Mild Renal Disease Research Articles

Effect of renal impairment and haemodialysis on the pharmacokinetics of gemigliptin (LC15‐0444)

This study evaluated the effects of renal impairment (RI) and haemodialysis (HD) on the pharmacokinetics of gemigliptin, a novel dipeptidyl peptidase-4 (DPP-4) inhibitor. After a 100 mg administration to subjects with normal renal function (n = 23) or RI (n = 24), plasma, urine or dialysate samples were analysed. Control subjects were matched to patients based on age, gender and body mass index. Patients with mild, moderate, severe RI and end-stage renal disease (ESRD) showed 1.20, 2.04, 1.50 and 1.66-fold (1.10, 1.49, 1.22 and 1.21-fold) increase of mean area under the time-plasma concentration curve from 0 to infinity (AUCinf) [maximum plasma concentration (Cmax)] of gemigliptin, respectively. Pharmacokinetics of gemigliptin was comparable between HD and non-HD periods in ESRD patients. Less than 4% of the dose was removed by 4 h HD. RI appeared to have modest effect on the gemigliptin disposition. No dose adjustment in patients with RI is proposed on the basis of exposure-response relationship. Impact of HD on the removal of gemigliptin was negligible.

Does Mild Renal Failure Affect Coronary Flow Reserve after Coronary Artery Bypass Graft Surgery?

There are only a limited number of studies on the link between mild renal failure and coronary artery disease. The purpose of this study is to investigate the effects of mild renal failure on the distal vascular bed by measuring the coronary flow reserve (CFR) in transthoracic echocardiography after coronary artery bypass grafting (CABG). The study included 52 consecutive patients (12 women and 40 men) who had undergone uncomplicated CABG. The patients were divided into 2 groups. Group 1 included patients with a preoperative glomerular filtration rate (GFR) of 60-90 (mild renal failure), and group 2 included those with a GFR >90. The CFR measurements were carried out through a second harmonic transthoracic Doppler echocardiography. The mean age was 60.08 ± 1.56 years in group 1 and 60.33 ± 1.19 in group 2. The mean preoperative CFR was 1.79 ± 0.06 in group 1 and 2.05 ± 0.09 in group 2. The mean postoperative CFR was 2.09 ± 0.08 in group 1 and 2.37 ± 0.06 in group 2. There was a statistically significant difference between the 2 groups as to preoperative creatinine clearance, preoperative estimated GFR, postoperative day 7 creatinine clearance, postoperative month 6 creatinine clearance, postoperative day 7 estimated GFR, postoperative month 6 estimated GFR, preoperative CFR, and postoperative CFR (P < .05). CFR was found to be unaffected by the choice of on-pump or off-pump technique (P = .907). After bypass surgery, there was a significant increase in the mean postoperative CFR, when compared with the mean preoperative CFR (P = .001). In our study, we detected a decrease in CFR in patients with mild renal failure. We believe that in patients undergoing CABG for coronary artery disease, mild renal failure can produce adverse effects due to deterioration of the microvascular bed.

Warfarin treatment, kidney dysfunction and outcome in acute myocardial infarction patients with a history of atrial fibrillation

Recent studies suggest that warfarin increases the risk of ischemic stroke and mortality in people with end-stage renal disease and atrial fibrillation (AF). It is unknown at which degree of renal dysfunction the risk outweights the benefit. Cross-sectional study with prospective follow-up in the SWEDEHEART registry. Inclusion criteria were consecutive survivors of MI with history of AF and known serum creatinine (n=24317). Patients were classified into 5 renal disease stages according to their estimated glomerular filtration rate (eGFR). Primary outcome was a composite of death, readmission due to MI, ischemic stroke and bleeding within 1 year. Secondary outcomes were each event separately. Multivariate adjustment included age, sex, comorbidities, presentation, hospital course and discharge medication. A total of 5292 (21,7%) patients received warfarin at discharge. Warfarin treatment was significantly associated with lower risk for both the primary (HR and 95% CI 0.76 [0.72-0.81]) and secondary outcomes (Death, 0.67 [0.61, 0.73]; MI readmission 0.88 [0.81, 0.96]; Ischaemic stroke 0.58 [0.48, 0.71]) without increasing the risk of bleeding (1.04 [0.88, 1.23]). As many as 53,5% of patients had moderate to several renal disease (eGFR<60 ml/min/1.73 m2). For each renal disease strata, warfarin treatment was associated with a decreased risk of overall events as well as of death MI readmission or stroke alone. Bleeding events were neither increased nor reached statistical significance across differing degrees of renal dysfunction. View this table: Table 1. Fully adjusted Cox regression models showing hazards associated with warfarin use in individuals with differing renal function compared to equivalent individuals not receiving warfarin Warfarin treatment associated with a decreased 1-year risk of a composite event of death, readmission for MI, stroke and bleeding in MI patients with a history of AF. This was also true in individuals with mild, moderate and severe renal disease.

Postnatal outcome of congenital anomalies in low resource setting

This study aimed to determine the postnatal outcome of congenital malformations in a tertiary care hospital of India. This was a prospective study of all women with prenatally detected major congenital malformations. Postnatal follow-up of live born babies was carried out for 1 year. There were 574 cases with major congenital anomalies, 523 of which were fully followed. Only 69 women (13.6%) had the initial scan before 20 weeks of gestation. Craniospinal defects were the most common (42.7%), followed by genitourinary anomalies (28%). There was no live birth in cases such as anencephaly, iniencephaly, bilateral renal agenesis, gastroschisis, and cystic hygroma. Survival at 1 year was less than 25% in spina bifida, bilateral cystic kidneys, complex cardiac disease, and non-immune hydrops fetalis. In cases with mild hydrocephalus or unilateral and mild renal disease, the survival was over 75%. In India, the majority of congenital anomalies present late in gestation. Although fetal outcome is invariably poor for severe defects, existing legislation in the country leaves pregnancy continuation as the only option.

Pharmacokinetics of Teneligliptin in Subjects With Renal Impairment.

The pharmacokinetics of teneligliptin was compared in renally impaired and healthy subjects. Subjects were assigned to one of four groups of eight subjects, according to the stage of disease [mild, moderate, severe or end stage renal disease (ESRD)], while matched healthy subjects were allocated to one of two reference groups. Mild, moderate and severe renal impairment had no effect on maximum plasma concentration (Cmax ) following a single oral dose of 20 mg teneligliptin, as defined in the FDA guideline. AUC0-∞ was increased in all groups relative to the reference group but this was unrelated to the degree of renal impairment. Mean plasma protein binding was <80% in all groups. Overall, teneligliptin was well tolerated by subjects with renal impairment or ESRD. Dialysis is not expected to affect the efficacy or safety of teneligliptin. These results indicate that dose adjustment may not be needed when teneligliptin is administered to subjects with mild, moderate or severe renal impairment or ESRD.

Prevention of venous thromboembolism in hospitalized patients with chronic kidney disease

Despite the high morbidity and mortality associated with venous thromboembolism in hospitalized medical patients with a number of risk factors, and large evidence that prophylaxis is effective, prophylaxis rates remain elusive in medically ill patients. Furthermore, in patients with renal failure, prophylaxis often is omitted or sub-optimal, due to fear of provoking hemorrhage. Patients with end-stage renal disease often have platelet deficits. Low molecular weight heparin (LMWH) therapy may also be difficult to manage in these cases because LMWH clearance is largely dependent on the kidneys. Administration of LMWH to patients with some degree of renal failure may lead to bioaccumulation of anti-Xa activity with an increased risk of bleeding. In recent years, LMWH has largely replaced unfractionated heparin (UFH) for the treatment and prophylaxis of thromboembolic disease. LMWHs have been shown to be superior to UFH in the prevention of venous thromboembolism. They are also easier to administer and do not require laboratory monitoring. However, several case reports and a metaanalysis indicate that the use of LMWHs at therapeutic doses in patients with advanced renal failure can be associated with major bleeding with serious adverse effects. In this paper, we review recent evidence supporting the safety of LMWHs at prophylactic doses in patients with mild or moderate renal disease. Current evidence suggests that bioaccumulation of enoxaparin (the most widely used LMWH) can occur when the drug is used at standard therapeutic doses in patients with severely impaired renal function. This risk can be reduced by empiric dose reduction or monitoring of anti-Xa heparin levels.

Single-Center Evaluation of the Single-Dose Pharmacokinetics of the Angiotensin II Receptor Antagonist Azilsartan Medoxomil in Renal Impairment

Azilsartan medoxomil (AZL-M) is a potent angiotensin II receptor blocker that decreases blood pressure in a dose-dependent manner. It is a pro-drug and not detected in blood after oral administration because of rapid hydrolysis to the active moiety, azilsartan (AZL). AZL undergoes further metabolism to the major metabolite M-II and minor metabolites. The objective of this study was to determine the effect of renal impairment on the pharmacokinetics of AZL and its major metabolite. This was a single-center, open-label, phase I parallel-group study which examined the single-dose (40-mg) pharmacokinetics of AZL and M-II in 24 subjects with mild, moderate, or severe renal impairment or end-stage renal disease requiring hemodialysis (n=6 per group), respectively, and healthy matched subjects (n=24). Renal impairment/disease did not cause clinically meaningful increases in exposure to AZL. M-II exposure was higher in all renally impaired subjects and highest in those with severe impairment (approx fivefold higher vs. control). M-II is pharmacologically inactive; increased exposure was not considered important in dose selection for AZL-M in subjects with renal impairment. Hemodialysis did not significantly remove AZL or M-II. Renal impairment had no clinically meaningful effect on the plasma protein binding of AZL or M-II. Single doses of AZL-M 40mg were well tolerated in all subject groups. Based on the pharmacokinetic and tolerability findings, no dose adjustment of AZL-M is required for subjects with any degree of renal impairment, including end-stage renal disease.

405 HARPE STUDY: PREVALENCE OF RENAL ABNORMALITIES IN CHRONIC HBV INFECTION

Background and Aims: A close relationship exists between HBV infection and renal dysfunction. This study was undertaken to evaluate the degree of renal dysfunction in HBV positive patients in a university hospital in Mumbai and factors predicting it. Methods: We retrospectively analyzed 663 HBV positive patients presenting to our clinic from January 2010-June 2012 for renal dysfunction (estimated Glomerular Filtration rate (eGFR) by MDRD formula). Excluding 13 patients on maintenance hemodialysis and 66 with missing data, 584 patients (467 males; median age 43, range 9–80 years) were included. Results: Of 584 patients, 24 had acute hepatitis, 209 non-cirrhotic Chronic Hepatitis B (CHB), 214 were inactive carriers, 108 had CHB with cirrhosis, 22 were in immunotolerant phase, 6 had acuteon-chronic liver failure, 1 patient post liver transplant. Majority of patients were HBeAg negative (74.82%). 141 patients (24.1%) had comorbidities (diabetes mellitus and/or systemic hypertension). Serum creatinine was elevated (>1.5mg/ml) in 20 patients (2.7%) while eGFR (MDRD) was below normal ( 90ml/min/1.72m, 293 patients. Based on HBV disease status, renal function was different: In acute group (acute hepatitis, immunotolerant), 26.53% patients had mild renal dysfunction (eGFR 60–90ml/min/1.72m) versus chronic disease group (inactive carrier status, CHB, cirrhosis, others) with 44.49% (p =0.008). In multivariate analysis, age, gender, hypertension and chronic disease stage had significant association with reduced eGFR. 1 year follow-up eGFR values were available for 321 patients, of which 79 (25%) showed worsening of renal function by >20% while 58 patients (15%) showed >20% improvement. Within the cirrhotic population, Diabetes was significantly more prevalent than in other populations (33% of patients). 62/108 (57%) of cirrhotic patients had reduced renal function. Conclusion: HBV infection is associated with significant degree of reduced renal function, reaching up to 50% in the chronic population of our clinic. Comorbidities (25%) or antiviral treatment might further increase renal risk, therefore regular monitoring of renal function is recommended. MDRD formula was shown to be more sensitive than serum creatinine for renal function evaluation.

Accelerated Renal Fibrosis in Cardiorenal Syndrome Is Associated with Long-Term Increase in Urine Neutrophil Gelatinase-Associated Lipocalin Levels

Background: Cardiac events are the main cause of death among patients with end-stage renal failure. Even a mild renal disease is currently considered a major risk factor for cardiovascular complications following myocardial infarction (MI). The aim of the present study was to detect histological, sera and urine characteristics of kidney injury in cardiorenal syndrome (CRS) compared to chronic kidney disease (CKD) with an intact cardiac function. Methods: We employed a rat model for CRS, in which an acute MI (AMI) was induced 4 weeks after establishment of subtotal nephrectomy. Four weeks later, left ventricular function was assessed by echocardiography and changes in renal performance were examined using histological and biochemical parameters. Results: Increased interstitial fibrosis as well as renal inflammation were observed in renal sections derived from CRS rats, compared to subtotal nephrectomy (CKD)-only animals. Moreover, we found that even though AMI on the background of CKD was not associated with a further decrease in creatinine clearance or a further increase in sera BUN levels compared to CKD only, a significant long-term elevation in urine neutrophil gelatinase-associated lipocalin (Ngal) levels was detectable post-MI induction. Conclusions: AMI in the CKD setting is associated with accelerated renal fibrosis and long-term elevated urine Ngal values, suggesting that cardiac dysfunction contributes to accelerated intrinsic kidney injury in CKD. The data indicate that elevated urine Ngal may potentially serve as an early non-invasive laboratory parameter for a left ventricular dysfunction-related renal injury.

Impact of chronic kidney disease on outcomes after abdominal aortic aneurysm repair

Chronic kidney disease (CKD) is associated with increased morbidity and death after open abdominal aortic aneurysm (AAA) repair (OAR). This study highlights the effect of CKD on outcomes after endovascular AAA (EVAR) and OAR in contemporary practice. The National Surgical Quality Improvement Program (NSQIP) Participant Use File (2005-2008) was queried by Current Procedural Terminology (American Medical Association, Chicago, Ill) code to identify EVAR or OAR patients, who were grouped by CKD class as having mild (CKD class 1 or 2), moderate (CKD class 3), or severe (CKD class 4 or 5) renal disease. Propensity score analysis was performed to match OAR and EVAR patients with mild CKD with those with moderate or severe CKD. Comparative analysis of mortality and clinical outcomes was performed based on CKD strata. We identified 8701 patients who were treated with EVAR (n = 5811) or OAR (n = 2890) of intact AAAs. Mild, moderate, and severe CKD was present in 63%, 30%, and 7%, respectively. CKD increased (P < .01) overall mortality, with rates of 1.7% (mild), 5.3% (moderate), and 7.7% (severe) in unmatched patients undergoing EVAR or OAR. Operative mortality rates in patients with severe CKD were as high as 6.2% for EVAR and 10.3% for OAR. Severity of CKD was associated with increasing frequency of risk factors; therefore, propensity matching to control for comorbidities was performed, resulting in similar baseline clinical and demographic features of patients with mild compared with those with moderate or severe disease. In propensity-matched cohorts, moderate CKD increased the risk of 30-day mortality for EVAR (1.9% mild vs 3.2% moderate; P = .013) and OAR (3.1% mild vs 8.4% moderate; P < .0001). Moderate CKD was also associated with increased morbidity in patients treated with EVAR (8.3% mild vs 12.8% moderate; P < .0001) or OAR (25.2% mild vs 32.4% moderate; P = .001). Similarly, severe CKD increased the risk of 30-day mortality for EVAR (2.6% mild vs 5.7% severe; P = .0081) and OAR (4.1% mild vs 9.9% severe; P = .0057). Severe CKD was also associated with increased morbidity in patients treated with EVAR (10.6% mild vs 19.2% severe; P < .0001) or OAR (31.1% mild vs 39.6% severe; P = .04). The presence of moderate or severe CKD in patients considered for AAA repair is associated with significantly increased mortality and therefore should figure prominently in clinical decision making. The high mortality of AAA repair in patients with severe CKD is such that elective repair in such patients is not advised, except in extenuating clinical circumstances.

Investigating the role of MZB and B1 Cells in Sjögren’s Disease (159.22)

Abstract We have previously demonstrated that IL14a transgenic mice (IL14aTG) reproduce features of Sjogren’s disease (SD) seen in patients in the same relative time frame, including autoantibodies, early destruction of the salivary and lachrymal glands, infiltration of the salivary and lachrymal glands with lymphocytes, lymphocytic pneumonia, mild renal disease and eventually lymphoma (J.Immunol. 177: 5676, 2006 and Clin. Immunol. 130:304, 2009). We have more recently demonstrated that lymphotoxin is an important early mediator of salivary gland injury in IL14aTG mice and patients with SD (J.Immunol. 185: 6355, 2010). In our current studies we investigate the role of MZB and B1 cells in SD in IL14aTG mice. We demonstrate that IL14aTG mice lacking MZB cells (IL14aTG.CD19Cre.RBPj-/-) do not develop any features of SD up to the ages of 18 months. However, IL14aTG mice lacking Bruton’s tyrosine kinase (btk; IL14aTG.btk-/-), and hence B1 cells, develop more severe and accelerated SD with B cell lymphomas by 10 months of age, about 3 months earlier than IL-14a TG mice. Our hypothesis is that MZB and MZB precursors (MZBP) trafficking in the salivary and lachrymal glands are critical for inducing SD. Mice lacking B1 cells via the deletion of Bruton’s tyrosine kinase (btk) have accelerated SD because of increased numbers of MZB and MZBP along with decreased numbers of regulatory B cells. Current studies are evaluating these hypotheses.

Palliative resection of the primary tumour in stage IV rectal cancer

The aim of this study was to investigate the use of resection in a cohort of palliatively treated patients with stage IV rectal cancer. To avoid selection bias, particular attention was paid to correction for comorbidity and extent of disease. Patients with stage IV rectal cancer in two hospitals in Groningen were consecutively included over a 5-year period. Comorbidity was defined as major (dementia, cardiac failure or left ventricle ejection fraction <30%, or severe chronic obstructive pulmonary disease), minor (diabetes, hypertension, mild renal disease or mild pulmonary disease) or none. The effect of patient and disease characteristics on survival was assessed using Kaplan-Meier and Cox regression analyses. Of 88 patients, 11 (13%) underwent elective surgical resection without chemotherapy, 15 (17%) received both elective resection and chemotherapy, 21 (24%) underwent palliative chemotherapy only and 41 (47%) had supportive care only. The extent of disease (P<0.01), hospital (P=0.02) and comorbidity (P=0.04) were correlated with worse survival. Patients treated surgically survived for longer than patients treated nonsurgically, when the data were corrected for age, comorbidity, extent of disease and hospital [hazard ratio (HR)=0.4 (95% CI=0.2-0.7)]. Perioperative morbidity was seen in 38% of the patients, and 30-day mortality was 0%. In this retrospective cohort, resection was associated with longer survival independently of the extent of distant metastases, age and comorbidity.

A missense mutation in PKD1 attenuates the severity of renal disease

Mutations of PKD1 and PKD2 account for most cases of autosomal dominant polycystic kidney disease (ADPKD). Compared with PKD2, patients with PKD1 typically have more severe renal disease. Here, we report a follow-up study of a unique multigeneration family with bilineal ADPKD (NFL10) in which a PKD1 disease haplotype and a PKD2 (L736X) mutation co-segregated with 18 and 14 affected individuals, respectively. In our updated genotype-phenotype analysis of the family, we found that PKD1-affected individuals had uniformly mild renal disease similar to the PKD2-affected individuals. By sequencing all the exons and splice junctions of PKD1, we identified two missense mutations (Y528C and R1942H) from a PKD1-affected individual. Although both variants were predicted to be damaging to the mutant protein, only Y528C co-segregated with all of the PKD1-affected individuals in NFL10. Studies in MDCK cells stably expressing wild-type and mutant forms of PKD found that cell lines expressing the Y528C variant formed cysts in culture and displayed increased rates of growth and apoptosis. Thus, Y528C functions as a hypomorphic PKD1 allele. These findings have important implications for pathogenic mechanisms and molecular diagnostics of ADPKD.

Mild renal disease increases major bleeding in patients with atrial fibrillation undergoing percutaneous coronary stenting

Mild renal disease increases major bleeding in patients with atrial fibrillation undergoing percutaneous coronary stenting - …or why clinical cardiologists and interventionalists should be friends

The significance of mild renal dysfunction in chronic heart failure.

Heart failure is a major public health concern. Prediction models in heart failure have employed echo-cardiography and other advanced laboratory parameters in predicting the risk of mortality. However, most of the patients in the resource poor economies still do not have easy access to these advanced technology. To determine the clinical and echocardiographic correlates of patients with chronic heart failure (CHF) in the presence or mild renal disease (MRD). One hundred CHF patients were categorized based on their estimated glomerular filtration rates into either normal renal function or MRD. The clinical and echocardiographic variables of both groups were compared. There were 38 females and 62 males with an overall mean age of 54 years. A significantly greater proportion of patients with mild renal disease presented in New York Heart Association classes 3 and 4 (82.9% vs 27.1%). Patients with MRD had echocardiographic findings of a significantly larger left atrial dimension, lower ejection fraction and fractional shortening and shorter deceleration time. A significantly greater proportion of patients with mild renal disease also had moderate-severe mitral and tricuspid regurgitation and grades 2-3 diastolic dysfunction compared to patients without mild renal disease. Patients with MRD also exhibited a significantly greater degree of deterioration in the fractional shortening and ejection fraction compared to non-MRD patients. Multivariate regression analysis indicated that a low ejection fraction and a low fractional shortening were significantly associated with MRD. Identification of MRD in chronic heart failure patients using the estimated glomerular filtration rate is valuable in resource poor countries. The presence of MRD in CHF is associated with poor left ventricular function and increased deterioration of ventricular function.

Impact of Chronic Kidney Disease on Outcomes After Abdominal Aortic Aneurysm Repair

Chronic kidney disease (CKD) is associated with increased morbidity and death after open abdominal aortic aneurysm (AAA) repair (OAR). This study highlights the effect of CKD on outcomes after endovascular AAA repair (EVAR) and OAR in contemporary practice. The National Surgical Quality Improvement Program Participant Use File (2005-2008) was queried by Current Procedural Terminology code to identify EVAR or OAR patients who were grouped by CKD class as having mild (class 1, 2), moderate (class 3), or severe (class 4, 5) renal disease. Comparative analysis of mortality and clinical outcomes was performed based on CKD strata. CKD increased (P < .01) overall mortality with rates of 1.7% (mild), 5.3% (moderate), and 7.7% (severe) in unmatched patients. Rates in severe patients were as high as 6.2% for EVAR and 10.3% for OAR. Propensity matching to control for comorbidities was performed, resulting in similar baseline clinical and demographic features of patients with mild compared to those with moderate or severe disease. Even in matched cohorts, moderate and severe CKD increased the risk of 30-day mortality and complications compared with mild OAR and EVAR patients (Table I). On regression analysis, moderate and severe CKD independently predicted operative mortality and complications (Table II).Table IThirty-day outcomes in propensity-matched open repair (OAR) and endovascular aneurysm repair (EVAR) patients by degree of chronic kidney disease (CKD)CKD degree30-day mortality (%)Any complication (%)EVAROAREVAROARMild1.93.13.111Moderate3.2aP ≤ .01 compared with mild CKD.8.4aP ≤ .01 compared with mild CKD.8.4aP ≤ .01 compared with mild CKD.32aP ≤ .01 compared with mild CKD.Severe5.7aP ≤ .01 compared with mild CKD.9.9aP ≤ .01 compared with mild CKD.9.9aP ≤ .01 compared with mild CKD.25aP ≤ .01 compared with mild CKD.a P ≤ .01 compared with mild CKD. Open table in a new tab Table IIChronic kidney disease (CKD) independently predicts mortality and complication riskCKD degree30-day mortalityAny complicationOR (95% CI)OR (95% CI)EVAROAREVAROARModerate1.7 (1.1-2.7)aP ≤ .05 compared with mild.2.8 (1.8-4.5)aP ≤ .05 compared with mild.1.6 (1.3-2.0)aP ≤ .05 compared with mild.1.4 (1.2-1.8)aP ≤ .05 compared with mild.Severe1.5 (1.1-2.1)aP ≤ .05 compared with mild.1.6 (1.1-2.3)aP ≤ .05 compared with mild.1.4 (1.2-1.7)aP ≤ .05 compared with mild.1.2 (1.01-1.4)aP ≤ .05 compared with mild.CI, Confidence interval; EVAR, endovascular aneurysm repair; OAR, open aneurysm repair; OR odds ratio.a P ≤ .05 compared with mild. Open table in a new tab CI, Confidence interval; EVAR, endovascular aneurysm repair; OAR, open aneurysm repair; OR odds ratio. The presence of moderate or severe CKD in patients considered for AAA repair is associated with significantly increased mortality and therefore should figure prominently in clinical decision making.

Outcome and Predictors of Kidney Disease Progression in Puerto Ricans With Systemic Lupus Erythematosus Initially Presenting With Mild Renal Involvement

The aims of this study were to determine the outcomes and predictors of renal disease progression in Puerto Ricans with systemic lupus erythematosus (SLE) initially presenting mild renal involvement. A retrospective cohort of 61 patients with SLE (per American College of Rheumatology classification) with mild renal involvement was studied. Mild renal disease was defined as glomerular filtration rate (GFR) of 90 mL/min or higher in the presence of proteinuria (>0.25 g/d, but <3.5 g/d), hematuria, and/or urinary cellular casts. Demographic parameters, clinical manifestations, serologic markers, comorbidities, pharmacologic treatments, disease activity, and damage accrual were determined at onset of renal disease. Factors associated with renal disease progression were evaluated using recurrent event survival analysis. Of 61 patients, 55 (90.2%) were women. The mean (SD) age at renal onset was 29 (11.2) years, and the mean (SD) follow-up period was 5.1 (3.4) years. Thirty-eight patients had a decline in GFR. Thirty-two had a mild decline (GFR = 60-89 mL/min), 5 developed moderate to severe renal insufficiency (GFR = 15-59 mL/min), and 1 evolved to end-stage renal disease (GFR < 15 mL/min). In the Cox model, low C4 levels and proteinuria greater than 0.5 g/d were associated with an earlier decline in GFR. Most Puerto Rican patients with SLE initially presenting with mild renal involvement had a decrease in GFR after an average of 5 years of kidney disease, although most had a mild dysfunction. Low C4 levels and proteinuria were predictors of an earlier decline in GFR. We emphasize that awareness of these factors may contribute to early identification of individuals at risk for renal deterioration.

Investigating the role of interferon-alpha in Sjögren’s Disease (101.36)

Abstract We have previously demonstrated that IL14a transgenic mice (IL14aTG) reproduce features of Sjögren’s disease (SD) seen in patients in the same relative time frame, including autoantibodies, early destruction of the salivary and lachrymal glands, infiltration of the salivary and lachrymal glands with lymphocytes, lymphocytic pneumonia, mild renal disease and eventually lymphoma (J.Immunol. 177: 5676, 2006 and Clin. Immunol. 130:304, 2009). We have more recently demonstrated that lymphotoxin is an important early mediator of salivary gland injury in IL14aTG mice and patients with SD (J.Immunol. 185: 6355, 2010). In our current studies we investigate the role of interferon-alpha (IFN-α) in SD in IL14aTG mice. We demonstrate that IL14aTG mice lacking the type I IFN receptor (IL14aTG.IFNa/bR-/-) have the same early injury to the submandibular glands as IL14aTG mice. However, IL14aTG.IFNa/bR-/- do not get the later parotid gland injury that is seen in IL14aTG mice. Both IL14aTG mice and IL14aTG.IFNa/bR-/- get lung injury, but IL14aTG mice get a lymphocytic pneumonia and IL14aTG.IFNa/bR-/- get a mild perivascular and peribronchial lymphocytic infiltration. Thus, IFN-α is not critical in early stages of SD but involved in disease manifestations that occur after original salivary gland injury. These data have important implications for the use of IFN-α inhibitors in the treatment of SD.

Cystatin C and risk of vascular and nonvascular mortality: a prospective cohort study of older men

To assess the relevance of cystatin C, as a marker of mild-to-moderate renal impairment, for vascular and nonvascular mortality in older people. Prospective cohort study. Re-survey in 1997 to 1998 of survivors in the 1970 Whitehall study of London civil servants. Five thousand three hundred and seventy-one men (mean age at resurvey: 77 years) who took part in the resurvey and had plasma cystatin C concentration measured. Cause-specific mortality over subsequent 11 years (1997 to 2008). Cox regression was used to estimate the associations of cystatin C with vascular and nonvascular mortality, before and after adjustment for prior disease and other risk factors (including lifetime blood pressure). During an 11.0-year follow-up period, there were 1171 deaths from vascular causes [26 per 1000 per year (py)] and 1615 deaths from nonvascular causes (36 per 1000 py). Compared with men with cystatin C in the bottom fifth of the distribution, men in the top 10th had about two-fold higher mortality rates from vascular and nonvascular mortality (fully adjusted P both <0.001) even after adjustment for prior disease and all measured confounders, including lifetime blood pressure. The fully adjusted relative risks per 50% higher cystatin C concentrations were 1.66 [95% CI 1.48 to 1.85] for vascular mortality, 1.92 [95% CI 1.66 to 2.22] for ischaemic heart disease mortality and 1.46 [95% CI 1.31 to 1.61] for nonvascular mortality. In older men, plasma concentration of cystatin C, probably as a marker of mild renal disease, is a strong independent predictor of both vascular and nonvascular mortality.

La profilassi della tromboembolia venosa nei pazienti con malattia renale cronica

Summary Despite the high morbidity and mortality associated with venous thromboembolism in hospitalized medical patients with a number of risk factors, and large evidence that prophylaxis is effective, prophylaxis rates remain elusive in medically ill patients. Furthermore, in patients with renal failure, prophylaxis often is omitted or sub-optimal, due to fear of provoking hemorrhage. Patients with end-stage renal disease often have platelet deficits. Low molecular weight heparin (LMWH) therapy may also be difficult to manage in these cases because LMWH clearance is largely dependent on the kidneys. Administration of LMWH to patients with some degree of renal failure may lead to bioaccumulation of anti-Xa activity with an increased risk of bleeding. In recent years, LMWH has largely replaced unfractionated heparin (UFH) for the treatment and prophylaxis of thromboembolic disease. LMWHs have been shown to be superior to UFH in the prevention of venous thromboembolism. They are also easier to administer and do not require laboratory monitoring. However, several case reports and a meta-analysis indicate that the use of LMWHs at therapeutic doses in patients with advanced renal failure can be associated with major bleeding with serious adverse effects. In this paper, we review recent evidence supporting the safety of LMWHs at prophylactic doses in patients with mild or moderate renal disease. Current evidence suggests that bioaccumulation of enoxaparin (the most widely used LMWH) can occur when the drug is used at standard therapeutic doses in patients with severely impaired renal function. This risk can be reduced by empiric dose reduction or monitoring of anti-Xa heparin levels.