Higher Risk Of Chronic Kidney Disease Progression Research Articles

Association between health related quality of life and progression of chronic kidney disease

The impact of health-related quality of life (HRQOL) on outcomes remains unclear in chronic kidney disease (CKD) patients despite its importance in socioeconomic aspects and individual health. We aim to identify the relationship between HRQOL and progression of CKD in pre-dialysis patients. A total 1622 patients with CKD were analyzed in the KoreaN cohort Study for Outcomes in patients With Chronic Kidney Disease, a prospective cohort study. CKD progression was defined as one or more of the following: initiation of dialysis or transplantation, a two-fold increase in baseline serum creatinine levels, or a 50% decline in the estimated glomerular filtration rate during the follow-up period. The group with CKD progression had lower scores of HRQOL than the group without CKD progression. A fully adjusted Cox proportional hazard ratio model showed that each low baseline physical and mental component summary score was associated with a higher risk of CKD progression. In Kaplan-Meier survival analysis using propensity score matched data, only low physical component summary scores showed statistical significance with CKD progression. Our study highlights low physical component summary score for an important prognostic factor of CKD progression. Risk-modification interventions for high-risk patients may provide benefits to individuals.

Cardiovascular and nephrological risk in patients with chronic kidney disease in ambulatory care.

Patients with chronic kidney disease (CKD) have higher than in general population all-cause and cardiovascular mortality. Arterial hypertension (HTN) is a powerful potentially modifiable risk factor that affects the majority of patients with chronic kidney disease and one of the main causes of end stage renal disease worldwide. Existing tools for assessment of risk of CKD progression do not take into account arterial hypertension. The aim – to investigate the association between cardiovascular and nephrological risk factors in patients with CKD in ambulatory practice. The study was carried out in the Center of Nephrology Care in Mechnikov Dnipropetrovsk Regional Hospital, Dnipro, Ukraine. 278 patients (114 males and 164 women, aged 41 [31;61] years) with CKD (stages 1-3) who were followed-up in ambulatory care, but required diagnosis or treatment revision were enrolled to the study. All patients were examined and followed-up according to local and European standards. Females slightly prevailed in our study, gender distribution varied insufficiently in groups by CKD progression risk. Elevation of risk of CKD progression was accompanied by rise of prevalence of diabetes mellitus, left ventricle hypertrophy, proteinuria and HTN. Risk of CKD progression correlated with age, systolic and diastolic blood pressure, erythrocyte sedimentation rate, total cholesterol, glomerular filtration rate, albumin excretion rate, duration of HTN and body mass index. Rise of cardiovascular risk was accompanied by rise of proportion of patients with high risk of CKD progression. Increase in risk of CKD progression is associated with rise of burden of cardiovascular risk factors. HTN and blood pressure values should be accounted for assessment of risk of CKD progression.

SAT-173 RISK FACTORS AND DEFINITION OF KIDNEY DYSFUNCTION IN THE COMMUNITY SETTING: THE ISN 0BY25 INITIATIVE

Community-acquired acute kidney injury (CA-AKI) is common, but often unrecognized in resource- constrained settings. Risk factors for CA-AKI development have not been well studied in Low and Lower-Middle Income Countries (LLMIC). A key limitation is the heterogeneity of diseases and a lack of a standardized approach to evaluating renal dysfunction. Limited lab assessments and lack of information on the prior state of kidney health contribute to this lack of recognition. In this study, we evaluated the risk factors associated with acute kidney disease (AKD) and the efficacy of point of care (POC) serum creatinine (sCr) and urine dipstick tests to identify patients with kidney dysfunction at presentation to community health centers (CHC) and emergency departments (ED), as part of the International Society of Nephrology (ISN) 0by25 Pilot Feasibility Project. Patients (pts) presenting at CHC or ED were screened for signs or symptoms a priori associated with high/moderate risk of developing AKI. When presentation suggested AKI risk, they underwent an sCr POC test and a urine protein dipstick.At enrollment, pts were classified as chronic kidney disease (CKD) based on prior history, proteinuria (>1+) and/or baseline sCr within 12 mos by estimated GFR (CKD- EPI equation)) <60 mL/min/1.73 m2; normal renal function (NRF) (no proteinuria and eGFR >75ml/min/1.73 m2); and AKD neither meeting criteria for CKD or NRF. AKI was confirmed within 7 days by sCr increase or decrease of 0.3 mg/dl or 1.5x from the enrollment value. Pt outcomes: progression of AKI, need for RRT, hospitalization, mortality and renal functional recovery, were assessed at 7days and 1, 3 and 6 mos. 3577 pts were screened, 2101 enrolled; 91% adults, 9% children. At enrollment, 9% were CKD and 66% AKD. At 7 days, 30% of pts fulfilled criteria for AKI: 67 from NRF (13%), AKD 470 (33%) and CKD 91 (46%). In comparison to NRF, patients with AKD had a higher frequency of diabetes mellitus, hypertension, and chronic liver disease. The use of ACEI, tenofovir, and antibiotics other than aminoglycosides was more frequent in patients with AKD and AKI. Dehydration associated with vomiting and low oral intake was the most common risk factor for AKD, followed by diarrhea, hypotension and appetite loss. Mortality at discharge and at 6 months was 5% and 13%, respectively, 3.4% and 6.4% in those with no renal dysfunction, 3.1% and 13.7% in those with AKI, 7.3 % and 16.1% in those with AKD and 10.3% and 24.5% in those with CKD. Of 434 patients with 3 months sCr follow up, new onset CKD was encountered in 40 (26%) of AKD and 54 (33%) of AKI patients. Of patients dying from CKD and AKD groups, non-provision of dialysis occurred in 31 (11%). Community-acquired AKI is common in low resource settings. Comorbidities and a set of signs and symptoms can identify adult patients at risk for AKD and can be used to select patients that may benefit from sCr POC testing and protein dipstick in CHC and ED settings. POC creatinine and urine dipstick tests identified a significant number of patients with AKD that would otherwise go unrecognized. Applying the AKD criteria can help to identify patients with a higher risk of CKD progression and a higher mortality rate. Patients with AKD have threefold higher mortality than patients with normal renal dysfunction.

Fasting Urinary Osmolality, CKD Progression, and Mortality: A Prospective Observational Study

Chronic kidney disease (CKD) characterized by decreased glomerular filtration rate (GFR) is often accompanied by various degrees of impaired tubular function in the cortex and medulla. Assessment of tubular function may therefore be useful in establishing the severity of kidney disease and identifying those at greater risk for CKD progression. We explored reductions in urinary concentrating ability, a well-known feature of CKD, as a risk factor for GFR decline and end-stage renal disease (ESRD). Prospective longitudinal cohort study. 2,084 adult patients with CKD stages 1 to 4 from the French NephroTest Cohort Study. Fasting urinary osmolality measured using delta cryoscopy. ESRD, mortality before ESRD, and measured GFR (mGFR) assessed using 51Cr-EDTA renal clearance. Cause-specific hazards models were fit to estimate crude and adjusted associations of urinary osmolality with ESRD and death before ESRD. Linear mixed models with random intercepts were fit to evaluate the association of urinary osmolality with slope of decline in mGFR. At baseline, mean age was 58.7±15.2 (SD) years with a median mGFR of 40.2 (IQR, 29.1-54.5) mL/min/1.73m2 and a median fasting urinary osmolality of 502.7±151.7mOsm/kg H2O. Baseline fasting urinary osmolality was strongly associated with mGFR (R=0.54; P< 0.001). 380 ESRD events and 225 deaths before ESRD occurred during a median follow-up of 5.9 (IQR, 3.8-8.2) years. Patients with lower baseline fasting urinary osmolality had higher adjusted risk for ESRD but not for mortality (HRs of 1.97 [95% CI, 1.26-3.08] and 0.99 [95% CI, 0.68-1.44], respectively, for the lowest vs highest tertile). Based on a mixed linear model adjusted for baseline mGFR and clinical characteristics, patients in the lowest tertile of baseline urinary osmolality had a steeper decline in kidney function (-4.9% ± 0.9% per year; P< 0.001) compared with patients in the highest tertile. Fasting was self-reported. Fasting urinary osmolality may be a useful tool, in addition to GFR and albuminuria, for assessing nonglomerular damage in patients with CKD who are at higher risk for CKD progression.

Tolerance to Sodium in Patients With CKD-Induced Metabolic Acidosis: Does the Accompanying Anion Matter?

Patients with chronic kidney disease (CKD) continue to produce endogenous acids but have a reduction in net acid excretion, resulting in a primary decrease in serum bicarbonate concentration, which is termed chronic metabolic acidosis. Recent prospective studies, along with retrospective cohort analyses, demonstrate a higher risk for CKD progression with untreated metabolic acidosis. To normalize serum bicarbonate levels, acidemic patients are often treated with sodium bicarbonate (NaHCO3) or sodium citrate, which have been shown to slow the progression of CKD. However, studies using this approach have routinely excluded patients with common sodium-sensitive comorbid conditions, such as poorly controlled hypertension, congestive heart failure, volume overload, or edema. This article examines the effect of the anion that accompanies sodium delivered with these therapies. Do the negative effects on blood pressure (BP) and sodium retention, as measured by an increase in edema, weight gain, and congestive heart failure, observed with oral administration of sodium chloride (NaCl) differ when a similar amount of sodium is given with bicarbonate or citrate in this patient population? A review of the literature suggests that NaHCO3 does not increase BP or sodium retention when administered to patients with CKD during a concurrent severe NaCl dietary restriction (∼10 mEq/d). However, this degree of NaCl restriction is feasible only under strict control in clinical research environments. In contrast, when NaHCO3 is given to patients without severe dietary NaCl restriction, there is an increase in BP and sodium retention. Thus, unless patients with CKD can tolerate a diet virtually devoid of NaCl, additional sodium, regardless of the accompanying anion, appears to increase BP and sodium retention.

Hematuria as a risk factor for progression of chronic kidney disease and death: findings from the Chronic Renal Insufficiency Cohort (CRIC) Study

BackgroundHematuria is associated with chronic kidney disease (CKD), but has rarely been examined as a risk factor for CKD progression. We explored whether individuals with hematuria had worse outcomes compared to those without hematuria in the CRIC Study.MethodsParticipants were a racially and ethnically diverse group of adults (21 to 74 years), with moderate CKD. Presence of hematuria (positive dipstick) from a single urine sample was the primary predictor. Outcomes included a 50% or greater reduction in eGFR from baseline, ESRD, and death, over a median follow-up of 7.3 years, analyzed using Cox Proportional Hazards models. Net reclassification indices (NRI) and C statistics were calculated to evaluate their predictive performance.ResultsHematuria was observed in 1145 (29%) of a total of 3272 participants at baseline. Individuals with hematuria were more likely to be Hispanic (22% vs. 9.5%, respectively), have diabetes (56% vs. 48%), lower mean eGFR (40.2 vs. 45.3 ml/min/1.73 m2), and higher levels of urinary albumin > 1.0 g/day (36% vs. 10%). In multivariable-adjusted analysis, individuals with hematuria had a greater risk for all outcomes during the first 2 years of follow-up: Halving of eGFR or ESRD (HR Year 1: 1.68, Year 2: 1.36), ESRD (Year 1: 1.71, Year 2: 1.39) and death (Year 1:1.92, Year 2: 1.77), and these associations were attenuated, thereafter. Based on NRIs and C-statistics, no clear improvement in the ability to improve prediction of study outcomes was observed when hematuria was included in multivariable models.ConclusionIn a large adult cohort with CKD, hematuria was associated with a significantly higher risk of CKD progression and death in the first 2 years of follow-up but did not improve risk prediction.

Dietary Potential Renal Acid Load and Risk of Albuminuria and Reduced Kidney Function in the Jackson Heart Study

Diets high in sulfur-rich protein and low in fruit and vegetables affect human acid-base balance adversely and may have a harmful effect on progression of chronic kidney disease (CKD). Little is known about the relationship of participant characteristics, dietary acid load (DAL), and kidney injury in African-Americans with high risk of CKD progression. We examined the association of DAL with CKD in 3,257 African-Americans aged >20years in Jackson Heart Study. DAL was measured with nutrient intakes assessed with a food frequency questionnaire, using a model described by Remer and Manz. We tested associations of participant characteristics with DAL using median regression, and associations of DAL with albuminuria (>17mg/g for men, >25mg/g for women), reduced kidney function (eGFR <60mL/minute/1.73m2), or CKD defined as albuminuria or reduced kidney function using logistic regression. We further explored whether endothelin and aldosterone production in participants with hypertension mediated risk of albuminuria or reduced kidney function due to the intake of an acid-inducing diet. Younger adults, men, and those with higher body mass index had higher DAL. Higher DAL, compared with lower, was associated with greater odds of reduced kidney function (OR [95% CI]: 2.82 [1.40-4.75]). Higher DAL was also associated with greater risk of CKD, and this persisted after adjustment for confounders. Results were similar in adults with hypertension; the OR [95% CI] for highest, versus lowest, tertile of DAL with albuminuria was 1.66 [1.01-2.59]. Aldosterone and endothelin mediated the association between DAL and albuminuria; the OR [95% CI] in the highest tertile was no longer significant 1.53 [0.97-2.40] after their inclusion. Higher DAL was associated with higher prevalence of CKD and with reduced kidney function. DAL may be an important target for future interventions in African-Americans at high risk of CKD.

Abstract MP07: Soluble Urokinase-type Plasminogen Activator Receptor is associated with progression of hypertension-attributed chronic kidney disease in African Americans

Introduction: Soluble urokinase-type plasminogen activator receptor (suPAR), a circulating signaling protein and marker of immune activation, has been linked to incident and progressive chronic kidney disease (CKD) in select patient populations, often with few African Americans. Hypothesis: We assessed the hypothesis that higher circulating levels of suPAR are associated with risk for progression of hypertension-attributed CKD in African Americans. Methods: We quantified baseline plasma levels of suPAR in participants of the African-American Study of Kidney Disease and Hypertension (AASK), a clinical trial of African Americans with hypertension-attributed CKD, and regular assessment of measured glomerular filtration rate (mGFR), and proteinuria. We used Cox proportional hazards regression to assess the associations of suPAR with CKD progression (defined as doubling of serum creatinine or end-stage renal disease [ESRD]), ESRD, worsening proteinuria (pre-ESRD doubling of 24-hour urine protein to creatinine ratio [UPCR] to ≥220 mg/g), and all-cause death. Results: Among 955 AASK participants, the median baseline suPAR was 4462 pg/mL (25 th to 75 th percentile: 3425-5923 pg/mL), mean mGFR was 46 mL/min per 1.73 m 2 , and median 24-hour UPCR was 79.6 mg/g. After controlling for baseline demographics, AASK trial arm, mGFR, proteinuria, APOL1 risk status, and clinical risk factors, there was a 1.42-times higher risk for CKD progression per two-fold higher baseline suPAR (HR 1.42, 95% CI: 1.17-1.71, p &lt;0.001). Higher suPAR was also independently associated with ESRD (HR 1.59, 95% CI: 1.26-2.00, p &lt;0.001) and death (HR 1.40, 95% CI: 1.12-1.75, p =0.003). Only in patients with two APOL1 risk alleles was suPAR associated with worsening proteinuria (HR 1.77, 95% CI 1.11-2.82, p =0.016; p interaction =0.008). Conclusion: Our study provides evidence of associations between higher suPAR levels and risk for various adverse outcomes in African Americans with hypertension-attributed CKD, independent of proteinuria and GFR.

THE PREVALENCE OF CHRONIC KIDNEY DISEASE MARKERS IN ARTERIAL HYPERTENSION PATIENTS AND RELATION WITH DIABETES: RESULTS OF EPIDEMIOLOGICAL STUDY KHRONOGRAPH

Aim. Under the framework of non-interventional observational multi-center program KHRONOGRAPH (Acquisition of additional data on the prevalence of declined glomerular filtration rate and albuminuria in systemic hypertension patients with and with no diabetes mellitus type 2 in Russian Federation) to evaluate the prevalence of chronic kidney disease (CKD) markers. Material and methods. In 1363 patients with arterial hypertension (AH) and/or type 2 diabetes (DM2) the glomerular filtration rate (GFR) was calculated with CKD-EPI, and albuminuria (AU) assessed via albumin/creatinine ratio (ACr) in morning urine. Results. In DM2 patients (n=779, 62,6% women, 63,8 y. o.) comparing to non-DM2 patients (n=584, 50,7% women, 60,5 y. o.) there was more common decrease of GFR &lt;60 mL/min/1,73 m 2 (38 and 31%), &lt;45 mL/min/1,73 m 2 (G3b-G5) (15,92 and 9,94%) and &lt;30 mL/min/1,73 m 2 (G4-G5) (4,24 and 2,06%), high and very high AU (36,6 and 28,1%), very high AU (А3) — (7,32 and 2,40%). In DM2 patients there was more common presence of at least one marker of CKD &lt;60 mL/min/1,73 m 2 and/or ACr &gt;30 mg/g) (54,0 and 44,35%), isolated GFR decrease &lt;60 mL/min/1,73 m 2 (17,46 and 16,27%), isolated increase of ACr &gt;30 mg/g (15,66 and 13,35%) and combination of decreased GFR and high/very high AU (20,93 and 14,71%). Among DM2 patients, the portion is lower of decreased combination risk of CKD progression and cardiovascular complications (45,2 and 53,6%), higher — in very high risk (28,5 and 20%). Most prevalent are the combinations related to early stages of CKD: G3аА1, G2А2 and G3аА2. Conclusion. In Russian Federation, patients with AH, regardless of DM2, are characterized by high rate of CKD markers. In DM2 patients comparing to those with none, there was more prevalent GFR decrease &lt;60 mL/min/1,73 m 2 , increase of ACr &gt;30 mg/g isolated and in combination. In AH and DM2 the portion of patients with a very high risk of CKD progression and cardiovascular complications is higher.

The CHA2DS2-VASc score strongly correlates with glomerular filtration rate and predicts renal function decline over time in elderly patients with atrial fibrillation and chronic kidney disease

BackgroundThe decline of renal function affects stroke risk in patients with atrial fibrillation (AF). Here, we aim to study the predictive value of the CHA2DS2-VASc score, a stroke-risk stratification model in AF, for renal function and renal decline in patients with AF and chronic kidney disease (CKD). MethodsTwo electronic health record cohorts with AF and CKD stage III/IV were evaluated (Cohort #1 (IMS-DA, Germany): 18,539 patients with 125,149 estimated glomerular filtration rate (eGFR) measurements; Cohort #2 (IMS-THIN, United Kingdom): 18,240 patients with 133,676 eGFR measurements). The eGFR trajectories were analysed with multi-level mixed-effects regression and joint models for longitudinal and survival data. ResultsIn IMS-DA, the mean baseline eGFR was 52.0ml/min/1.73m2, and declined by 1.03ml/min/1.73m2/year (95%CI: 0.86–1.19, p<0.0001). In IMS-THIN, the mean baseline eGFR was 48.0ml/min/1.73m2, and declined by 0.44ml/min/1.73m2/year (95%CI: 0.37–0.51, p<0.0001).In both datasets, higher CHA2DS2-VASc scores (median: 4 points) were strongly associated with both lower baseline eGFR (p<0.0001) and faster progression of CKD (p=0.002). Mean baseline eGFR values were higher in patients with a CHA2DS2-VASc score of 0 compared to patients with a score of 8 points. Conversely, the annual declines in eGFR were lower in patients with a score of 0 compared to patients with a score of 8 points in both databases. ConclusionThe CHA2DS2-VASc score can identify AF patient subgroups with lower baseline eGFR and a higher risk of CKD progression, which has important implications for the management of anticoagulation in these patients.

Acute Kidney Injury to Chronic Kidney Disease Transition.

Acute kidney injury (AKI), even if followed by renal recovery, is a risk factor for the future development of chronic kidney disease (CKD) and end-stage renal disease (ESRD). In the previous years, novel insights in the pathophysiology of CKD progression suggested a causal link between AKI and CKD due to a maladaptive repair after severe and repeated injury. Several pathological mechanisms have been proposed to contribute to the progression of AKI and transition to CKD/ESRD including hypoxia and microvascular rarefaction, alterations of renal resident cell phenotypes and functions, cell cycle arrest in the G2/M phase, persistent chronic inflammation, and development of interstitial fibrosis, mitochondrial fragmentation, epigenetic changes, activation of renin-angiotensin system (RAS), cell and tissue senescence. Furthermore, several clinical factors have been identified such as severity of AKI, age, and comorbidities. The identification of AKI-to-CKD biomarkers could improve the early identification of AKI patients with higher risk for CKD progression. However, although our understanding in the pathophysiology of AKI-to-CKD transition is significantly improved, no novel intervention has been validated. Potential therapeutic approaches to treat AKI and block the transition to CKD/ESRD have been recently reported, but they need further validations. Key Messages: Maladaptive repair after AKI is strongly associated to the development of CKD and long-term consequences. The prompt identification of patients at higher risk for late CKD progression and the development of new therapeutic interventions remain critical research goals.

Association of Serum Soluble Urokinase Receptor Levels With Progression of Kidney Disease in Children

Conventional methods to diagnose and monitor chronic kidney disease (CKD) in children, such as creatinine level and cystatin C-derived estimated glomerular filtration rate (eGFR) and assessment of proteinuria in spot or timed urine samples, are of limited value in identifying patients at risk of progressive kidney function loss. Serum soluble urokinase receptor (suPAR) levels strongly predict incident CKD stage 3 in adults. To determine whether elevated suPAR levels are associated with renal disease progression in children with CKD. Post hoc analysis of 2 prospectively followed up pediatric CKD cohorts, ie, the ESCAPE Trial (1999-2007) and the 4C Study (2010-2016), with serum suPAR level measured at enrollment and longitudinal eGFR measured prospectively. In the 2 trials, a total of 898 children were observed at 30 (ESCAPE Trial; n = 256) and 55 (4C Study; n = 642) tertiary care hospitals in 13 European countries. Renal diagnoses included congenital anomalies of the kidneys and urinary tract (n = 637 [70.9%]), tubulointerstitial nephropathies (n = 92 [10.2%]), glomerulopathies (n = 69 [7.7%]), postischemic CKD (n = 42 [4.7%]), and other CKD (n = 58 [6.5%]). Total follow-up duration was up to 7.9 years, and median follow-up was 3.1 years. Analyses were conducted from October 2016 to December 2016. Serum suPAR level was measured at enrollment, and eGFR was measured every 2 months in the ESCAPE Trial and every 6 months in the 4C Study. The primary end point of CKD progression was a composite of 50% eGFR loss, eGFR less than 10 mL/min/1.73 m2, or initiation of renal replacement therapy. The primary end point in this study was renal survival, defined as a composite of 50% loss of GFR that persisted for at least 1 month, the start of renal replacement therapy, or an eGFR less than 10 mL/min/1.73 m2. Of the 898 included children, 560 (62.4%) were male, and the mean (SD) patient age at enrollment was 11.9 (3.5) years. The mean (SD) eGFR was 34 (16) mL/min/1.73 m2. The 5-year end point-free renal survival was 64.5% (95% CI, 57.4-71.7) in children with suPAR levels in the lowest quartile compared with 35.9% (95% CI, 28.7-43.0) in those in the highest quartile (P < .001). By multivariable analysis, the risk of attaining the end point was higher in children with glomerulopathies and increased with age, blood pressure, proteinuria, and lower eGFR at baseline. In patients with baseline eGFR greater than 40 mL/min/1.73 m2, higher log-transformed suPAR levels were associated with a higher risk of CKD progression after adjustment for traditional risk factors (hazard ratio, 5.12; 95% CI, 1.56-16.7; P = .007). Patients with high suPAR levels were more likely to have progression of their kidney disease. Further studies should determine whether suPAR levels can identify children at risk for future CKD.

Metabolic acidosis is common and associates with disease progression in children with chronic kidney disease

Recent studies in adult chronic kidney disease (CKD) suggest that metabolic acidosis is associated with faster decline in estimated glomerular filtration rate (eGFR). Alkali therapies improve the course of kidney disease. Here we investigated the prevalence and determinants of abnormal serum bicarbonate values and whether metabolic acidosis may be deleterious to children with CKD. Associations between follow-up serum bicarbonate levels categorized as under 18, 18 to under 22, and 22 or more mmol/l and CKD outcomes in 704 children in the Cardiovascular Comorbidity in Children with CKD Study, a prospective cohort of pediatric patients with CKD stages 3-5, were studied. The eGFR and serum bicarbonate were measured every six months. At baseline, the median eGFR was 27ml/min/1.73m2 and median serum bicarbonate level 21mmol/l. During a median follow-up of 3.3 years, the prevalence of metabolic acidosis (serum bicarbonate under 22 mmol/l) was 43%, 60%, and 45% in CKDstages 3, 4, and5, respectively. In multivariable analysis, the presence of metabolic acidosis as a time-varying covariate was significantly associated with log serum parathyroid hormone through the entire follow-up, but no association with longitudinal growth was found. A total of 211 patients reached the composite endpoint (ESRD or 50% decline ineGFR). In a multivariable Cox model, children with time-varying serum bicarbonate under 18 mmol/l had a significantly higher risk of CKD progression compared to those with a serum bicarbonate of 22 or more mmol/l (adjusted hazard ratio 2.44; 95% confidence interval 1.43-4.15). Thus, metabolic acidosis is a common complication in pediatric patients with CKD and may be arisk factor for secondary hyperparathyroidism and kidney disease progression.

Association of Urine Dipstick Proteinuria and Postoperative Renal Function Following Robotic Partial Nephrectomy.

In patients with normal estimated renal function before robot-assisted partial nephrectomy (RPN), there is still a risk for de Novo chronic kidney disease (CKD). We assessed the role of dipstick spot proteinuria in risk stratifying patients for CKD progression. From our prospectively maintained, institutional review board-approved database of patients undergoing RPN, we queried those with estimated glomerular filtration rate (eGFR) >60 and bilateral functional units. We assessed proteinuria through dipstick (trace or above) on voided urine in preoperative urologic appointment <3 weeks before RPN. Proteinuric patients were compared with the remainder of the cohort with parametric comparisons for continuous and chi-squared analysis for categoric variables. Multivariate logistic regression analyses were performed assessing the risk of de Novo CKD stage III development, estimated by the CKD-EPI equation. We found 269 patients with eGFR >60 preoperatively, of whom 57 (21%) had proteinuria preoperatively. In univariate analysis, these patients were more likely to be diabetic (p = 0.023) and to be on an angiotensin converting enzyme inhibitor or angiotensin receptor blocker (p = 0.001) but had similar age (p = 0.13), body mass index (p = 0.09), and tumor size (p = 0.56) with similar rates of hypertension (p = 0.07). At a median 16 months, controlling for confounding variables, preoperative proteinuria on urinary dipstick was associated with a 2.3× (95% confidence interval 1.03-4.95) increased risk of de Novo CKD stage III progression. Patients with proteinuria preoperatively, despite a normal eGFR, likely have intrinsic medicorenal disease. These patients should be counseled preoperatively that they have a higher risk of CKD progression following RPN.

A prospective clinical trial of specialist renal nursing in the primary care setting to prevent progression of chronic kidney: a quality improvement report.

BackgroundEarly detection and effective management of risk factors can potentially delay progression of chronic kidney disease (CKD) to end-stage kidney disease, and decrease mortality and morbidity from cardiovascular (CV) disease. We evaluated a specialist nurse-led intervention in the primary care setting to address accepted risk factors in a study sample of adults at ‘high risk of CKD progression’, defined as uncontrolled type II diabetes and/or hypertension and a history of poor clinic attendance.MethodsThe study was a non-controlled quality improvement study with pre- and post- intervention comparisons to test feasibility and potential effectiveness. Patients within two primary care practices were screened and recruited to the study. Fifty-two patients were enrolled, with 36 completing 12-months follow-up. The intervention involved a series of sessions led by the nephrology Nurse Practitioner with assistance from practice nurses. These sessions included assessment, education and planned medication and lifestyle changes. The primary outcome measured was proteinuria (ACR), and the secondary outcomes estimated glomerular filtration rate (eGFR) and 5-year absolute CV risk. Several ‘intermediary’ secondary outcomes were also measured including: blood pressure, serum total cholesterol, glycosylated haemoglobin (HbA1c), body mass index (BMI), prevalence of active smoking, a variety of self-management domains, and medication prescription. Analysis of data was performed using linear and logistic regression as appropriate.ResultsThere was a significant improvement in ACR (average decrease of −6.75 mg/mmol per month) over the course of the study. There was a small but significant decrease in eGFR and a reduction in 5 year absolute CV risk. Blood pressure, serum total cholesterol, and HbA1c all decreased significantly. Adherence to lifestyle advice improved with a significant reduction in prevalence of active smoking, although there was no significant change in BMI. Self-management significantly improved across all relevant domains.ConclusionsThe results suggest that a collaborative model of care between specialist renal nurses and primary care clinicians may improve the management of risk factors for progression of CKD and CV death. Further larger, controlled studies are warranted to definitively determine the effectiveness and costs of this intervention.Trial registrationAustralian and New Zealand Clinical Trials Registry number: ACTRN12613000791730Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2296-15-155) contains supplementary material, which is available to authorized users.

Dietary Acid Intake and Kidney Disease Progression in the Elderly

Background/Aims: Non-volatile acid is produced by metabolism of organic sulfur in dietary protein, and promotes kidney damage. We investigated the role of dietary acid load, in terms of net endogenous acid production (NEAP), in chronic kidney disease (CKD) progression. Methods: 217 CKD patients on low-protein diet with a normal serum bicarbonate level were enrolled in this retrospective cohort study in Japan. The primary outcome was 25% decline in estimated glomerular filtration rate (eGFR) or start of dialysis. Their NEAP was measured every 3 months. The patients were categorized into four groups on the basis of quartiles of NEAP every 3 months. The groups were treated as time-dependent variables. Results: The average age (SD) was 70.6 (7.1) years; eGFR 23.5 (14.2) ml/min/1.73 m². Analysis using extended Cox models for the NEAP groups adjusted for baseline characteristics (referring to group 1 showing the lowest NEAP) showed that high NEAP was associated with a high risk of CKD progression; group 2, adjusted hazard ratio (HR) 3.930 (95% confidence interval (CI) 1.914, 8.072); group 3, adjusted HR 4.740 (95% CI 2.196, 10.288); group 4, adjusted HR 4.303 (95% CI 2.103, 8.805). Logistic regression analysis adjusted for baseline characteristics showed that the occurrence of hypoalbuminemia or hyperkalemia was associated with low serum bicarbonate level and the presence of complications at baseline, but not with NEAP. Conclusion: In elderly CKD patients, our findings suggest that high NEAP is independently associated with CKD progression. The decrease in NEAP may be an effective kidney-protective therapy.

PP55 Socioeconomic Status and Chronic Kidney Disease: Further Findings from the Health Surveys for England 2009 and 2010

BackgroundRenal replacement therapy rates are higher in more deprived populations in developed countries. The relationship between population-level prevalence of chronic kidney disease (CKD) and socio-economic status (SES) is less clear....

High serum bicarbonate level within the normal range prevents the progression of chronic kidney disease in elderly chronic kidney disease patients

BackgroundMetabolic acidosis leads to chronic kidney disease (CKD) progression. The guidelines recommend a lower limit of serum bicarbonate level, but no upper limit. For serum bicarbonate level to be clinically useful as a therapeutic target marker, it is necessary to investigate the target serum bicarbonate level within the normal range to prevent CKD progression.MethodsOne hundred and thirteen elderly CKD patients, whose serum bicarbonate level was controlled within the normal range, were enrolled in this retrospective cohort study in Ibaraki, Japan. Outcome was defined as a decrease of 25% or more in estimated glomerular filtration rate (eGFR) or starting dialysis. We used Cox proportional hazard models adjusted for patients’ characteristics to examine the association between serum bicarbonate level and the outcome.ResultsFemale patients were 36.3%: average age (SD), 70.4 (6.6) years; eGFR, 25.7 (13.6) ml/min/1.73 m2; serum bicarbonate level, 27.4 (3.2) mEq/l. Patients with the lowest quartile of serum bicarbonate levels [23.4 (1.8) mEq/l] showed a high risk of CKD progression compared with patients with high serum bicarbonate levels [28.8 (2.3) mEq/l]: adjusted hazard ratio (HR), 3.511 (95% CI, 1.342-9.186). A 1 mEq/l increase in serum bicarbonate level was associated with a low risk of CKD progression: adjusted HR, 0.791 [95% confidence interval (CI), 0.684-0.914].ConclusionsIn elderly CKD patients, our findings suggest that serum bicarbonate level is independently associated with CKD progression, and that a high serum bicarbonate level is associated with a low risk of CKD progression. A high target serum bicarbonate level within the normal range may be effective for preventing CKD progression.

Cross-sectional survey of the prevalence of reduced estimated glomerular filtration rate, albuminuria and cardiovascular risk in a native Spanish population

HERMEX is a population-based study which tries to evaluate the relative weight of cardiovascular risk factors in inhabitants of Extremadura, Spain. This report presents the data about chronic kidney disease (CKD) in a Spanish population sample. For an observational cross-sectional population-based study, 3,402 subjects were randomly selected from health care system records. The final sample included 2,813 participants (mean age 51.2 years, 53.5% women). Renal function was estimated from serum creatinine using the 4-variable Modification of Diet in Renal Disease (MDRD-4) Study and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations. Individual renal risk was calculated using the Kidney Disease Improving Global Outcomes (KDIGO) table. Using the CKD-EPI formula, 3.6% of participants had a glomerular filtration rate (GFR) <60 ml/min. MDRD-4 gave a result of 4.0%. Prevalence of albuminuria was 5.5%. Taken together, in patients with albuminuria and/or reduced GFR, the prevalence of renal disease was 8.1%. The KDIGO renal risk table suggested that 0.05% of patients were at high or very high risk of CKD progression and 1.6% at medium risk. CKD was more common in those who were obese, hypertensive, dyslipidemic or had diabetes. Multivariate analysis showed an independent negative association of CKD as dependent variable with systolic blood pressure and body mass index, but a positive correlation with diastolic blood pressure and male sex. A low frequency of abnormal GFR was detected in a randomly selected sample of the Spanish general population. This finding agreed with the low rates of cardiovascular mortality and morbidity observed in Spain in spite of a high prevalence of classic cardiovascular risk factors.

The severity of acute kidney injury predicts progression to chronic kidney disease

Acute kidney injury (AKI) is associated with progression to advanced chronic kidney disease (CKD). We tested whether patients who survive AKI and are at higher risk for CKD progression can be identified during their hospital admission, thus providing opportunities to intervene. This was assessed in patients in the Department of Veterans Affairs Healthcare System hospitalized with a primary diagnosis indicating AKI (ICD9 codes 584.xx). In the exploratory phase, three multivariate prediction models for progression to stage 4 CKD were developed. In the confirmatory phase, the models were validated in 11,589 patients admitted for myocardial infarction or pneumonia during the same time frame that had RIFLE codes R, I, or F and complete data for all predictor variables. Of the 5351 patients in the AKI group, 728 entered stage 4 CKD after hospitalization. Models 1, 2, and 3 were all significant with ‘c' statistics of 0.82, 0.81, and 0.77, respectively. In model validation, all three were highly significant when tested in the confirmatory patients, with moderate to large effect sizes and good predictive accuracy (‘c' 0.81–0.82). Patients with AKI who required dialysis and then recovered were at especially high risk for progression to CKD. Hence, the severity of AKI is a robust predictor of progression to CKD.