Initial Glomerular Filtration Rate Research Articles

Clinical Value of Complement Activation Biomarkers in Overt Diabetic Nephropathy

BackgroundExperimental studies support a role of complement activation in diabetic nephropathy (DN), yet few clinical correlates exist. We evaluated urinary levels of sC5b-9 membrane attack complex (MAC) in patients with overt DN, and examined its association with the glomerular filtration rate (GFR) decline, proteinuria, and inflammatory biomarkers. We explored different complement pathways and compared our findings to autoimmune glomerulonephritis.MethodsWe prospectively followed 83 patients with DN and obtained repeated measurements of proteinuria, complement fragments (sC5b-9, C4a, C1q, mannose-binding lectin–associated serine protease [MASP]-1, and factor Bb), monocyte chemoattractant protein-1 (MCP-1), and transforming growth factor (TGF)-β1. We assessed independence and interactions using general linear models and repeated measures analyses and compared levels with subjects with active focal and segmental glomerulosclerosis, ANCA-associated vasculitis, and membranous and IgA nephropathies (n = 63).ResultsThe diabetic cohort had an initial GFR of 25 ± 9 ml/min per 1.73 m2 and a renal function decline of 2.9 ± 3.0 ml/min per 1.73 m2 per year. All complement biomarkers were strongly intercorrelated and associated with biomarker inflammation and fibrosis, proteinuria, and the rate of renal function decline. There was a significant interaction (P = 0.03) between the level of proteinuria and urinary sC5b-9: in individuals with higher levels of urinary MAC, the relationship between proteinuria and the rate of renal function decline was more pronounced than in those with low urinary MAC. Finally, patients with DN had levels of urinary sC5b-9 comparable to autoimmune glomerulonephritis, when stratified by the level of proteinuria.ConclusionUrinary MAC is present in patients with overt DN at levels comparable to autoimmune glomerulonephritis and correlates with the GFR decline, supporting that complement activation and its measurement are clinically relevant in DN.

Estimating the Change in Renal Function During the First Year of Therapy in ANCA-Associated Vasculitis

IntroductionStudies in antineutrophil cytoplasmic autoantibody (ANCA)–associated vasculitis (AAV) consistently show that the months following diagnosis have the greatest impact on the long-term renal function. Yet, it remains uncertain how much early gain should be expected with treatment. We sought to determine the factors associated with the change in glomerular filtration rate (GFR) throughout the first year.MethodsWe retrospectively reviewed patients from 3 university hospitals who received treatments. We assessed the proportions of glomeruli with crescents, with global sclerosis, the AAV glomerulonephritis classification, the severity of chronic vascular and tubulo-interstitial disease, and the presence of acute tubular injury (ATI). We used repeated-measures analyses of variance (ANOVAs) to determine factors associated with the change in GFR throughout the first year.ResultsThere were 162 individuals with AAV identified, 96 with a valid renal biopsy and 82 with at least 12 months of follow-up. The initial GFR of 30 ± 25 ml/min per 1.73 m2 rose by 15 ± 20 during the first year. The severity of pathology findings, myeloperoxidase positivity, and those with kidney- and lung-limited disease presented with a lower GFR. Younger patients with a lower initial GFR and the presence of ATI correlated with a greater increase in GFR by 12 months. A higher proportion of crescents did not predict the change in GFR, contrary to global glomerulosclerosis, where each 10% increase added a loss of 2.7 ± 1.3 ml/min per 1.73 m2 per year (P = 0.03). These factors remained independent of each other.ConclusionMultiple factors influence renal recovery during the first year of therapy. Estimating the change in GFR early on will help identify and reassess outliers.

Short- and long-term follow-up of living kidney donors

Living-donor kidney transplantation is a well-established treatment of end-stage renal disease in Tunisia. Over the years, concerns have increased about the harmlessness of kidney donation. This longitudinal single center study was carried out to evaluate the safety of nephrectomy as well as further medical and surgical outcomes among donors. We collected and analyzed clinical, biological, biochemical and kidney size data at the time of nephrectomy and at M1, M3, M6, Y1, Y2, and Y4 after donation measured by ultrasound. All donor nephrectomies performed in the nephrology and transplantation unit of Sahloul Hospital of Sousse since October 2006 were included. Criteria of exclusion were lost to follow-up or lack of complete data. Of the 106 donors (66 females and 40 males), 92 donors were included in the follow-up analysis after following exclusion criteria. The mean age at the time of nephrectomy was 42.8 ± 10 years with the sex ratio 0.6. and 27% of our donors were mothers. Twenty-two percent of the donors were obese and 4% were hypertensive. The median initial glomerular filtration rate (GFR) was 105 mL/min/1.73 m2. The surgical approach was costal lumbotomy in 96% of cases and laparoscopy for four cases. The kidneys were removed from the left side in 93% of cases. Postoperative mortality was zero and early postoperative morbidity was low. The median duration of hospital stay was nine days. During follow-up, 14% attended all recommended visits. The median follow-up duration was 26 months. After two years post donation, the prevalence of HTN was 28% and obesity was 26%. The prevalence of GFR decline (50-59 mL/min) was 14% using formula by modification of diet in renal disease. None of our donors reached stage 4 or 5 CKD. Twelve had proteinuria and one donor had diabetes, a comparable prevalence of morbidities to the general population.

Delta Neutrophil Index is Useful to Predict Poor Outcomes in Male Patients with Alcoholic Ketoacidosis.

BackgroundAlcoholic ketoacidosis (AKA) is known as a benign disease, but the related mortality reported in Korea is high. Acidosis and alcohol change the immunity profile, and these changes can be identified early using the delta neutrophil index (DNI). We aimed to evaluate the use of DNI and other standard laboratory parameters as predictors of prognosis in AKA patients.MethodsOne hundred eighteen males with AKA were evaluated at the Wonju Severance Christian hospital between 2009 and 2014. We performed a retrospective analysis of demographic, clinical, and laboratory parameters data. Receiver operating characteristic curves (ROC) and multivariate Cox regression was used to identify renal survival and mortality.ResultsSurvival patients had lower initial DNI levels than non-survival patients (4.8±6.4 vs 11.4±12.5, p<0.001). In multivariate-adjusted Cox regression analysis, higher initial increased DNI (HR 1.044, 95% CI 1.003–1.086, p=0.035), and lower initial pH (HR 0.044, 95% CI 0.004–0.452, p=0.008) were risk factors for dialysis during hospitalization. Further, higher initial DNI level (HR 1.037; 95% CI 1.006-1.069; p=0.018), lower initial pH (HR 0.049; 95% CI 0.008–0.312; p=0.001) and lower initial glomerular filtration rate (GFR) (HR 0.981; 95% CI 0.964–0.999; p=0.033) were predictors of mortality. A DNI value of 4.5% was selected as the cut-off value for poor prognosis and Kaplan-Meier plots showed that AKA patients with an initial level DNI ≥4.5% had lower cumulative survival rates than AKA patients with an initial DNI <4.5%.ConclusionIncreased initial serum DNI levels may help to predict renal survival and prognosis in male AKA patients.

1929. Risk of Acute Kidney Injury in Combat-Injured Patients Associated With Concomitant Vancomycin and Extended-Spectrum β-Lactam Antibiotic Use

BackgroundStudies of vancomycin (VANC) and piperacillin–tazobactam (VPT) induced acute kidney injury (AKI) have included diverse populations obscuring clinical generalizations. To our knowledge, previous studies have omitted combat-related trauma patients despite frequent exposure to broad-spectrum antimicrobials. Our objective was to analyze whether combination therapy with VPT was associated with an increased risk of AKI compared with VANC and other broad-spectrum β-lactam antibiotics (VBL).MethodsPatients within the Trauma Infectious Disease Outcomes Study (TIDOS) who received ≥48 hours concomitant VPT or VBL started within 24 hours of each other were assessed. Exclusion criteria were receipt of renal replacement therapy and baseline creatinine >1.5 mg/dL or missing. Based on prior studies, AKI was defined by meeting any of the RIFLE, AKIN or Vanc Consensus Guidelines criteria 3–7 days after therapy initiation. Glomerular Filtration Rate (GFR) was calculated using Modification of Diet in Renal Disease (MDRD) equation.ResultsOf 2692 patients, 39 patients who received VPT and 197 who received VBL (172 meropenem, 17 imipenem-cilastatin, and 8 cefepime) were included with median ages of 25 and 24 years old, respectively. Initial median GFRs were 138mL/minute in both groups. Gender distribution was equal with 97% males receiving VPT and 99% VBL. Thirty-five (90%) patients in VPT and 186 (94%) in VBL had an Injury Severity Score>15 (P = 0.28). Median duration of VANC therapy was 6 and 8 days for VPT and VBL (P = 0.36). Injuries were sustained in Afghanistan in 82% treated with VPT and 92% with VBL (P = 0.06). The groups differed by US-based hospital (P = 0.06), and presence of blast injury which was more common in VBL (P < 0.001). In the VBL group, incidence of AKI was 9.1% compared with 12.8% in the VPT group (P = 0.55). Median time to AKI was 6 days (IQR 5–6) for those receiving VPT and 4 days (IQR 3–6) for VBL.ConclusionRecent reports of nephrotoxicity of VPT have been challenging to interpret due to multiple potential confounders. In this young and previously healthy severely ill combat-injured population, VPT was not associated with higher crude rates of AKI than VBL. This may be related to this unique patient population or sample size.Disclosures All authors: No reported disclosures.

The role of intraoperative parameters on predicting laparoscopic abdominal surgery associated acute kidney injury

BackgroundLaparoscopic abdominal surgery has been widely used to reduce the length of hospital stay and complications from open abdominal surgery. During the operation, the creation of pneumoperitoneum is used for better visualization of the operating field. However, the effect of pneumoperitoneum on kidney function is unknown. We aimed to identify risk factors and predictors associated with AKI development following laparoscopic abdominal surgery.MethodsA single-center prospective cohort study of laparoscopic abdominal surgery patients between June 2012 and December 2013. Acute kidney injury (AKI) was identified by Kidney Disease Improving Global Outcome (KDIGO) criteria. Urinary neutrophil gelatinase associated lipocalin (uNGAL) was measured on the first 3 days after surgery as a surrogate marker of AKI.ResultsOf the 64 patients, 23 (35%) developed postoperative AKI. The mean age, initial blood pressure, and initial glomerular filtration rate were not different between AKI and non-AKI groups. Inflation time and exposure index were significantly higher in the AKI group compared to non-AKI group (192.0 vs 151.1 min, p = 0.045, and 2325.9 vs 1866.1 mmHg-minutes, p = 0.035). Operation time, mean intra-abdominal pressure, duration of intraoperative hypotension, amount of blood loss and intravenous fluid were not different between groups. In multivariable analysis adjusted for age, diabetes, baseline estimated glomerular filtration rate, and type of operation (urological surgery), exposure index was significantly associated with postoperative AKI, with odds ratio (95% CI) 1.47 (1.05–2.04), p = 0.024. By combining the intraoperative parameters with clinical model the area under the receiver operating characteristic curve was 0.71 (95% CI 0.58–0.84).ConclusionsAKI was a common condition in laparoscopic abdominal surgery. Exposure index has been proposed as a novel predictor of laparoscopic abdominal surgery associated AKI.

Complement activation is associated with more severe course of diarrhea-associated hemolytic uremic syndrome, a preliminary study.

Diarrhea-associated hemolytic uremic syndrome is characterized by hemolytic anemia, thrombocytopenia, and acute kidney injury secondary to enteric infection, typically Shiga toxin-producing Escherichia coli. Shiga toxin 2 is able to activate alternative complement pathways; therefore, the aim of the study was to analyze C3 as a predictor of clinical courses in patients with diarrhea-associated hemolytic uremic syndrome. We hypothesized that the patients with increased complement activation at admission suffered from a more severe course. We retrospectively analyzed data of 33 pediatric patients between 1999 and 2015 in the Czech Republic. We tested the association of a C3 concentration with biochemical parameters and the clinical data reflecting the severity of the disease. We found significant correlation between the initial C3 and the duration of renal replacement therapy (r = - 0.62, p = 0.0001) and the initial glomerular filtration rate (r = 0.36, p = 0.026). Patients with C3 < 0.825g/L needed renal replacement therapy and also had significantly more renal complications (p = 0.015).Conclusion: Based on our study, decreased C3 concentrations can be used as one of the risk factors that can help predict the need for acute dialysis and a more severe course of disease in children with diarrhea-associated hemolytic uremic syndrome. What is Known: • Shiga toxin modulates the function of complement regulatory proteins and thus contributes to complement activation in patients with diarrhea-associated hemolytic uremic syndrome. • Risk factors that can predict the need for acute renal replacement therapy and poor outcome in patients with diarrhea-associated hemolytic uremic syndrome are mainly the combination of oligoanuria, dehydration, leukocytosis, high hematocrit > 23%, and neurological involvement. What is New: • A lowered concentration of C3 at the time of initial presentation of diarrhea-associated hemolytic uremic syndrome was associated with more severe renal failure and the need for renal replacement therapy along with the development of more extra renal complications. • Decreased C3 at admission can predict complicated course of diarrhea-associated hemolytic uremic syndrome.

Urinary Neutrophil Gelatinase-Associated Lipocalin as a Biomarker for Renal Injury in Liver Transplant Recipients Using Calcineurin Inhibitors

BackgroundUrinary neutrophil gelatinase-associated lipocalin (uNGAL) is an early biomarker of renal injury. We examined the feasibility of using uNGAL as an early predictor of renal impairment in patients under calcineurin inhibitors in liver transplant recipients. MethodsFrom urine samples obtained from liver transplant recipients, the glomerular filtration rate (GFR) at the time of urine sampling was compared with that at 5 to 7 months later. Patients were divided into 3 groups according to initial GFR and then divided into 2 groups according to the uNGAL level of 25 ng/mL. Progression of renal injury (PRI) was defined as a decrease in the GFR of more than 5 mL/min/1.73 m2 in the mild or moderate groups, or if a normal group patient shifted to the mild or moderate group. ResultsFifty-one patients were enrolled. The mean uNGAL level was higher in the moderate group than in the normal and mild groups (18.38 ± 14.31 vs 7.74 ± 8.13; P < .01). A proportion of uNGAL-high was also higher in the moderate group than in the mild group (40% vs 5%; P = .03). uNGAL-high was a risk factor for 6-month PRI (odds ratio, 60.375; 95% confidence interval, 1.283–4088.25; P = .037) and 1-year PRI (odds ratio, 21.311; % confidence interval, 0.947–479.578; P = .054). ConclusionsA uNGAL of >25 ng/mg can be a marker for moderate renal impairment (GFR of 30–59 mL/min/1.73 m2) and a predictor of PRI at 6 months in patients using calcineurin inhibitors. Renal protection strategies should be considered in liver transplant recipients with a uNGAL of >25 ng/mg in spot urine sampling.

Development and validation of Women Acute Myocardial Infarction in-Hospital Mortality Score (WAMI Score)

BackgroundA variety of risk models have been developed to predict acute myocardial infarction (AMI) in-hospital mortality risk. As a distinct, higher-risk population, women with AMI have different risk profiles from their men counterparts. Published researches have indicated that the interaction between variables in these models for in-hospital mortality and gender are significant. Due to the interaction and gender differences, the predicting value of these risk models for women could be controversial. MethodsDatabases from the China Patient-centered Evaluative Assessment of Cardiac Events (China PEACE) Retrospective AMI Study were utilized for model derivation (n=16,100, women were 4896) and databases from the China PEACE Prospective AMI Study for model validation (n=6207, women were 2090). A multivariable backward stepwise logistic regression was used to examine correlates of in-hospital mortality, and the variables were subsequently weighted and integrated into a scoring system. ResultsWe constructed a novel risk-predicting tool to estimate the baseline risk of in-hospital mortality among women with AMI. The risk score includes 8 variables [age, systolic blood pressure, heart rate, initial glomerular filtration rate (GFR), serum glucose, Killip class, cardiac arrest, ventricular tachycardia/ventricular fibrillation (VT/VF)]. The prognostic discriminatory capacity of the Women Acute Myocardial Infarction in-Hospital Mortality (WAMI) risk score was excellent (c statistic 0.84, 95% confidence interval [CI]: 0.83 to 0.86, p<0.001). External validation of the model showed better prognostic capacity (c statistic 0.87, 95% CI: 0.84 to 0.90, p<0.001) than the GRACE risk score (0.77, 95% CI 0.72–0.82, p<0.001) and TIMI risk score (0.72, 95% CI 0.68–0.77, p<0.001). ConclusionsThe WAMI Score is a simple robust tool for predicting the in-hospital mortality risk of women with AMI. Trial registration“China PEACE-Retrospective AMI Study”, NCT01624883, retrospectively registered: April 2012. Date of enrolment of the first participant to the trial: June 17, 2012.“China PEACE-Prospective AMI Study”, NCT01624909, prospectively registered: December 2012. Date of enrolment of the first participant to the trial: June 17, 2012.

Predictors of acute kidney injury in patients admitted with ST-elevation myocardial infarction - results from the Bremen STEMI-Registry.

Deterioration of renal function after exposition to contrast media is a common problem in patients with myocardial infarction undergoing percutaneous coronary interventions. The aim of the present study was to assess the incidence of acute kidney injury in patients admitted with ST-elevation-myocardial infarction (STEMI) and its association with infarction severity, comorbidities and treatment modalities, including amount of contrast media applied. All patients with STEMI from the metropolitan area of Bremen, Germany are treated at the Bremen Heart Centre and since 2006 documented in the Bremen STEMI-Registry. Acute kidney injury was graded from stage 0 to 3 following the Kidney-disease-improving-global outcomes criteria from 2012. Data from 3810 patients admitted with STEMI were included in this study. No acute kidney injury was observed in 3120 (82%) patients while acute kidney injury was detected in 690 (18%) patients: Stage 1: n=497 (13%), 2: n=66 (2%), 3: n=127 (3%). Acute kidney injury was associated with elevated 30-day (0: 3%, 1: 20%, 2: 46%, 3: 58%) and one-year mortality rates (0: 6%, 1: 26%, 2: 49%, 3: 66%). Higher acute kidney injury stages were associated with higher peak creatine kinase (in U/l±SEM): stage 0: 1748±33, 1: 2588±127, 2: 3684±395, 3: 3330±399, p (<0.01), lower mean systolic blood pressure at admission (in mmHG±SD): 0: 133±28, 1: 129±31; 2: 121±31, 3: 115±33 ( p<0.01) and higher Thrombolysis in Myocardial Infarction risk score for STEMI (scale 0-14±SD): 0: 2.71±2, 1: 4.08±2, 2: 4.98±2, 3: 5.05±2, ( p<0.01). However, no such association could be found between acute kidney injury stage and amount of contrast media applied (in ml±SD) 0: 138±57, 1: 139±61; 2: 140±76; 3: 145±80 ( p=0.5). Reduced initial glomerular filtration rate was associated with higher incidences of acute kidney injury while again no relation to amount of contrast media could be observed in subgroups ranked by initial glomerular filtration rate. A multivariate analysis confirmed these results: while left-heart-failure/cardiogenic shock (odds ratio (OR) 4.2, 95% confidence interval (CI) 3.3-5.5) as well as larger infarctions (peak creatine kinase >3000 U/l (OR 2.2, 95% CI 1.7-2.8)) were independently associated with a greater risk for acute kidney injury, amount of contrast media applied during angiography was not (150-250 ml, OR 0.95, 95% CI 0.8-1.2 ( p=0.7), >250 ml, OR 1.3, 95% CI 0.8-2.0 ( p=0.5)). Acute kidney injury, which was associated with elevated short- and long-term mortality rates, could be observed in 18% of patients admitted with STEMI. The present data suggest that severity and haemodynamic impairment due to STEMI rather than contrast-media-induced nephropathy is the key contributor for acute kidney injury in STEMI patients. The deleterious effect of the myocardial infarction itself on renal function can be explained through renal hypoperfusion, neurohormonal activation or other pathomechanisms that might have been underestimated in the past.

Determinants of decline of renal function in treated hypertensive patients: the Campania Salute Network.

Hypertension is a leading cause of chronic kidney disease (CKD) and a decrease in glomerular filtration rate (GFR) is associated with a higher prevalence of hypertension and an increased proportion of suboptimal blood pressure (BP) control. To investigate characteristics associated with GFR decline, we selected 4539 hypertensive patients from the Campania Salute Network (mean age 53 ± 11 years) with at least 3 years of follow-up (FU) and no more than Stage III CKD. GFR was calculated at baseline and at the last available visit using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. GFR decline was defined as a ≥30% decrease from initial GFR for patients in Stage III CKD or by a composite ≥30% decrease from baseline and a final value of <60 for those < with Stage III or higher CKD. At a mean FU of 7.5 years, 432 patients (10%) presented with GFR decline. Those patients were older, more likely to be diabetic, with lower GFR and ejection fraction, higher systolic and lower diastolic BP and higher left ventricular (LV) mass and relative wall thickness at baseline; during FU, patients with GFR decline exhibited higher systolic BP, took more drugs and developed more atrial fibrillation (all P < 0.02). The probability of GFR decline was independently associated with older age, prevalent diabetes, baseline lower GFR, higher systolic BP during FU, FU duration, increased LV mass and incident AF with no impact from antihypertensive and antiplatelet medications. During antihypertensive therapy, kidney function declines in patients with initially lower GFR, increased LV mass and suboptimal BP control during FU.

Effects of staged versus ad hoc percutaneous coronary interventions on renal function-Is there a benefit to staging?

The purpose of this study is to determine whether ad hoc (same session) percutaneous coronary intervention, and staged (multiple session) percutaneous coronary intervention (PCI) have different renal outcomes. This is a retrospective cohort study that compares the maximal decline in glomerular filtration rate (GFR) at various times points (3-6days, 1-4weeks, 4-12weeks) after either ad hoc or staged PCI. 115 patients undergoing staged PCI and 115 matched ad hoc PCI controls were included in the study. They were equivalent in baseline GFR, left ventricular ejection fraction and intra-procedural volume status based on LVEDP. The group undergoing staged PCI had greater cumulative fluoroscopy time, SYNTAX score and number of stents placed. Staged PCIs used less contrast per catheterization (155.0±5.6mL) but higher cumulative contrast dose (326.6±14.0mL) compared to ad hoc PCIs (193.4±7.2mL). Following intervention, there was a progressive decline in renal function that did not significantly differ between the ad hoc and staged groups. In the subgroup of patients with initial GFR ≤60cm3/min, staged PCI was associated with 2.6-fold greater decline in renal function 4-12weeks after the procedure compared to ad hoc. A propensity match analysis performed in patients with GFR ≤60cm3/min confirmed worse renal function in the staged group at 4-12weeks. Staged PCI exposes patients to greater cumulative contrast agent loads. The decline in renal function observed in both groups did not differ significantly, however worse renal outcomes were observed in the staged PCI group with baseline GFR ≤60cm3/min.

Anti-neutrophil cytoplasmic antibody-associated vasculitis with renal involvement: Analysis of 89 cases

IntroductionThe anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis with renal involvement are associated with high morbi-mortality. In this study we analyse if the prognosis of these diseases have improved in recent years, and which factors influence the outcomes. Material and methodsRetrospective single-centre observational study, which included all patients diagnosed with microscopic polyangiitis and granulomatosis with polyangiitis with renal involvement in the last 25 years. Demographic, clinical and biochemical parameters of prognostic interest were recorded. The differences between four chronological periods were analysed, along with the determinants of a poor outcome (death or end-stage renal disease). ResultsEighty-nine patients were included (mean age 64±15 years). Sixty-four patients (72%) had microscopic polyangiitis and 25 (28%) granulomatosis with polyangiitis.During the study period, 37 (42%) patients died. Through Cox regression analysis, the best determinants of mortality were the initial glomerular filtration rate (HR 0.911; p=0.003), Charlson comorbidity index (HR 1.513; p<0.0001) and tobacco smoking (HR 1.816; p=0.003).35% developed end-stage renal disease, and the best determinants (by competing-risk regression) were: initial glomerular filtration rate (sub-hazard ratio [SHR]: 0.791; p<0.0001), proteinuria (SHR: 1.313; p<0.0001), and smoking status (SHR: 1.848; p=0.023).No differences were found in patients’ mortality or renal survival between the different study periods. ConclusionsPrognosis of anti-neutrophil cytoplasm antibodies vasculitis with renal involvement treated with conventional immunosuppressive therapy remains unsatisfactory, and continues to have increased long-term complications and mortality.

Vasculitis asociada a anticuerpos contra el citoplasma de neutrófilo con afectación renal: análisis de 89 casos

IntroductionThe anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis with renal involvement are associated with high morbi-mortality. In this study we analyse if the prognosis of these diseases have improved in recent years, and which factors influence the outcomes. Material and methodsRetrospective single-centre observational study, which included all patients diagnosed with microscopic polyangiitis and granulomatosis with polyangiitis with renal involvement in the last 25 years. Demographic, clinical and biochemical parameters of prognostic interest were recorded. The differences between four chronological periods were analysed, along with the determinants of a poor outcome (death or end-stage renal disease). ResultsEighty-nine patients were included (mean age 64±15 years). Sixty-four patients (72%) had microscopic polyangiitis and 25 (28%) granulomatosis with polyangiitis.During the study period, 37 (42%) patients died. Through Cox regression analysis, the best determinants of mortality were the initial glomerular filtration rate (HR 0.911; P=.003), Charlson comorbidity index (HR 1.513; P<.0001) and tobacco smoking (HR 1.816; P=.003).35% developed end-stage renal disease, and the best determinants (by competing-risk regression) were: initial glomerular filtration rate (sub-hazard ratio [SHR]: 0.791; P<.0001), proteinuria (SHR: 1.313; P<.0001), and smoking status (SHR: 1.848; P=.023).No differences were found in patients’ mortality or renal survival between the different study periods. ConclusionsPrognosis of anti-neutrophil cytoplasm antibodies vasculitis with renal involvement treated with conventional immunosuppressive therapy remains unsatisfactory, and continues to have increased long-term complications and mortality.

Predictors of mortality in children with lupus nephritis

Background Renal involvement during the clinical course ofsystemic lupus erythematosus (SLE) is generally considered to bethe most important factor influencing disease prognosis in termsof morbidity and mortality. Various factors have been reported toinfluence the prognosis of lupus nephritis (LN).Objective To analyze clinical signs and laboratory parameters thatmight serve as predictors associated with mortality in pediatricLN.Methods Retrospectively, medical records of children with LNat Soetomo Hospital from 1998 to 2011 were studied. Diagnosisof SLE was based on Revised American Rheumatism Associationcritera, while patients with clinical manifestations of hypertension,abnormal urinalysis, and serum creatinin &gt; 1 mg/dL wereconsidered as lupus nephritis. Cox proportional hazard modelingwas used to assess for associations of clinical signs and laboratoryparameters with mortality. Kaplan-Meier survival analysis wasused to assess the cumulative survival from the time of diagnosisto the outcome.Results There were 57 children with LN of whom 43 (75%) weregirls. The female-to-male ratio was 3:1. Subjects’ mean age was 10.6(SD 6.87) years. The mean time of observation was 51 (SD 74.54)months and 23 (40%) children died. Age, gender, hypertension,hematuria, proteinuria, and anemia were not significant aspredictors for mortality. However, hypertensive crisis (HR=2.79;95%CI 1.16 to 6.75; P=0.02) and initial glomerular filtration rate(GFR) of &lt;75 mL/min/1.73m2 (HR=3.01; 95%CI 1.23 to 7.34;P=0.01) were significant predictors of mortality in children with LN.The mean survival time of LN with hypertensive crisis and initialGFR &lt;75 mL/min/1.73m2 was 36.9 (SD 12.17) months.Conclusion Hypertensive crisis and GFR &lt;75 mL/min/1.73m2 aresignificant predictors of mortality in children with LN.

Predictors of mortality in children with lupus nephritis

Background Renal involvement during the clinical course ofsystemic lupus erythematosus (SLE) is generally considered to bethe most important factor influencing disease prognosis in termsof morbidity and mortality. Various factors have been reported toinfluence the prognosis of lupus nephritis (LN).Objective To analyze clinical signs and laboratory parameters thatmight serve as predictors associated with mortality in pediatricLN.Methods Retrospectively, medical records of children with LNat Soetomo Hospital from 1998 to 2011 were studied. Diagnosisof SLE was based on Revised American Rheumatism Associationcritera, while patients with clinical manifestations of hypertension,abnormal urinalysis, and serum creatinin > 1 mg/dL wereconsidered as lupus nephritis. Cox proportional hazard modelingwas used to assess for associations of clinical signs and laboratoryparameters with mortality. Kaplan-Meier survival analysis wasused to assess the cumulative survival from the time of diagnosisto the outcome.Results There were 57 children with LN of whom 43 (75%) weregirls. The female-to-male ratio was 3:1. Subjects’ mean age was 10.6(SD 6.87) years. The mean time of observation was 51 (SD 74.54)months and 23 (40%) children died. Age, gender, hypertension,hematuria, proteinuria, and anemia were not significant aspredictors for mortality. However, hypertensive crisis (HR=2.79;95%CI 1.16 to 6.75; P=0.02) and initial glomerular filtration rate(GFR) of <75 mL/min/1.73m2 (HR=3.01; 95%CI 1.23 to 7.34;P=0.01) were significant predictors of mortality in children with LN.The mean survival time of LN with hypertensive crisis and initialGFR <75 mL/min/1.73m2 was 36.9 (SD 12.17) months.Conclusion Hypertensive crisis and GFR <75 mL/min/1.73m2 aresignificant predictors of mortality in children with LN.

Colistin nephrotoxicity increases with age.

Colistin (COL) has become the backbone of the treatment of infections due to extensively drug-resistant (XDR) Gram-negative bacteria. The most common restriction to its use is acute kidney injury (AKI). We conducted a retrospective cohort study to evaluate risk factors for new-onset AKI in patients receiving COL. The cohort consisted of 198 adults admitted to 9 referral hospitals between January 2010 and October 2012 and treated with intravenous COL for ≥ 72 h. Patients with no pre-existing kidney dysfunction were compared in terms of risk factors and outcomes of AKI graded according to the RIFLE criteria. Logistic regression analysis was used to identify associated risk factors. A total of 198 patients met the inclusion criteria, of whom 167 had no pre-existing kidney dysfunction; the mean patient age was 58.77 (± 18.98) y. Bloodstream infections (34.8%) and ventilator-associated pneumonia (32.3%) were the 2 most common indications for COL use. New-onset AKI developed in 46.1% of the patients, graded as risk (10%), injury (15%), and failure (21%). Patients with high Charlson co-morbidity index (CCI) scores (p = 0.001) and comparatively low initial glomerular filtration rate (GFR) estimations (p < 0.001) were more likely to develop AKI, but older age (p = 0.001; odds ratio 5.199, 95% confidence interval 2.684-10.072) was the major predictor in the multivariate analysis. In-hospital recovery from AKI occurred in 58.1%, within a median of 7 days. COL-induced nephrotoxicity occurred significantly more often in patients older than 60 y of age and was related to low initial GFR estimations and high CCI scores, which were basically determined by age.

Posterior urethral valve: Prognostic factors and renal outcome.

Objective:The aim was to study the outcome of posterior urethral valve (PUV) cases treated by stepladder protocol and the prognostic factors affecting the outcome.Materials and Methods:Hospital records of all PUV patients treated by stepladder protocol between January 1992 and December 2013 were reviewed. The studied parameters were: Age at presentation, serum creatinine, types of surgical intervention, vesicoureteral reflux (VUR) on initial voiding cystourethrogram (VCUG), renal cortical scars, plasma renin activity (PRA), and glomerular filtration rate (GFR).Results:Of 396 PUV patients treated during the study period, 152 satisfied study criteria. The age at presentation ranged from 2 days to 15 years (mean 31.3 months). The mean follow-up period was 5 years (range: 2-18 years). Primary endoscopic valve ablation was the most common initial procedure. Chronic renal failure was seen in 42.7% patients at the last follow-up. Serum creatinine at presentation, initial PRA levels, initial GFR, and PRA levels at last follow-up were significant predictors of final renal outcome. Age at presentation (<1 vs. >1 year), presence/absence of VUR on initial VCUG and renal cortical scars had no significant correlation with ultimate renal function.Conclusion:Our study confirms the high prognostic significance of initial serum creatinine, PRA levels and GFR in cases with PUV. PRA also holds promise in long-term follow-up of these patients as a marker of progressive renal damage.

Initial glomerular filtration rate and survival in hemodialysis. The role of permanent vascular access.

A significant increase in the number of patients starting chronic hemodialysis (HD) with an estimated glomerular filtration rate (eGFR)≥10 mL/min/1.73 m(2) was observed in Argentina between 2004 and 2009. In order to study this topic, we calculated the mortality hazard ratios (HR) in a cohort of incident HD individuals from the Argentine Registry of Chronic Dialysis [Registro Argentino de Diálisis Crónica] (2004-2009), grouped according to the initial eGFR (0-4.9, 5-9.9, 10-14.9 and ≥15 mL/min/1.73 m(2) ; reference group 0-4.9) estimated by CKD-EPI; in three cohorts: "total population", "healthy" (<65 years, without diabetes or comorbidities) and "planned entry" (with permanent vascular access). After adjusting the population (n=16,931) for age, gender, coexisting conditions, serum albumin, income, and temporary vascular access a HR of 1.19 (95%CI:1.07-1.33) was observed in the group with eGFR≥15 mL/min/1.73 m(2). In the cohort of 3,897 "healthy" after adjusting for the same co-variates, HRs of 1.44 (95%CI: 1.08-1.65) and 1.65 (95%CI: 1.06-2.55) were obtained for the groups with baseline eGFR values of 10-14.9 and ≥15 mL/min/1.73 m(2), respectively. In "planned entry" patients (n=6,280), after adjusting for age, gender, co-morbidities, serum albumin and income, HRs in all groups were not significantly different as compared to the control group. HD initiation with eGFR>10 mL/min/1.73 m(2) shows no survival advantage. The higher mortality in the group with >eGFR starting dialysis looks like an "artifact" related to higher age, more co-morbidities, low albuminemia and the use of temporary vascular access.

Survival Trends in ESRD Patients Compared With the General Population in the United States

Health care resources expended on patients with end-stage renal disease (ESRD) have increased extensively, with uncertain changes in outcomes. In this study, we examined survival trends in the United States in patients with ESRD receiving renal replacement therapy with long-term dialysis or transplantation relative to the general population. Secondary analysis of records from the US Renal Data System. American adults receiving renal replacement therapy in 1977, 1987, 1997, and 2007. Year. 1-year survival. Abridged period life tables were created for each cross-sectional patient group and were compared with general US population life tables to measure relative survival, calculated as differences in average survival between the general US and the ESRD populations. From 1977 to 2007, ESRD patient groups became significantly older (mean age increased from 47 to 58 years) and sicker (ESRD due to diabetes increased from 9.1% to 38.2%; patients with a high death risk increased from 36.8% to 50.7%). Unadjusted age-specific survival improved (for 50-year-olds, average life expectancy increased 8% from 7.3 years in 1977 to 7.9 years in 2007), but age-specific survival increased more extensively in the general US population (from 27.5 years in 1977 to 30.9 years in 2007; 12% improvement). Accounting for this, age-specific relative survival in patients with ESRD decreased (for 50-year-olds, 20.2 life-years lost in 1977 vs 23.0 life-years lost in 2007). Our analysis controlled for neither patient comorbid conditions nor initial glomerular filtration rate at the start of renal replacement therapy. Over the past 4 decades, age-specific survival in patients with ESRD has improved, but has not kept pace with that of the general US population. To be complete, future survival studies in patients with ESRD should focus on both temporal changes in survival within this group and changes relative to the general population.