CKD patients and to minimize the disparity between urban/rural patients.

When is more frequent hemodialysis beneficial?

The use of frequent hemodialysis (HD) is growing, with the hope of improving outcomes in end-stage renal disease. We narratively review the three randomized trials, 15 comparative cohort studies, and several case series of frequent HD that empirically demonstrate the potential efficacy and adverse effects of these regimens. Taken together, the randomized studies suggest frequent HD may result in left ventricular mass regression. This effect is most pronounced when left ventricular mass is abnormal, but attenuated by significant residual urine output. Both frequent short and long HD consistently improved blood pressure control and reduced antihypertensive use, despite greater weekly interdialytic weight gains. Serum phosphate was lowered. Frequent short daytime HD improved health-related quality of life, while frequent long overnight HD did not. Regarding adverse effects, frequent HD patients underwent significantly more procedures to salvage arteriovenous vascular accesses. An absolute increase in hypotensive episodes was observed with frequent short HD, while frequent long HD accelerated residual renal function loss and increased perceived caregiver burden. The effect of frequent HD on mortality is controversial, due to conflicting results and limitations of published studies. Finally, pregnancy outcomes may be substantially better with frequent long HD. On the basis of these data, we suggest frequent HD is most likely to benefit patients with left ventricular hypertrophy particularly if there is minimal urine output, those unable to attain dry weight on a thrice weekly schedule, and pregnant women. All patients receiving frequent HD should be advised of and monitored for potential risks.

Mannose-binding lectin genotypes and outcome in end-stage renal disease: a prospective cohort study.

Patients with end-stage renal disease (ESRD) have high morbidity and mortality rates, with cardiovascular diseases and infections being the major causes of death. Mannose-binding lectin (MBL) has been suggested to play a protective role in this regard. The aim of this study was to investigate a possible clinical association of MBL genotypes (MBL2) with outcome among patients on dialysis or with a functioning graft. A total of 98 patients with ESRD accepted for living-donor renal transplantation or on the waiting list for transplantation were included and prospectively followed for an average of 9 years (range 7.5-9.9). Medical records were evaluated regarding transplantation status, diabetes mellitus, vascular parameters and infections for all the patients. Cox regression models and logistic regression analysis were used for statistical analyses. The cohort was divided into two groups according to the MBL2 genotype (normal A/A versus variant A/O or O/O). We found no evidence for an association between the MBL2 genotype and all-cause mortality, cardiovascular events or bacterial infections (pneumonia, urinary tract infection, fistula infection or other infections). In this cohort, the MBL2 genotype did not seem to be associated with any long-term clinical effects in ESRD patients on dialysis or with a functioning graft.

Patient Outcomes in Renal-Limited Antineutrophil Cytoplasmic Antibody Vasculitis With Inactive Histology

IntroductionLittle is known about the anticipated disease course for individuals who present with renal-limited antineutrophil cytoplasmic antibody (ANCA)−associated vasculitis but who lack inflammation on a kidney biopsy. The impact of immunosuppression on renal and overall survival is unknown.MethodsPatients were recruited from 2005 to 2016 from 8 centers worldwide (N = 16) for this descriptive study. All had positive ANCA, elevated serum creatinine with active urine sediment, histologic evidence of pauci-immune glomerulonephritis without active lesions, and had no evidence of extrarenal vasculitis. We describe the characteristics of this cohort and the differences in the clinical, histologic, and therapeutic parameters of those who developed primary outcomes of end-stage renal disease (ESRD) and vasculitis relapse.ResultsThe cohort was 63% Caucasian, and 75% were men, with a median age of 62 years. At entry, the mean ± SD estimated glomerular filtration rate (eGFR) was 24 ± 20 ml/min per 1.73 m2, and 5 patients required dialysis. Twelve patients received immunosuppressive therapy, 25% experienced disease relapse, and 38% developed ESRD. Patients who developed ESRD had lower baseline eGFRs (8 ± 5 ml/min per 1.73 m2 vs. 35 ± 18 ml/min per 1.73 m2; P = 0.001) and more often required dialysis at presentation (83% vs. 0%; P = 0.001). Patients who relapsed were less likely to receive immunosuppression (25% for the relapsed group vs. 92% for the nonrelapsed group; relative risk: 0.27, risk difference: 67%; P = 0.03).ConclusionAmong these patients, lower initial eGFR and dialysis dependence at presentation might increase the risk for ESRD. Immunosuppression did not affect renal outcomes in this sample of patients but was associated with a reduced risk for vasculitis relapse. More information is needed on factors that predict treatment response in this high-risk group.

Lee West Henderson (1930-2017).

The world of nephrology and dialysis will never be the same with the loss of one of its most distinguished and respected members, Lee W. Henderson, MD, FACP, who passed away on July 3, 2017 at the age of 86. Lee possessed an uncanny understanding of dialysis physiology. His extraordinary contributions in the dialysis field bear testimony to his brilliant mind. The field of dialysis is left with a void that is hard to fill, not only because it has lost an original thinker and an innovative scientist but also a cherished and wonderful human being who was a friend and mentor to many of us. Lee was born in New York in 1930. After finishing at Harvard Medical School (1949–1953) and training at University of Pennsylvania (1953–1961), he came back to Brigham and Women Hospital to work with Dr. John Merrill. He published his first paper on peritoneal dialysis with Dr. Merrill in 1962 1. In 1963, he moved to University of Pennsylvania, where he served for 11 years as Assistant and Associate Professor. During that time, he published his landmark paper in the Journal of Clinical Investigation in collaboration with Dr. Karl Nolph 2. This publication described a kinetic model for mass transport of urea from blood to the peritoneal cavity for the first time. In the same publication, Henderson and Nolph reporterd similarities in the urea and inulin sieving coefficients 2. Around the same time, he also published his remarkable work on convective transport 3. In the late 1960s, Henderson worked with Bluemle to evaluate hemodialyzer functions 4, 5. He reported that the polysulfone membrane was highly permeable and could be designed to provide superior size-selectivity. This subsequently allowed him to test the middle molecule hypothesis. In 1975, Henderson and coworkers published two landmark papers on “convective blood cleansing modality” 4, 6. While working on hemodiafiltration, Henderson also expounded his understanding of the phenomenon of isolated ultrafiltration for the treatment of fluid overload 7. This concept ushered in a new era of volume management in the dialysis world. Both these achievements were revolutionary in concept. In 1975, Henderson joined the University of California at San Diego where he served as professor for 13 years. During that time, in 1983, Lee and his coworkers published the “Interleukin Hypothesis” in the journal, Blood Purification. The interleukin hypothesis described the intradialytic activation of circulating monocytes and the association of a laboratory biocompatibility index with clinical abnormalities 8. Thus was launched another novel era in the field of membrane biocompatibility. In 1989, Lee joined Baxter Healthcare, Chicago, IL, USA as its Vice President. His move to Chicago was largely due to the unique opportunity of getting involved with Baxter's Extramural Grant Program (EGP), which later was called the “Renal Discoveries.” Under the extraordinary leadership of Lee, this became the largest research program in the world dedicated to the prolonging and improving the quality of life for the patients with kidney disease. Through this program, EGP disbursed 25 million dollars on more than 700 projects in more than 20 countries, resulting in over 700 publications with the average impact factor of 4.9. He achieved this huge success at a time when NIH was downsizing its research grants for nephrology. With this tremendous success, Henderson laid the foundation for other extramural research activities such as Baxter Novum, a research center that is focused on improving outcomes in end-stage renal disease. It is a division of the Karolinska Institute in Stockholm, Sweden. The tremendous success of these programs is a testimony to Henderson's leadership and creative qualities besides his invaluable contributions to the world of dialysis 9. After his retirement, he lived in Connecticut and subsequently in Washington. He continued to publish his work even after his retirement. His last scientific paper was published in 2015 10. Currently, over 2 million people are suffering from end-stage renal disease. These patients, their families, their treating physicians and nurses, as well as current researchers in nephrology owe a huge debt to Lee due to his extraordinary accomplishments as a physician as well as a supporter of research. Lee Henderson will be greatly missed by the nephrology communities all over the world.

Safety of Laparoscopic Radical Gastrectomy in Gastric Cancer Patients with End-Stage Renal Disease.

PurposeThe surgical outcomes of end-stage renal disease (ESRD) patients undergoing radical gastrectomy for gastric cancer were inferior compared with those of non-ESRD patients. This study aimed to evaluate the short- and long-term surgical outcomes of ESRD patients undergoing laparoscopic gastrectomy (LG) and open gastrectomy (OG) for gastric cancer.Materials and MethodsBetween 2004 and 2014, 38 patients (OG: 21 patients, LG: 17 patients) with ESRD underwent gastrectomy for gastric cancer. Comparisons were made based on the clinicopathological characteristics, surgical outcomes, and long-term survival rates.ResultsNo significant differences were noted in the clinicopathological characteristics of either group. LG patients had lower estimated blood loss volumes than OG patients (LG vs. OG: 94 vs. 275 mL, P=0.005). The operation time and postoperative hospital stay were similar in both the groups. The postoperative morbidity for LG and OG patients was 41.1% and 33.3%, respectively (P=0.873). No significant difference was observed in the long-term overall survival rates between the 2 groups (5-year overall survival, LG vs. OG: 82.4% vs. 64.7%, P=0.947).ConclusionsIn ESRD patients, LG yielded non-inferior short- and long-term surgical outcomes compared to OG. Laparoscopic procedures might be safely adopted for ESRD patients who can benefit from the advantages of minimally invasive surgery.

End-stage renal disease in children on maintenance dialysis in Benghazi, Libya

Background: End-stage renal disease (ESRD) is a major cause of morbidity and mortality worldwide. Understanding the risk factors of ESRD can help identify preventive strategies and is critical for planning interventions to minimize the disease morbidity and mortality. Objectives: The aim is to identify the demographic and clinical characteristics and risk factors that contribute to ESRD 2005–2016. Settings: The dialysis unit of Benghazi Pediatric Hospital, Benghazi, Libya. Patients and Methods: This is a descriptive case series of all children with ESRD on maintenance dialysis (hemodialysis or peritoneal dialysis) between January 2006 and June 2016. Data were collected from patients' charts and the statistics department of the hospital. Demographic information, the age of onset, duration, and type of dialysis, likely etiology (if documented), complications and comorbidities were all documented and outcome including the cause of death. Results: The mean age of onset of ESRD was 8.5 years; nearly 41% of patients started dialysis at 6–10 years. The majority of patients (72%) resided locally. Male to female ratio was 1.5:1. Consanguinity of parents and family history of renal disease were reported by 12% and 16% of patients, respectively. More than half of patients (51.3%) had had no complications from dialysis. The most common known cause of ESRD was glomerulopathy (18.4%); including glomerulonephritis and nephrotic syndrome. Congenital and hereditary disorders involved 17.1% of cases. These were obstructive uropathy in 9.2% of the patients. The cause was not known in a large proportion (52.6%). Nearly 80% of the patients were alive during the study. Encephlophay (10.5%) and sepsis (6.5%) are the most common causes of death. Conclusions: The clinical profiles, causes, and outcome of ESRD in a specialized center in Benghazi were documented. The study is limited by the high proportion of unknown etiology. Full documentation of underlying etiology is a good clinical practice that should produce better epidemiological studies.

Association between circulating fibroblast growth factor 21 and mortality in end-stage renal disease.

Fibroblast growth factor 21 (FGF21) is an endocrine factor that regulates glucose and lipid metabolism. Circulating FGF21 predicts cardiovascular events and mortality in type 2 diabetes mellitus, including early-stage chronic kidney disease, but its impact on clinical outcomes in end-stage renal disease (ESRD) patients remains unclear. This study enrolled 90 ESRD patients receiving chronic hemodialysis who were categorized into low- and high-FGF21 groups by the median value. We investigated the association between circulating FGF21 levels and the cardiovascular event and mortality during a median follow-up period of 64 months. A Kaplan-Meier analysis showed that the mortality rate was significantly higher in the high-FGF21 group than in the low-FGF21 group (28.3% vs. 9.1%, log-rank, P = 0.034), while the rate of cardiovascular events did not significantly differ between the two groups (30.4% vs. 22.7%, log-rank, P = 0.312). In multivariable Cox models adjusted a high FGF21 level was an independent predictor of all-cause mortality (hazard ratio: 3.98; 95% confidence interval: 1.39–14.27, P = 0.009). Higher circulating FGF21 levels were associated with a high mortality rate, but not cardiovascular events in patient with ESRD, suggesting that circulating FGF21 levels serve as a predictive marker for mortality in these subjects.

Sex differences in vascular dysfunction and cardiovascular outcomes: The cardiac, endothelial function, and arterial stiffness in ESRD (CERES) study.

Recent studies suggest that women with end-stage renal disease (ESRD) may have higher rates of mortality than men, but it is unknown whether sex differences in vascular function explain this disparity. The cardiac, endothelial function, and arterial stiffness in ESRD (CERES) study is an ongoing, prospective observational study designed to investigate vascular function, myocardial injury, and cardiovascular outcomes in ESRD. Among 200 CERES participants (34% women), we evaluated arterial wave reflections as augmentation index normalized to a heart rate of 75 (AIx75), arterial stiffness as pulse wave velocity, and macro- and microvascular endothelial dysfunction as flow-mediated dilation and velocity time integral (VTI). Over a median of 14 months, participants were followed for the composite outcome of cardiovascular hospitalization or all-cause death. Women had higher arterial wave reflection (Mean, SD AIx75 30% ± 9% for women vs. 21% ± 10% for men; P < 0.001) and worse microvascular function (VTI 55 ± 30 cm for women vs. 70 ± 27 cm for men; P = 0.007). After multivariable adjustment, female sex remained associated with a 0.5-SD higher AIx75 (95% CI [0.01, 0.9]) and 0.3-SD lower VTI (95%CI [0.1, 0.7]). Women experienced higher adjusted rates of the composite outcome (HR 2.5; 95%CI [1.1, 5.6]; P = 0.03), and further adjustment for arterial wave reflection attenuated this risk. Vascular dysfunction may partly explain the association of female sex with higher cardiovascular risk and mortality in patients with ESRD. Further studies are needed to explore whether sex differences in vascular function predict long-term outcomes, and whether hormonal or inflammatory factors explain these associations.

Acute kidney injury increases the risk of end-stage renal disease after cardiac surgery in an Asian population: a prospective cohort study

BackgroundAcute kidney injury (AKI) after cardiac surgery is associated with increased morbidity and mortality. The long-term association between AKI and end-stage renal disease (ESRD) in an Asian population is unknown. Given the high prevalence of diabetes and a younger age of presentation for cardiac surgery, it is important to track this progression of kidney disease. Therefore, we studied the long-term risk of ESRD and mortality in our Asian patients who developed AKI after cardiac surgery.MethodsWith ethics approval, we prospectively recruited 3008 patients who underwent cardiac surgery in Singapore between 2008 and 2012, and followed them up till 2014. ESRD and mortality information were obtained from the Singapore Renal Registry and Singapore Registry of Births and Deaths respectively. AKI was defined using the Acute Kidney Injury Network (AKIN) criteria, and ESRD was defined as stage 5 chronic kidney disease requiring renal replacement therapy. The Cox proportional hazards regression model was used to analyze associations between AKI and the primary outcome of ESRD and the secondary outcome of death.ResultsThe AKI incidence was 29.1%. During a mean follow-up of 4.4 ± 2.8 years, 0.9% developed ESRD. The hazard ratio (HR) for developing ESRD was 4.7 (95% C.I. = 1.736–12.603, p = 0.002) for AKIN stage 1 patients, and 5.8 (95% C.I. = 1.769–18.732, p = 0.004) for AKIN stage 2 and 3 patients; while the HR for mortality was 1.7 (95% C.I. = 1.165–2.571, p = 0.007) for AKIN stage 1 patients, and 2.5 (95% C.I. = 1.438–4.229, p < 0.001) for AKIN stage 2 and 3 patients.ConclusionsAKI is associated with ESRD and mortality after cardiac surgery in our Asian population. The trajectory from AKI to ESRD is rapid within 5 years of cardiac surgery. A concerted periodic follow-up assessment is advocated for AKI patients post-cardiac surgery.