Chronic Kidney Disease Epidemiology Research Articles

Effects of Intensive Blood Pressure Lowering on Kidney Tubule Injury in CKD: A Longitudinal Subgroup Analysis in SPRINT

Random assignment to the intensive systolic blood pressure (SBP) arm (<120mmHg) in the Systolic Blood Pressure Intervention Trial (SPRINT) resulted in more rapid declines in estimated glomerular filtration rates (eGFRs) than in the standard arm (SBP<140mmHg). Whether this change reflects hemodynamic effects or accelerated intrinsic kidney damage is unknown. Longitudinal subgroup analysis of clinical trial participants. Random sample of SPRINT participants with prevalent chronic kidney disease (CKD) defined as eGFR<60mL/min/1.73m2 by the CKD-EPI (CKD Epidemiology Collaboration) creatinine-cystatin C equation at baseline. Urine biomarkers of tubule function (β2-microglobulin [B2M], α1-microglobulin [A1M]), and uromodulin), injury (interleukin 18, kidney injury molecule 1, and neutrophil gelatinase-associated lipocalin), inflammation (monocyte chemoattractant protein 1), and repair (human cartilage glycoprotein 40) at baseline, year 1, and year 4. Biomarkers were indexed to urine creatinine concentration and changes between arms were evaluated using mixed-effects linear models and an intention-to-treat approach. 978 SPRINT participants (519 in the intensive and 459 in the standard arm) with prevalent CKD were included. Mean age was 72±9 years and eGFR was 46.1±9.4mL/min/1.73m2 at baseline. Clinical characteristics, eGFR, urinary albumin-creatinine ratio, and all 8 biomarker values were similar across arms at baseline. Compared to the standard arm, eGFR was lower by 2.9 and 3.3mL/min/1.73m2 in the intensive arm at year 1 and year 4. None of the8 tubule marker levels was higher in the intensive arm compared to the standard arm at year 1 or year 4. Two tubule function markers (B2M and A1M) were 29% (95% CI, 10%-43%) and 24% (95% CI, 10%-36%) lower at year 1 in the intensive versus standard arm, respectively. Exclusion of persons with diabetes, and few participants had advanced CKD. Among participants with CKD in SPRINT, random assignment to the intensive SBP arm did not increase any levels of 8 urine biomarkers of tubule cell damage despite loss of eGFR. These findings support the hypothesis that eGFR declines in the intensive arm of SPRINT predominantly reflect hemodynamic changes rather than intrinsic damage to kidney tubule cells.

Long-term renal outcomes in multi-ethnic Southeast Asians with lupus nephritis: a retrospective cohort study.

Renal involvement is common among Asians with systemic lupus erythematosus and long-term renal outcomes have been described in homogeneous Caucasian and East Asian populations with lupus nephritis, but data are scarce for other ethnicities. To evaluate the incidence and risk factors for progressive chronic kidney disease (CKD) in multi-ethnic Southeast Asians with lupus nephritis. This is a single-centre retrospective cohort study of adults with biopsy-proven lupus nephritis diagnosed between May 2001 and May 2009. Demographic and clinical data were retrieved from electronic medical records. Patients were excluded if baseline comorbid, renal function or pharmacotherapy data were incomplete or if they default follow-up within 3 months from time of diagnosis. Primary outcome was progressive CKD, defined by end-stage renal disease or persistent doubling of serum creatinine or reduction in eGFR ≥50% for ≥3 months from baseline. We studied 113 patients with newly diagnosed biopsy-proven lupus nephritis. Median age was 42 (interquartile range 29-52) years; the majority were Chinese (76%; Malay 13% and others 11%) and female (81%). Two-thirds had International Society of Nephrology and Renal Pathology Society Class III or IV nephritis; serum creatinine was 86 (67-125) μmol/L with heavy proteinuria (6.3 (2.5-12.2) g/g creatinine). Median follow-up was 110 (83-142) months. Remission (partial and complete) occurred in 96% at 3.1 (1.6-5.2) months after diagnosis. Among patients who achieved remission, 56% had disease relapse at 19.0 (6.0-40.2) months after remission. Patients with progressive CKD (n = 13, 11%) had lower baseline CKD Epidemiology Collaboration estimated glomerular filtration rate (37.3 (16.5-82.0) vs 79.4 (57.5-101.0) mL/min/1.73 m2 , P = 0.03) and higher chronicity index (5 (3-6) vs 3 (2-3), P = 0.04) than those who did not. Remission, early remission within 6 months, complete remission and non-relapse were less frequently associated with progressive CKD (P < 0.01). Multi-ethnic Southeast Asians with biopsy-proven lupus nephritis had high remission rates and low incidence of progressive CKD. Progressive CKD was associated with poorer baseline renal function, higher histological chronicity index, failure to achieve remission and occurrence of relapse.

Chronic kidney disease progression in patients with chronic hepatitis B on tenofovir, entecavir, or no treatment.

In clinical trials involving patients with preserved renal function, tenofovir disoproxil fumarate (TDF) use was associated with mild renal impairment in 1% of patients. To compare serial renal function of entecavir (ETV)-treated, TDF-treated, and untreated patients with chronic hepatitis B. We studied the risk of chronic kidney disease (CKD) progression in a territory-wide cohort of patients with chronic hepatitis B without treatment and of those on ETV or TDF treatment. Estimated glomerular filtration rate (eGFR) was determined by the CKD Epidemiology Collaboration equationand was classified into five CKD stages. CKD progression, defined as an increase of at least one CKD stage, was compared among treated and untreated patients. After propensity score matching, 2254 ETV-treated, 2254 TDF-treated, and 2254 untreated patients were included in the analysis. Their mean baseline eGFR was 90.3±19.6, 91.3±20.6, and 92.2±20.0mL/min/1.73m2 , respectively. During a mean follow-up of 2.4±1.5years, 639 ETV-treated, 706 TDF-treated, and 564 untreated patients exhibited CKD progression ≥1 stage. The 5-year cumulative incidence (95% confidence interval) of CKD progression was 43% (40%-46%) in ETV-treated, 48% (45%-51%) in TDF-treated, and 43% (39%-47%) in untreated patients (reference group), respectively (P=0.267 and <0.001, respectively). The number of patients who exhibited CKD progression ≥2 stages was 92 (4.1%) in the untreated cohort, 95 (4.2%) in the ETV-treated cohort, and 51 (2.3%) in the TDF-treated cohort. The use of TDF was associated with mild renal impairment in a minority of patients; those treated with ETV had a similar risk compared to untreated patients.

Moderate Renal Impairment and Toxic Metabolites Produced by the Intestinal Microbiome: Dietary Implications

Toxic metabolites produced by the intestinal microbiome from animal proteins, carnitine (mainly from red meat), or phosphatidylcholine (mainly from egg yolk), have important adverse effects on cardiovascular disease. These are renally eliminated and may be termed gut-derived uremic toxins (GDUT). We hypothesized that even moderate renal impairment and intake of nutrient precursors would raise plasma levels of GDUT. A cohort study. Academic medical center. Patients attending stroke prevention clinics at a university medical center were recruited. Nutrient intake was assessed by the 131-item Harvard Food Frequency Questionnaire; estimated glomerular filtration rate (eGFR) was caculated using the Chronic Kidney Disease-Epidemiology (EPI) equations. Plasma levels of trimethylamine n-oxide, p-cresyl sulfate, hippuric acid, p-cresyl glucuronide, pheny acetyl glutamine, and phenyl sulfate were measured by ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry. Among 316 patients recruited, the mean (standard deviation [SD]) age was 66.74 (10.42) years; 59.7% were men. Mean eGFR was 76.03±20.01; 57 (18%) had eGFR<60mL/min/1.73m2. Plasma levels of all GDUT were significantly higher even with moderate reduction of eGFR. Nutrient intake affected plasma levels of some GDUT; the effects differed by eGFR above and below 60mL/min/1.73m2. Plasma levels were obtained fasting, so we probably underestimated the effect of nutrient intake. Even moderate impairment of renal function was associated with higher plasma levels of GDUT. This has dietary implications for patients at risk of atherosclerosis, particularly in those with impaired renal function (including the elderly): they should limit intake of animal protein, red meat, and egg yolk. It also points the way to novel approaches to vascular prevention, including more intensive dialysis, renal transplantation, and modification of the intestinal microbiome with probiotics or fecal transplantation.

Serum Creatinine and Chronic Kidney Disease-Epidemiology Estimated Glomerular Filtration Rate: Independent Predictors of Renal Replacement Therapy following Cardiac Surgery

Background: Most studies evaluating predictors of renal replacement therapy (RRT) following cardiac surgery use arbitrary defined limits of preoperative serum creatinine. The aim of this study was to evaluate the effect of preoperative renal function using either estimated-glomerular filtration rate (eGFR) derived using Chronic Kidney Disease-Epidemiology (CKD-EPI) or serum creatinine alone as a predictor for RRT after cardiac surgery. Methods: In this prospective cohort study, baseline, intraoperative, and postoperative data of all patients who underwent an elective, urgent, or emergency cardiac surgery between 2012 and 2016 in a single center were analyzed in order to identify multivariate parameters determining the need for RRT after surgery. For preoperative renal function, we used serum creatinine levels and eGFR-derived CKD-EPI equation. We also divided our cohort into eGFR groups following the thresholds of the currently proposed CKD classification. Results: From the 1,614 patients (mean age: 65.4 ± 10.6 years; male: 77.6%) that constituted the study population, 42 (2.6%) underwent RRT postoperatively. EUROSCORE II, cardiopulmonary bypass time, cross clamp time, red blood cell (RBC) units transfused, type and urgency of surgery, combined/non combined operation, peripheral vascular disease, heart failure, chronic obstructive pulmonary disease, dyslipidemia, and preoperative renal function were all univariately associated with RRT use. Multivariate regression with bootstrap utilization indicated that CKD-EPI eGFR (OR 0.979; 95% CI 0.956–0.998), heart failure with the New York Heart Association class ≥2 (OR 4.695; 95% CI 1.756–14.061) and RBC units transfused (OR 1.287; 95% CI 1.081–1.850) were independently associated with RRT need. When serum creatinine (OR 2.920, 95% CI1.056–8.074) was used in the model, the associations with RRT were also significant. Conclusion: Preoperative renal function, defined by serum creatinine or eGFR by CKD-EPI, NYHA class II–IV, and the number of blood units transfused were all independent predictors of RRT postoperatively.

Left Main Revascularization With PCI or CABG in Patients With Chronic Kidney Disease: EXCEL Trial

BackgroundThe optimal revascularization strategy for patients with left main coronary artery disease (LMCAD) and chronic kidney disease (CKD) remains unclear. ObjectivesThis study investigated the comparative effectiveness of percutaneous coronary intervention (PCI) versus coronary artery bypass graft (CABG) surgery in patients with LMCAD and low or intermediate anatomical complexity according to baseline renal function from the multicenter randomized EXCEL (Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) trial. MethodsCKD was defined as an estimated glomerular filtration rate <60 ml/min/1.73 m2 using the CKD Epidemiology Collaboration equation. Acute renal failure (ARF) was defined as a serum creatinine increase ≥5.0 mg/dl from baseline or a new requirement for dialysis. The primary composite endpoint was the composite of death, myocardial infarction (MI), or stroke at 3-year follow-up. ResultsCKD was present in 361 of 1,869 randomized patients (19.3%) in whom baseline estimated glomerular filtration rate was available. Patients with CKD had higher 3-year rates of the primary endpoint compared with those without CKD (20.8% vs. 13.5%; hazard ratio [HR]: 1.60; 95% confidence interval [CI]: 1.22 to 2.09; p = 0.0005). ARF within 30 days occurred more commonly in patients with compared with those without CKD (5.0% vs. 0.8%; p < 0.0001), and was strongly associated with the 3-year risk of death, stroke, or MI (50.7% vs. 14.4%; HR: 4.59; 95% CI: 2.73 to 7.73; p < 0.0001). ARF occurred less commonly after revascularization with PCI compared with CABG both in patients with CKD (2.3% vs. 7.7%; HR: 0.28; 95% CI: 0.09 to 0.87) and in those without CKD (0.3% vs. 1.3%; HR: 0.20; 95% CI: 0.04 to 0.90; pinteraction = 0.71). There were no significant differences in the rates of the primary composite endpoint after PCI and CABG in patients with CKD (23.4% vs. 18.1%; HR: 1.25; 95% CI: 0.79 to 1.98) and without CKD (13.4% vs. 13.5%; HR: 0.97; 95% CI: 0.73 to 1.27; pinteraction = 0.38). ConclusionsPatients with CKD undergoing revascularization for LMCAD in the EXCEL trial had increased rates of ARF and reduced event-free survival. ARF occurred less frequently after PCI compared with CABG. There were no significant differences between PCI and CABG in terms of death, stroke, or MI at 3 years in patients with and without CKD. (EXCEL Clinical Trial [EXCEL]; NCT01205776)

Older Adult Kidney Function Assessment and Rounding Creatinine Led to Medication Dosing Error.

Kidney function assessment in older adults can be unreliable because of many factors, and inaccurate assessment can lead to medication dosing error. Practitioners may have adopted the method of rounding creatinine to an arbitrary number 1.0 because of change in muscle mass and age-related change. This has in fact proven to cause more harm than good, potentially leading to underdosing of many medications. A literature search performed using PubMed with the following key words (rounding serum creatinine, rounding serum creatinine AND pharmacist or pharmacy, rounding serum creatinine AND doctor or physician or healthcare, rounding serum creatinine AND kidney function) with no restrictions (dates or any other requirement). From the PubMed results, articles related to rounding of serum creatinine (Scr) and kidney function assessments were identified and reviewed. Most studies were retrospectives, 1 cross-sectional, 1 meta-analysis, and others were unidentified. These studies included various ways of estimating kidney functions (Tc DTPA clearance, Cockcroft-Gault creatinine clearance, 24-hour urine collection, Modification of Diet in Renal Disease, Chronic Kidney Disease-Epidemiology Collaboration), used various weights (actual body weight, ideal body weight, adjusted body weight), and most studies used 1.0 for rounding up Scr (other studies used 0.8 and 0.85). There was no associated relationship found as related to practicing professions (pharmacists vs. physician) to the practice of rounding Scr. All studies yielded inaccurate kidney function upon rounding of Scr and leading to medication dosing error. All studies suggested against rounding Scr when assessing kidney function in older adults.

Analysis of heterogeneity in kidney function decline in the aged population

Objective To study the rate of kidney function decline and the influencing factors in the aged population. Methods This was a prospective population-based study of 468 participants aged 65 years and older.All participants’ general health information and serum creatinine levels were collected as the baseline.After a 3-year follow-up, the serum creatinine level of each participant was measured again.Kidney function was assessed with estimated glomerular filtration rate (eGFR) calculated using the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation.Outcomes of interest were mean eGFR decline and rapid decline in eGFR (annual eGFR loss≥3 ml·min-1·1.73 m-2). Risk factors were analyzed with Logistic regression. Results At baseline, the mean age of participants was(78.4±8.7)years and the mean eGFR was(74.8 ± 14.5)ml·min-1·1.73 m-2.Annual eGFR decline was 1.5 ml·min-1·1.73 m-2, with rapid declines in 149 (32%) participants and stable kidney function in 319 (68%) individuals.The rate of kidney function loss slowed down as the age increased.Baseline eGFR was an independent predictor for rapid kidney function decline.The incidence of rapid kidney function decline in individuals with eGFR≥60 ml·min-1·1.73 m-2 was 2.40 times (95%CI: 1.16-4.98) higher than that of participants with eGFR<60 ml·min-1·1.73 m-2 after adjustment for confounders. Conclusions Kidney function changes in the community-dwelling elderly in China are heterogeneous.Most elderly individuals do not show appreciable kidney function decline over a 3-year period. Key words: Glomerular filtration rate; Kidney function decline

Fixed But Not Autoadjusting Positive Airway Pressure Attenuates the Time-dependent Decline in Glomerular Filtration Rate in Patients With OSA

The impact of treating OSA on renal function decline is controversial. Previous studies usually included small samples and did not consider specific effects of different CPAP modalities. The aim of this study was to evaluate the respective influence of fixed and autoadjusting CPAP modes on estimated glomerular filtration rate (eGFR) in a large sample of patients derived from the prospective European Sleep Apnea Database cohort. In patients of the European Sleep Apnea Database, eGFR prior to and after follow-up was calculated by using the Chronic Kidney Disease-Epidemiology Collaboration equation. Three study groups were investigated: untreated patients (n= 144), patients receiving fixed CPAP (fCPAP) (n= 1,178), and patients on autoadjusting CPAP (APAP) (n= 485). In the whole sample, eGFR decreased over time. The rate of eGFR decline was significantly higher in the subgroup with eGFR above median (91.42mL/min/1.73 m2) at baseline (P< .0001 for effect of baseline eGFR). This decline was attenuated or absent (P< .0001 for effect of treatment) in the subgroup of patients with OSA treated by using fCPAP. A follow-up duration exceeding the median (541days) was associated with eGFR decline in the untreated and APAP groups but not in the fCPAP group (P< .0001 by two-way ANOVA for interaction between treatment and follow-up length). In multiple regression analysis, eGFR decline was accentuated by advanced age, female sex, cardiac failure, higher baseline eGFR, and longer follow-up duration, whereas there was a protective effect of fCPAP. fCPAP but not APAP may prevent eGFR decline in OSA.

Safety of sofosbuvir-based regimens after liver transplantation: longitudinal assessment of renal function in the prospective ANRS CO23 CUPILT study.

In liver transplant recipients with hepatitis C virus recurrence, there is concern about renal safety of sofosbuvir-based regimens. Changes in serum creatinine or in the estimated glomerular filtration rate (eGFR) under treatment are used to look for possible renal toxicity. However, serum creatinine and eGFR are highly variable. To analyse renal function trajectory with numerous assays of serum creatinine over a long period of time. In a multicentre cohort of 139 patients, the eGFR was obtained from serum creatinine using the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation. Slopes of eGFR were defined as a change in eGFR during a period divided by time. Pre-treatment, on-treatment and post-treatment periods were 9months, 3-9months and 4.5months. Interactions between eGFR slopes and the pre-treatment eGFR, use of ribavirin or mycophenolate mofetil, and stage of fibrosis were addressed. On-treatment eGFR slopes were separated in tertiles. Pre- and post-treatment eGFR slopes were compared globally and according to tertiles. The post-treatment eGFR slope was significantly better than pre-treatment eGFR slope (+0.18 (IQR -0.76 to +1.32) vs -0.11 (IQR -1.01 to +0.73) mL/min/1.73m2 /month, P=0.03) independently of the pre-treatment eGFR (P=0.99), ribavirin administration (P=0.26), mycophenolate mofetil administration (P=0.51) and stage of fibrosis (F3 and F4 vs lower stages, P=0.18; F4 vs lower stages, P=0.08; F4 Child-Pugh B and C vs lower stages, P=0.38). Tertiles of on-treatment eGFR slopes were -1.71 (IQR -2.54 to -1.48), -0.78 (IQR -1.03 to -0.36) and +0.75 (IQR +0.28 to +1.47) mL/min/1.73m2 /month. Pre- and post-treatment eGFR slopes were not significantly different according to tertiles (respectively, P=0.34, 0.08, 0.73). The eGFR varies during treatment and gives a confusing picture of the renal safety of sofosbuvir-based regimens. In contrast, longitudinal assessment of the eGFR shows a rising trajectory over longer time, meaning that these therapies are safe for the kidneys in our cohort of liver transplant recipients.

Reclassification of Chronic Kidney Disease Stage, Eligibility for Cystatin-C and Its Associated Costs in a UK Primary Care Cohort

Background and Aims: Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) estimations of glomerular filtration rate (eGFR), compared to modification of diet in renal disease (MDRD), have superior performance in predicting renal, cardiovascular and mortality events. Cystatin-C further improves prediction. Our primary aim was to assess the change in prevalence and classification of CKD in converting from MDRD to CKD-EPI in an unselected primary care CKD population. Our secondary aims were to determine the eligibility for cystatin-C testing based on National Institute for Health and Care Excellence guidance and the associated costs. Methods: eGFR data from an unselected UK primary care CKD cohort was studied to assess reclassification of CKD stages from MDRD to CKD-EPI, suitability for cystatin-C testing and its associated cost. Results: A total number of 24,660 individuals had ≥2 MDRD eGFR results <60 mL/min/1.73 m² >3 months apart (7.0% of adult population). The mean age was 75.2 (SD 11.4 years) with 15,265 (61.9%) females. Mean eGFR was 2.88 mL/min/1.73 m² lower with CKD-EPI eGFR versus MDRD eGFR (49.7 vs. 46.8, t test p < 0.0001, 95% CI 2.85–2.91). 12.0% of individuals were re-categorised to a more or less advanced CKD stage, and 1.3% to a less advanced stage. The percentage of the population categorised as 3a-A1 CKD-EPI and therefore potentially suitable for cystatin-C was 2.8%. The estimated initial cost is €67.5 (£57.2) million with annual costs of €2.7 (£2.3) million for the United Kingdom. Conclusions: The mean eGFR was lower with the CKD-EPI formula and individuals were more likely to be reclassified to more advanced CKD. This may be related to the higher mean age of this unselected population compared to previous studies. Refinements of eGFR formulae, CKD definitions and cystatin-C eligibility in unselected populations are required.

Abstract MP11: Serum Metabolites Associate With Kidney Function Among Bogalusa Heart Study Participants

Chronic kidney disease (CKD) is an important public health challenge due to its high prevalence, potential for progression to end-stage renal disease, and associated increases in risks of cardiovascular disease morbidity and mortality. While traditional risk factors for reduced kidney function have been identified, the biological pathways underlying this complex phenotype remain largely unknown. A metabolome-wide association study was conducted among 825 white and 436 African-American participants of the Bogalusa Heart Study (BHS) to identify metabolites associated with kidney function. Estimated glomerular filtration rate (eGFR) was calculated among BHS participants using the CKD Epidemiology Collaboration (CKD-EPI) equation. Untargeted, ultra-high performance liquid chromatography tandem-mass spectroscopy was used to quantify 1,466 metabolites. A total of 1,202 metabolites passing rigorous quality control were tested for association with eGFR in race stratified and combined multiple regression analyses that adjusted for age, sex, education, cigarette smoking, alcohol drinking, physical activity, body mass index, and race (in combined analyses). Significant metabolites were identified as those achieving Bonferroni corrected significance (P&lt;4.16х10 -5 ) in one race group and the entire cohort, with a similar trend observed in the other race group. Results of these analyses are presented in the Figure . Among 302 significant metabolites, 89 were novel and in known metabolic pathways, 106 were novel and in unknown metabolic pathways, and 107 were previously reported. The 89 novel metabolites were classified into the following pathways: 40 in amino acids, 3 in carbohydrates, 7 in cofactors, 1 in energy, 6 in nucleotides, 9 in peptides, and 14 in xenobiotics. In conclusion, the current analysis not only validated previous findings, but identified novel metabolites associated with kidney function. These data provide important insights into the biological pathways underlying this complex phenotype.

Performance of glomerular filtration rate estimation equations in Congolese healthy adults: The inopportunity of the ethnic correction.

Context and objectiveIn the estimation of glomerular filtration rate (GFR), ethnicity is an important determinant. However, all existing equations have been built solely from Caucasian and Afro-American populations and they are potentially inaccurate for estimating GFR in African populations. We therefore evaluated the performance of different estimated GFR (eGFR) equations in predicting measured GFR (mGFR).MethodsIn a cross-sectional study, 93 healthy adults were randomly selected in the general population of Kinshasa, Democratic Republic of the Congo, between June 2015 and April 2016. We compared mGFR by plasma clearance of iohexol with eGFR obtained with the Modified Diet in Renal Disease (MDRD) equation with and without ethnic factor, the Chronic Kidney Disease Epidemiology (CKD-EPI) serum creatinine (SCr)-based equation, with and without ethnic factor, the cystatin C-based CKD-EPI equation (CKD-EPI SCys) and with the combined equation (CKD-EPI SCrCys) with and without ethnic factor. The performance of the equations was studied by calculating bias, precision and accuracy within 30% (P30) of mGFR.ResultsThere were 48 women and 45 men. Their mean age was 45.0±15.7 years and the average body surface area was 1.68±0.16m2. Mean mGFR was 92.0±17.2 mL/min/1.73m2 (range of 57 to 141 mL/min/1.73m2). Mean eGFRs with the different equations were 105.5±30.1 and 87.2±24.8 mL/min/1.73m2 for MDRD with and without ethnic factor, respectively; 108.8±24.1 and 94.3x20.9 mL/min/1.73m2 for CKD-EPI SCr with and without ethnic factor, respectively, 93.5±18.6 mL/min/1.73m2 for CKD-EPI SCys; 93.5±18.0 and 101±19.6 mL/min/ 1.73m2 for CKD-EPI SCrCys with and without ethnic factor, respectively. All equations slightly overestimated mGFR except MDRD without ethnic factor which underestimated by -3.8±23.0 mL/min /1.73m2. Both CKD-EPI SCr and MDRD with ethnic factors highly overestimated mGFR with a bias of 17.9±19.2 and 14.5±27.1 mL/min/1.73m2, respectively. There was a trend for better P30 for MDRD and CKD-EPI SCr without than with the ethnic factor [86.0% versus 79.6% for MDRD (p = 0.21) and 81.7% versus 73.1% for the CKD-EPI SCr equations (p = 0.057)]. CKD-EPI SCrCys and CKD-EPI SCys were more effective than creatinine-based equations.ConclusionIn the Congolese healthy population, MDRD and CKD-EPI equations without ethnic factors had better performance than the same equations with ethnic factor. The equations using Cys C (alone or combined with SCr) performed better than the creatinine-based equations.

Sex and gender disparities in the epidemiology and outcomes of chronic kidney disease.

Improved understanding of sex and gender-specific differences in the aetiology, mechanisms and epidemiology of chronic kidney disease (CKD) could help nephrologists better address the needs of their patients. Population-based studies indicate that CKD epidemiology differs by sex, affecting more women than men, especially with regard to stage G3 CKD. The effects of longer life expectancy on the natural decline of glomerular filtration rate (GFR) with age, as well as potential overdiagnosis of CKD through the inappropriate use of GFR equations, might be in part responsible for the greater prevalence of CKD in women. Somewhat paradoxically, there seems to be a preponderance of men among patients starting renal replacement therapy (RRT); the protective effects of oestrogens in women and/or the damaging effects of testosterone, together with unhealthier lifestyles, might cause kidney function to decline faster in men than in women. Additionally, elderly women seem to be more inclined to choose conservative care instead of RRT. Dissimilarities between the sexes are also apparent in the outcomes of CKD. In patients with predialysis CKD, mortality is higher in men than women; however, this difference disappears for patients on RRT. Although access to living donor kidneys among men and women seems equal, women have reduced access to deceased donor transplantation. Lastly, health-related quality of life while on RRT is poorer in women than men, and women report a higher burden of symptoms. These findings provide insights into differences in the underlying pathophysiology of disease as well as societal factors that can be addressed to reduce disparities in access to care and outcomes for patients with CKD.

Sodium excretion and associated factors in urine samples of African descendants in Alcântara, Brazil: a population based study

In most countries, salt intake has been excessive and constitutes one of the main risk factors for disease development, especially hypertension. Factors such as age, gender, sedentary lifestyle, smoking, African descent, obesity, dietary habits and family history of hypertension may be associated with high blood pressure. Studies show a positive association between the excretion of sodium and increased blood pressure. We evaluated the urinary excretion of sodium and associated factors in isolated urine samples of African descendants from remaining Quilombos. We performed a cross-sectional, population-based study with 1162 African descendants living in remaining quilombos in Alcântara, Maranhão, Brazil. Demographic, nutritional, clinical and laboratory data were analyzed. Urinary sodium excretion was estimated using the Kawasaki equation. A multivariate linear regression model was used to identify the variables related to sodium excretion. The average age was 37.6 ± 11.8 years and 51.2% were women. The prevalence of hypertension was 21.3%. The average urinary excretion of sodium was high, especially among the hypertensive (217.9 ± 90.1 vs. 199.2 ± 83.0 mmol/d; p = .002). After an adjusted analysis, only the waist circumference (odds ratios (OR) = 1.16; confidence intervals(CI)95%: 1.03–1.30), triglyceride (OR = 1.13; CI95%: 1.05–1.22), systolic blood pressure (OR = 1.19; CI95%: 1.08–1.32) and Chronic Kidney Disease Epidemiology (CKD-EPI;OR = 1.24; CI95%: 1.15–1.35) remained related to urinary sodium excretion. African descendants had a high rate of sodium excretion, especially among those who had hypertension. Abdominal adiposity, triglyceride and systolic blood pressure levels and renal function by CKD-EPI equation were associated to urinary sodium excretion.

Relationship of Creatinine and Cystatin C-based Estimated Glomerular Filtration rates with Measured Glomerular Filtration Rate in Healthy Kidney Donors from South Asia.

Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation is currently recommended for the estimation of glomerular filtration rate (GFR). This retrospective study aimed to evaluate the correlation between creatinine and cysC-based estimated GFRs and measured GFR in healthy adults. Consecutive healthy adults who were accepted as voluntary kidney donors at our center between January 2008 and December 2012 were included in the study. The 336 individuals who comprised the study population had a mean age of 41.6 ± 11.8 years, male:female ratio 1:1.7, mean creatinine 0.9 ± 0.1 mg/dl, and mean cysC 0.8 ± 0.1 mg/dl. Mean measured GFR by Tc-99m diethylenetriaminepentaacetic acid using Gates method was 98.4 ± 21.2 ml/min/1.73 m2. The mean ± standard deviation of eGFRs by various formulae were as follows: Cockcroft–Gault (CG) = 88.1 ± 15.9 ml/min/1.73 m2, Modification of Diet in Renal Disease (MDRD) = 78 ± 14.7 ml/min/1.73 m2, CKD-EPI creatinine = 88.1 ± 15.5 ml/min/1.73 m2, CKD-EPI cysC = 97 ± 19.9 ml/min/1.73 m2, CKD-EPI creatinine-cysC (CKD-EPI cr-cysC) = 92.5 ± 14.1 ml/min/1.73 m2. The CKD-EPI cr-cysC equation had the highest accuracy, with 43% and 72% of values lying within ±10% and ±20% of the measured GFR, respectively. Bland–Altman analyses for levels of agreement showed least bias with CKD-EPI cysC overall and among females, while among males, CKD-EPI creatinine equation had the least bias. The CKD-EPI equation showed a higher performance than the MDRD and CG equation in GFR estimation of a healthy population. Among CKD-EPI equations, CKD-EPI cr-cysC had the highest accuracy and CKD-EPI cysC the least bias.

MDRD vs. CKD-EPI in comparison to 51Chromium EDTA: a cross sectional study of Malaysian CKD cohort

BackgroundAccurate measurement of renal function is important: however, radiolabelled gold standard measurement of GFR is highly expensive and can only be used on a very limited scale. We aim to compare the performance of Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equations in the multi-ethnic population attending University Malaya Medical Centre (UMMC).MethodsThis is a cross-sectional study recruiting patients, who attend UMMC Nephrology clinics on voluntary basis. 51-Chromium EDTA (51Cr-EDTA) plasma level was used to measure the reference GFR. The serum creatinine was determined by IDMS reference modified Jaffe kinetic assay (CrJaffe). The predictive capabilities of MDRD and CKD-EPI based equations were calculated. Data was analysed using SPSS version 20 and correlation, bias, precision and accuracy were determined.ResultsA total of 113 subjects with mean age of 58.12 ± 14.76 years and BMI of 25.99 ± 4.29 kg/m2 were recruited. The mean reference GFR was 66.98 ± 40.65 ml/min/1.73m2, while the estimated GFR based on MDRD and CKD-EPI formula were 62.17 ± 40.40, and 60.44 ± 34.59, respectively. Both MDRD and CKD-EPI were well-correlated with reference GFR (0.806 and 0.867 respectively) and statistically significant with p < 0.001. In the overall cohort, although MDRD had smaller bias than CKD-EPI (4.81 vs. 6.54), CKD-EPI was more precise (25.22 vs. 20.29) with higher accuracy within 30% of measured GFR (79.65 vs. 86.73%).ConclusionThe CKD-EPI equation appeared to be more precise and accurate than the MDRD equation in estimating GFR in our cohort of multi-ethnic populations in Malaysia.

Epidemiology, Health Economic Context, and Management of Chronic Kidney Diseases in Low and Middle-Income Countries: The Case of Morocco

Background: There is a significant emerging burden of chronic kidney disease (CKD) and end-stage renal disease (ESRD) in low and middle-income countries. Nonetheless, despite these trends, knowledge of CKD epidemiology and management remains incomplete. This review presents a critical analysis and comparison of the current data related to CKD epidemiology in Morocco and an overview of the health economic context of the management of ESRD. Main text: In Morocco, the demographic transition occurring as a result of urbanisation, population ageing, and the global epidemic of diabetes exposes a growing number of people with CKD who are consuming a significant proportion of healthcare budgets. While the real prevalence of ESRD may be underestimated due to limited access to medical coverage for a fraction of the population, the growing costs in the face of limited resources may shortly compromise the healthcare system. Conclusion: Based on the available data, the prevalence of CKD may grow during the coming decades, according to the increasing prevalence of its major risk factors (diabetes, hypertension, and older age). Thus, early diagnosis, treatment of the underlying cause, and implementation of preventive measures are fundamental for CKD patients.

Pre-operative and post-operative estimated glomerular filtration rate in Japanese patients with urological malignancies.

The suitable methods evaluating glomerular filtration rate (GFR) have not been established in patients undergoing radical nephrectomy (RN) or radical nephroureterectomy (RNU) due to urological malignancies in Japan as well as worldwide. We examined the relationship between creatinine clearance-based measured GFR (mGFR) versus estimated GFR (eGFR) calculated by 3 popular equations, 4-variable Modification of Diet in Renal Disease equation adjusted by Japanese correction coefficient (cmMDRD), 3-variable MDRD equation for Japanese population (eGFRcreat), and Chronic Kidney Disease-Epidemiology Collaboration equation adjusted by Japanese correction coefficient (cmCKD-EPI) in Japanese patients who had undergone RN or RNU due to renal cell carcinoma or upper tract urothelial carcinoma before and after surgery. Among the 3 equations examined, eGFRcreat was the closest to mGFR, although each eGFR was significantly higher than mGFR in the pre-operative period. In the post-operative period, cmMDRD and eGFRcreat, but not cmCKD-EPI, were comparable to mGFR. Each of eGFR was significantly correlated with mGFR in both the pre-operative and post-operative periods. Similar results were obtained by the subanalysis of the patients with pre-operative mGFR of < 60mL/min/1.73m2. Results of κ statistics also showed that eGFRcreat was most appropriate to estimate GFR both before and after heminephrectomy, when cut-off value of GFR of < 60mL/min/1.73m2 was used. Results of the present study suggest that eGFRcreat is likely to be the most appropriate equation for patients undergoing RN or RNU due to urological malignancies. However, more precise equations will be required for accurately estimating GFR.

Selection and Short-Term Outcomes of Living Kidney Donors in Singapore – An Analysis of the Donor Care Registry

Transplant rates in Singapore have been falling and there is limited information on baseline characteristics and clinical outcomes of living kidney donors nationally. This study aimed to determine the safety of living kidney donor transplant in Singapore by exploring the proportion of donors that meets international selection guidelines and describing short-term clinical outcomes. We analysed 472 donors who underwent nephrectomies from 1 January 2010 to 31 December 2014 from the Donor Care Registry. We described donor characteristics against 5 international guidelines and measured post-nephrectomy outcomes in 150 local donors for up to 24 months. A multivariate analysis was performed to determine the baseline variables associated with poorer outcomes. There were more foreign than local donors, with differences in gender and hospital types. Selection was generally aligned with international recommendations although 3.0% (using the Chronic Kidney Disease Epidemiology [CKD-EPI] equation) to 8.5% (using radionuclide and creatinine clearance methods) of donors had inappropriate baseline estimated glomerular filtration rates (eGFR) forage. Post-procedure, many foreign donors were lost to follow-up. Over 24 months, eGFR decreased by 33.8% from baseline before recovering gradually to 29.6%. During this period, only 2 donors were admitted for renal or urological conditions and there were no cases of end-stage renal failure or deaths. A lower baseline eGFR (HR: 1.05; 95% Cl, 1.02 to 1.09) and older age (HR: 1.04; 95% Cl, 1.00 to 1.08) were associated with a post-nephrectomy eGFR of less than 60 mL/kg/1.73 m2. Kidney donation is safe in Singapore. Donor selection is in keeping with international guidelines and short-term outcomes are comparable to other cohorts.