Primary End-stage Renal Disease Research Articles

Methodological considerations in comparing access to Pre-emptive renal transplantation between SLE and other ESRD causes in the USRDS

We compared pre-emptive transplant rates between SLE and non-SLE end-stage renal disease (ESRD) from the U.S. Renal Data System (USRDS) and investigated the potential influence of frequency matching and primary ESRD causes in the non-SLE group. 4830 adult SLE patients with incident ESRD from USRDS 2005-2009 were frequency matched by age, sex and race to 4830 patients with incident non-SLE ESRD. Multivariable logistic regression models were used to estimate the odds of pre-emptive transplantation in SLE and non-SLE, and with the non-SLE subgroups by primary ESRD cause. The odds ratios (OR) of receiving a pre-emptive transplant were similar among non-SLE and SLE (referent group): OR = 1.18 (95% CI: 0.92, 1.50; p = 0.20). However, the ORs for receiving a pre-emptive transplant were 0.19 (95% CI: 0.08, 0.42) in type 2 diabetes ESRD, 0.42 (95% CI: 0.23, 0.75) for hypertension-associated ESRD, 1.67 (95% CI: 1.10, 2.54) in type 1 diabetes ESRD, and 2.06 (95% CI: 1.55, 2.73) for "other" ESRD. In contrast to non-SLE, younger SLE patients were less likely to receive a pre-emptive transplant than older SLE patients. The results of this study provide compelling evidence that major improvements need to be made in optimizing access to pre-emptive transplantation in SLE by addressing sociodemographic disparities and the unique challenges faced by SLE patients. Applying careful matching and selecting appropriate comparison groups in future studies may facilitate the development of effective strategies to address these barriers and to increase the number of pre-emptive renal transplants among SLE patients.

Validation of Systemic Lupus Erythematosus Diagnosis as the Primary Cause of Renal Failure in the US Renal Data System.

Using American College of Rheumatology (ACR) and Systemic Lupus International Collaborating Clinics (SLICC) criteria for systemic lupus erythematosus (SLE) classification as gold standards, we determined sensitivity, specificity, positive and negative predictive values (PPV and NPV) of having SLE denoted as the primary cause of end-stage renal disease (ESRD) in the US Renal Data System (USRDS). ESRD patients were identified by International Classification of Diseases, Ninth Revision codes in electronic medical records of 1 large tertiary care center, Montefiore Hospital, from 2006 to 2012. Clinical data were extracted and reviewed to establish SLE diagnosis. Data were linked by social security number, name, and date of birth to the USRDS, where primary causes of ESRD were ascertained. Of 7,396 ESRD patients at Montefiore, 97 met ACR/SLICC SLE criteria, and 86 had SLE by record only. Among the 97 SLE patients, the attributed causes of ESRD in the USRDS were 77 SLE and 12 with other causes (unspecified glomerulonephritis, hypertension, scleroderma), and 8 missing. Sensitivity, specificity, PPV, and NPV for SLE in the USRDS were 79%, 99.9%, 93%, and 99.7%, respectively. Of the 60 patients with biopsy-proven lupus nephritis, 44 (73%) had SLE as primary ESRD cause in the USRDS. Attribution of the primary ESRD causes among SLE patients with ACR/SLICC criteria differed by race, ethnicity, and transplant status. The diagnosis of SLE as the primary cause of ESRD in the USRDS has good sensitivity, and excellent specificity, PPV, and NPV. Nationwide access to medical records and biopsy reports may significantly improve sensitivity of SLE diagnosis.

Association of RAC1 Gene Polymorphisms with Primary End-Stage Renal Disease in Chinese Renal Recipients

Background/ObjectiveRAC1 gene could influence susceptibility to renal failure by altering the activity and expression of Rac1, which is a member of the Rho family of small GTP-binding proteins. In clinical practice, renal transplantation provides the optimal treatment for people with end-stage renal disease (ESRD). The objective of this present study was to determine whether the RAC1 gene polymorphisms were associated with primary ESRD susceptibility in Chinese renal recipients.MethodsSix single nucleotide polymorphisms (SNPs) of RAC1 gene, including rs836488 T>C, rs702482 A>T, rs10951982 G>A, rs702483 A>G, rs6954996 G>A, and rs9374 G>A, were genotyped in 300 renal transplant recipients (cases) and 998 healthy Chinese subjects (controls) by using TaqMan SNP genotyping assay. Allele, genotype, and haplotype frequencies of the six SNPs were compared between cases and controls. Odds ratios (OR) and 95% confidence intervals (CI) were calculated in logistic regression models to evaluate the associations of the six SNPs with ESRD risk.ResultsThe genotype distributions for the six SNPs in controls were consistent with Hardy-Weinberg equilibrium (P > 0.05). Association analysis revealed that three SNPs were significantly associated with ESRD risk. Positive associations with ESRD risk were found for the rs836488, rs702482, and rs702483 in the co-dominant model (minor allele homozygotes versus major allele homozygotes); specifically, the frequencies of the minor allele homozygotes and the minor allele for the three SNPs were higher in the cases than in the controls. In addition, these three SNPs also had associations with increased ESRD risk under the additive model (P < 0.05), and positive associations were also found for the rs836488 in the dominant model (P < 0.05) and for the rs702483 in the recessive model (P < 0.05). All these associations were independent of confounding factors. The other three SNPs (rs10951982, rs6954996, and rs9374), in all comparison models, were not associated with ESRD risk (P > 0.05). In haplotype analysis, carriers with "C-T-G-G-G-G" haplotype had a significantly higher risk of ESRD compared with the most common haplotype "T-A-G-A-G-G" (P = 0.011, OR = 1.46, 95% CI = 1.09–1.94).ConclusionThis study suggested that polymorphisms of RAC1 gene might influence the susceptibility to ESRD in Chinese Han population. Further studies are necessary to confirm our findings.

Cancer Incidence Among US Medicare ESRD Patients Receiving Hemodialysis, 1996-2009

Patients with end-stage renal disease (ESRD) receiving dialysis have been reported to have increased risk of cancer. However, contemporary cancer burden estimates in this population are sparse and do not account for the high competing risk of death characteristic of dialysis patients. Retrospective cohort study. US adult patients enrolled in Medicare's ESRD program who received in-center hemodialysis. Demographic/clinical characteristics. For overall and site-specific cancers identified using claims-based definitions, we calculated annual incidence rates (1996-2009). We estimated 5-year cumulative incidence since dialysis therapy initiation using competing-risk methods. We observed a constant rate of incident cancers for all sites combined, from 3,923 to 3,860 cases per 100,000 person-years (annual percentage change, 0.1; 95% CI,-0.4 to 0.6). Rates for some common site-specific cancers increased (ie, kidney/renal pelvis) and decreased (ie, colon/rectum, lung/bronchus, pancreas, and other sites). Of 482,510 incident hemodialysis patients, cancer was diagnosed in 37,128 within 5 years after dialysis therapy initiation. The 5-year cumulative incidence of any cancer was 9.48% (95% CI, 9.39%-9.57%) and was higher for certain subgroups: older age, males, nonwhites, non-Hispanics, nondiabetes primary ESRD cause, recent dialysis therapy initiation, and history of transplantation evaluation. Among blacks and whites, we observed 35,767 cases compared with 25,194 expected cases if the study population had experienced rates observed in the US general population (standardized incidence ratio [SIR], 1.42; 95% CI, 1.41-1.43). Risk was most elevated for cancers of the kidney/renal pelvis (SIR, 4.03; 95% CI, 3.88-4.19) and bladder (SIR, 1.57; 95% CI, 1.51-1.64). Claims-based cancer definitions have not been validated in the ESRD population. Information for cancer risk factors was not available in our data source. These results suggest a high burden of cancer in the dialysis population compared to the US general population, with varying patterns of cancer incidence in subgroups.

Should we treat asymptomatic bacteriuria after renal transplantation?

Infections remain a major cause of morbidity and mortality in the modern kidney transplantation era [1]. Symptomatic urinary tract infections (UTIs), which are defined as the association of a positive urine culture with the presence of symptoms or signs referable to UTI, are usually divided into lower tract (cystitis) and upper tract (pyelonephritis) infections. It is the most common infection in this population, both short-term as well as long-term post-transplantation [2]. As a consequence, UTI is the leading cause of antibiotic administration in kidney transplant recipients [3]. The highest incidence of symptomatic UTIs occurs during the first months after transplantation [4, 5]. In a registry study conducted by the Spanish Network for Research on Infection in Transplantation (RESITRA) in 2052 kidney transplant recipients with at least 1 year of follow-up, symptomatic UTIs occurred in 150 patients (7.3%) with an incidence rate of 0.45 episodes per 1000 transplantation days [4]. Escherichia coli and Enterococcus are known to account for more than half of bacterial UTIs post-kidney transplantation [2–5]. In a time of increasing resistance to antimicrobial agents and rising health-related costs, factors that trigger UTIs need to be understood, and if possible prevented. As in the general population, female gender is the strongest risk factor for UTI in kidney transplant recipients [4, 6, 7]. In comparison with men, the shorter urethra contributes to this phenomenon. Other risk factors such as advanced age, diabetes mellitus, primary end-stage renal disease, urinary tract abnormalities, cadaveric donor kidney, graft dysfunction and rejection, CMV infection and prolonged time on dialysis prior to transplantation have been pinpointed in some series [2, 6–10]. Identification of treatable risk factors is of interest as it may lead to a reduction in the frequency of symptomatic UTIs. Whether asymptomatic bacteriuria is a modifiable risk factor for symptomatic episodes and could impact the global prognosis of the transplanted patient (and should therefore be screened for and treated) remains controversial [11]. The Infectious Diseases Society of America (IDSA) defines asymptomatic bacteriuria as isolation of a specified quantitative count of bacteria (≥10 CFU/mL) in an appropriately collected urine sample obtained from a person without symptoms or signs referable to a UTI [12]. While a single urine specimen is sufficient to define asymptomatic bacteriuria in men, it is usually defined in women as two consecutively voided urine specimens with isolation of the same bacterial strain in quantitative counts ≥10 CFU/mL. This definition stems from a study showing that, in non-transplanted women, when the first specimen contains at least 10 bacteria per millilitre of urine, there is an 80% probability that the patient has true bacteriuria [13]. That 20% of women have a negative second culture is thought to reflect transient bacteriuria rather than contamination [14]. Asymptomatic bacteriuria is a common event after renal transplantation. For instance, Fiorante et al. showed that 51% of the recipients develop asymptomatic bacteriuria—as defined by the IDSA guidelines—during the 3 years following transplantation [15]. Therefore, the question of its management remains a daily unsolved problem for transplant physicians. Antibiotic overuse could lead to the emergence of bacterial resistance and antimicrobial agents’ side effects. In addition, important costs are associated with the strategy of systematic screening and treatment of post-kidney transplantation asymptomatic bacteriuria, such as the costs of urinalyses, antibiotics and even hospitalization of asymptomatic patients. This is a matter of concern in a time of limited health-care resources. To date, no study has demonstrated a clear benefit in treating asymptomatic bacteriuria with antimicrobial agents in kidney transplant recipients [15–17]. Of the studies published addressing this question, only one was prospective. This small trial, conducted in 88 Iranian patients, did not show a statistically significant decreased rate of symptomatic UTIs when kidney transplant recipients with asymptomatic bacteriuria were treated with a 10-day course of antibiotics [17]. Nine of the 43 treated patients (21%) developed symptomatic UTI during the 9–12 months of follow-up, in comparison with 14 F U L L R E V IE W

Diagnosis of cardiac disease in pediatric end-stage renal disease

Cardiac disease is a significant cause of morbidity and mortality in children with end-stage renal disease (ESRD). This study aimed to report the frequency of cardiac disease diagnostic methods used in US pediatric maintenance hemodialysis patients. A cross-sectional analysis of all US pediatric (ages 0.7-18 years, n = 656) maintenance hemodialysis patients was performed using data from the Centers for Medicare and Medicaid Services ESRD Clinical Performance Measures Project. Clinical and laboratory information was collected in 2001. Results were analysed by age, sex, race, Hispanic ethnicity, dialysis duration, body mass index (BMI), primary ESRD cause and laboratory data. Ninety-two percent of the patients had a cardiovascular risk factor (63% hypertension, 38% anemia, 11% BMI > 94th percentile, 63% serum phosphorus > 5.5 mg/dL and 55% calcium-phosphorus product ≥ 55 mg(2)/dL(2)). A diagnosis of cardiac disease was reported in 24% (n = 155) of all patients: left ventricular hypertrophy/enlargement 17%, congestive heart failure/pulmonary edema 8%, cardiomyopathy 2% and decreased left ventricular function 2%. Thirty-one percent of patients were not tested. Of those tested, the diagnostic methods used were chest X-rays in 60%, echocardiograms in 35% and electrocardiograms in 33%; left ventricular hypertrophy/enlargement was diagnosed using echocardiogram (72%), chest X-ray (20%) and electrocardiogram (15%). Although 92% of patients had cardiovascular risk factors, an echocardiography was performed in only one-third of the patients. Our study raises the question of why echocardiography, considered the gold standard for cardiac disease diagnosis, has been infrequently used in pediatric maintenance dialysis patients, a high-risk patient population.

Can Preemptive Kidney Transplantation Guarantee Longer Graft Survival in Living-Donor Kidney Transplantation? Single-Center Study

The benefit of preemptive kidney transplantation (KTx) for graft survival compared with nonpreemptive KTx is controversial. To analyze the influence of preemptive KTx on graft survival. The study included 476 of 531 patients who had undergone living-donor KTx between January 2000 and June 2007. Pediatric patients and those who had previously undergone KTx were excluded. Recipients were divided into 2 groups; group 1 included 413 patients (86.8%) who received grafts after institution of maintenance dialysis, and group 2 included 63 patients (13.2%) who underwent preemptive KTx. Donor type and HLA mismatch demonstrated significant differences between the 2 groups. Group 1 had more living donors and fewer HLA mismatches. Warm ischemia time in group 2 was significantly shorter than in group 1. The serum creatinine concentration in group 1 on postoperative day 7 was significantly higher than in group 2. Five- and 10-year graft survival in groups 1 and 2, respectively, were 95.3% and 81.3% vs 92.9% and 92.9%. Graft survival was not significant insofar as duration and method of dialysis. At our institution, independent risk factors for graft survival in living-donor KTx are primary end-stage renal disease, acute cellular rejection episodes, and recipient age. We observed no benefit on graft survival in recipients of living-donor KTx insofar as whether they had undergone previous dialysis.

Trends in Patient Characteristics and First-Year Medical Costs of Older Incident Hemodialysis Patients, 1995-2005

Characteristics of patients with chronic kidney disease who survive to end-stage renal disease may change over time, affecting subsequent outcomes and costs. We examined trends in older incident hemodialysis patient characteristics and analyzed first-year post-dialysis therapy initiation medical costs. Retrospective cohort study. All US incident hemodialysis patients aged > or =67 years at dialysis therapy initiation from January 1, 1995, to December 31, 2005, with Medicare Part A and Part B in the prior 2 years. Year of dialysis therapy initiation. Changes in patient characteristics and first-year costs. Mean and median values for continuous variables and percentages of categorical variables; first-year total medical costs measured per person per year. Observed costs were adjusted using Medicare Price Indices and patient case-mix. Median age at dialysis therapy initiation increased from 74.9 to 77.0 years from 1995 (n = 19,044) to 2005 (n = 31,796; P < 0.001). Diabetes prevalence increased from 54.2% to 64.1% (P < 0.001). Median estimated glomerular filtration rate increased from 8.0 to 11.2 mL/min/1.73 m(2), and median hemoglobin level increased from 9.4 to 10.2 g/dL. Obesity increased from 8.9% to 22.9% (P < 0.001). First-year observed costs increased by 37.9%; however, inflation-adjusted and case-mix-inflation-adjusted costs were stable. Important adjusters for costs are inability to ambulate/transfer, baseline serum albumin level, primary end-stage renal disease cause, comorbid peripheral vascular disease, and baseline hospital days. Population aged > or =67 years at dialysis therapy initiation and results may not generalize to the overall hemodialysis population. From 1995 to 2005, incident hemodialysis patients aged > or =67 years became older, sicker, and more obese with significantly increased estimated glomerular filtration rates and hemoglobin levels at dialysis therapy initiation. Increased first-year post-dialysis therapy initiation costs became stable over time after adjustment for price inflation; case-mix-inflation-adjusted costs remained constant, possibly because of mixed changes in patient characteristics.

Endoscopic Deflux ® injection for pediatric transplant reflux: A feasible alternative to open ureteral reimplant

Pediatric renal transplantation is frequently performed using a freely refluxing vesicoureteral anastomosis. The resulting vesicoureteral reflux (VUR) may increase the morbidity of urinary tract infections (UTIs) that commonly occur in this setting, yet open surgical correction of the refluxing anastomosis can prove difficult. We report our experience using endoscopic injection of dextranomer/hyaluronic acid (Deflux) to correct transplant VUR. We retrospectively reviewed the charts of patients treated with endoscopic injection of Deflux (Q-Med, Uppsala, Sweden) for VUR into their renal allograft. Indications for inclusion in the study were renal allograft transplantation for primary end-stage renal disease, radiographically proven VUR into the allograft, normal voiding history, and at least one documented febrile UTI. Preoperative and postoperative images, including voiding cystourethrogram and allograft ultrasound, were compared. Location of the transplant orifice and volume of Deflux were recorded. Clinical outcomes, including documented UTI and changes in serum creatinine following treatment, were also assessed. Eight patients were identified who were treated for transplant VUR, with a total of nine transplant ureters injected. Mean patient age at time of injection was 11.6 years (range: 7-19 years). Post-injection voiding cystourethrograms and allograft ultrasound were available for all patients. Following treatment, four ureters demonstrated resolution of VUR and one ureter demonstrated improvement to grade 1 VUR. The remaining four ureters demonstrated no change in VUR grade. No patients showed any change in their serum creatinine, and no episodes of transplant pyelonephritis have occurred during the follow-up period. Mean post-injection follow-up has been 17.3 months (range 9-26 months). Initial results demonstrate that endoscopic treatment with Deflux is feasible and may provide a less invasive alternative for treatment of transplant VUR. Further investigation with a larger group of patients and longer follow-up is needed.

Peritoneal dialysis in patients with congestive heart failure

Peritoneal dialysis (PD) may be a useful technique in the treatment of patients with congestive heart failure, both with and without primary end-stage renal disease (ESRD). In the treatment of patients with ESRD and congestive heart failure (CHF), PD has theoretical advantages compared with haemodialysis (HD), such as the absence of an arteriovenous fistula and the more gradual fluid removal. In cohort studies, the incidence of heart failure was less as compared with HD, however, randomized studies on this aspect are lacking. As an acute rescue treatment of patients with treatment refractory heart failure, functional improvement has been observed with the use of PD. However, fluid removal is less predictable compared with continuous haemofiltration therapies. As a long-term option for patients with treatment refractory CHF without ESRD, various case series showed improved functional performance and a reduction in hospitalization with the use of PD. However, also with the use of PD, median survival is still limited in these patients. Randomized studies are needed to establish the potential role of PD for this indication.

SPECIFIC OCULAR FINDINGS ATPATIENTS ON DIALYSIS

&amp;lt;p&amp;gt;Ocular changes at the patients on dialysis are numerous but unique,too. They are caused by primary end-stage renal disease, influence of dialysing itself and regular co-morbid condition. Purpose of this study is to indicate specific ocular finding among patients who are on dialysis. This prospective study assessed 81 patients on regular, chronic dialysis. They underwent complete ophthalmologic examination. The most common findings were the following: conjunctival calcification (53 eyes), cataract (43 eyes) and retinal microangio-pathies(atherosclerotic, hypertensive and occlusive-in total 168 eyes). All findings mentioned above were statistically significant (p&amp;amp;lt;0. 001) regarding to normal population. Ophthalmologist must be familiar with those abnormalities what is necessary for pointing out on special systemic co-morbid condition at the patients on dialysis.&amp;lt;/p&amp;gt;

Screening for Kidney Disease in Adults With Diabetes

Screening programs are generally aimed at conditions with a substantial public health impact and which benefit from early interventions. Chronic kidney disease (CKD), especially CKD attributed to diabetes, certainly fits this criterion. Diabetes remains the leading cause of end-stage renal disease (ESRD) in most countries in the world, accounting for 40–50% of incident ESRD cases (1–4). Due to the epidemic of diabetes secondary to obesity and the aging of the population, rates of kidney disease secondary to diabetes are on the rise. Within the past 2 decades, the incidence of ESRD secondary to diabetes in the U.S. has doubled while the prevalence of CKD among general Medicare patients diagnosed with both diabetes and hypertension has increased fourfold (1). Annual expenditures are highest for patients with ESRD secondary to diabetes compared with all other primary ESRD diagnoses (1). Thus, the epidemic of diabetes will certainly drive up health care costs for ESRD, which in the U.S. are projected to exceed $28 billion by 2010 (5). To prevent ESRD in individuals with diabetes, we must first do an adequate job of screening and detecting CKD. Unfortunately, the enormous burden of CKD remains undetected among adults with diabetes. The early detection of CKD among patients with diabetes has primarily involved the measurement of urinary albumin excretion. A timed urine collection confirmed on at least two of three occasions over a 6-month period was the initial method of screening. The acceptance of the use of the albumin (in milligrams)-to-creatinine (in grams) ratio measured in a random urine specimen has greatly expanded screening efforts due to the test’s convenience for both patients and physicians. Persistently increased levels of urine albumin excretion ≥30–299 mg/24 h or spot urine albumin-to-creatinine ratios ≥30–299 mg/g indicate the presence of microalbuminuria while urine albumin excretion levels higher than …

A comparison of peritonitis rates from the United States Renal Data System database: CAPD versus continuous cycling peritoneal dialysis patients

Previous comparisons of peritonitis rates between continuous ambulatory peritoneal dialysis (CAPD) and continuous cycling peritoneal dialysis (CCPD) have produced varying results. Using United States Renal Data System data, the authors evaluated peritonitis rates in 1994 through 1997 incident CAPD (n = 9,190) and CCPD (n = 2,785) Medicare patients. Patients were characterized during a 6-month entry period (months 4 through 9) and followed for a maximum of 2 years (months 10 through 33). Medicare claims data provided the date of the first peritonitis episode during the follow-up period. The time to first peritonitis after 9 months of PD was compared by the log-rank test, and then by Cox regression with adjustment for peritoneal dialysis modality, age, sex, race, primary end-stage renal disease (ESRD) diagnosis, number of entry-period hospital days, peritonitis during the entry period, hematocrit value, and congestive heart failure. For CAPD and CCPD, the adjusted average months to first peritonitis after 9 months of PD were 17.1 and 16.1, respectively. The probabilities of remaining without a peritonitis episode after 1 year of follow-up were 0.53 and 0.50, respectively ( P = 0.008). The risk of peritonitis was lower for CAPD than for CCPD (relative risk, 0.939; 95% confidence interval, 0.883 to 0.998). Other significant risk factors included age <or=44 years, black race, diabetes as primary ESRD diagnosis, peritonitis during the entry period, greater than 4 entry-period hospital days, and congestive heart failure. Patients treated with recombinant human erythropoietin with a hematocrit value of >or=36% had lower risk of peritonitis. Compared with CCPD, CAPD is associated with a slightly but significantly lower risk for development of a first peritonitis episode after 9 months of peritoneal dialysis therapy.

Endstage Renal Disease Owing to Diabetic Nephropathy in Mississippi

BackgroundDiabetic nephropathy (DN) is the leading cause of endstage renal disease (ESRD) in the United States. We reviewed our experience with DN as a cause of ESRD in a predominantly...