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1.  UMOD as a susceptibility gene for end-stage renal disease 
BMC Medical Genetics  2012;13:78.
In recent genetic association studies, common variants including rs12917707 in the UMOD locus have shown strong evidence of association with eGFR, prevalent and incident chronic kidney disease and uromodulin urinary concentration in general population cohorts. The association of rs12917707 with end-stage renal disease (ESRD) in a recent case-control study was only nominally significant.
To investigate whether rs12917707 associates with ESRD, graft failure (GF) and urinary uromodulin levels in an independent cohort, we genotyped 1142 ESRD patients receiving a renal transplantation and 1184 kidney donors as controls. After transplantation, 1066 renal transplant recipients were followed up for GF. Urinary uromodulin concentration was measured at median [IQR] 4.2 [2.2-6.1] yrs after kidney transplantation.
The rs12917707 minor allele showed association with lower risk of ESRD (OR 0.89 [0.76-1.03], p = 0.04) consistent in effect size and direction with the previous report (Böger et al, PLoS Genet 2011). Meta-analysis of these findings showed significant association of rs12917707 with ESRD (OR 0.91 [0.85-98], p = 0.008). In contrast, rs12917707 was not associated with incidence of GF. Urinary uromodulin concentration was lower in recipients-carriers of the donor rs12917707 minor allele as compared to non-carriers, again consistent with previous observations in general population cohorts.
Our study thus corroborates earlier evidence and independently confirms the association between UMOD and ESRD.
PMCID: PMC3495046  PMID: 22947327
UMOD; Uromodulin; Polymorphisms; SNP; End-stage renal disease; Kidney transplantation
2.  Time to Renal Disease and End-Stage Renal Disease in PROFILE: A Multiethnic Lupus Cohort 
PLoS Medicine  2006;3(10):e396.
Renal involvement is a serious manifestation of systemic lupus erythematosus (SLE); it may portend a poor prognosis as it may lead to end-stage renal disease (ESRD). The purpose of this study was to determine the factors predicting the development of renal involvement and its progression to ESRD in a multi-ethnic SLE cohort (PROFILE).
Methods and Findings
PROFILE includes SLE patients from five different United States institutions. We examined at baseline the socioeconomic–demographic, clinical, and genetic variables associated with the development of renal involvement and its progression to ESRD by univariable and multivariable Cox proportional hazards regression analyses. Analyses of onset of renal involvement included only patients with renal involvement after SLE diagnosis (n = 229). Analyses of ESRD included all patients, regardless of whether renal involvement occurred before, at, or after SLE diagnosis (34 of 438 patients). In addition, we performed a multivariable logistic regression analysis of the variables associated with the development of renal involvement at any time during the course of SLE.
In the time-dependent multivariable analysis, patients developing renal involvement were more likely to have more American College of Rheumatology criteria for SLE, and to be younger, hypertensive, and of African-American or Hispanic (from Texas) ethnicity. Alternative regression models were consistent with these results. In addition to greater accrued disease damage (renal damage excluded), younger age, and Hispanic ethnicity (from Texas), homozygosity for the valine allele of FcγRIIIa (FCGR3A*GG) was a significant predictor of ESRD. Results from the multivariable logistic regression model that included all cases of renal involvement were consistent with those from the Cox model.
Fcγ receptor genotype is a risk factor for progression of renal disease to ESRD. Since the frequency distribution of FCGR3A alleles does not vary significantly among the ethnic groups studied, the additional factors underlying the ethnic disparities in renal disease progression remain to be elucidated.
Fcγ receptor genotype is a risk factor for progression of renal disease to ESRD but does not explain the ethnic disparities in renal disease progression.
Editors' Summary
Systemic lupus erythematosis (SLE, commonly known as “lupus”) is an illness of many manifestations that appear to result from the immune system attacking components of the body's own cells. One of the unfortunate effects of SLE is kidney damage, which can, in a minority of patients, progress to kidney failure (formally called “end-stage renal disease,” or ESRD). Compared to White Americans, other ethnic groups tend to develop renal complications of lupus more often and with worse outcomes.
Why Was This Study Done?
It is unclear why some people with lupus develop kidney problems. The purpose of this US-based study was to confirm the factors that increase the risk of kidney damage and kidney failure, particularly in racial and ethnic minority patients, and to determine which of these factors accelerate the pace of kidney disease. Knowing these risk factors could allow the development and targeting of interventions, such as screening tests and preventive treatments, to prevent long-term loss of kidney function in patients with lupus.
What Did the Researchers Do and Find?
The researchers measured a number of factors in a multi-ethnic group of 1,008 patients with lupus, almost half of whom had some degree of kidney involvement. They found that those who developed kidney damage after being diagnosed with lupus tended to be younger, to have had lupus for a longer time, and to have experienced more effects of lupus in general than those who did not have kidney involvement. Those who developed kidney problems were also more likely to have been unemployed, to have had fewer years of formal education, and to have had high blood pressure before developing kidney involvement. African-American and Texan Hispanic individuals with lupus were more likely to develop kidney involvement, and tended to develop it more rapidly, than White Americans or Puerto Rican Hispanic ethnicity. Actual kidney failure (ESRD requiring dialysis or kidney transplantation) was more likely to occur among Texan Hispanics with kidney involvement than in the other ethnic groups. Diabetes and high blood pressure were not found to predict ESRD, but people with a particular variant of a protein that helps antibodies bind to cells (know as Fc-gamma receptor IIIa, or FcγRIIIa) were found to be more likely to develop ESRD, and to develop it more quickly.
What Do These Findings Mean?
These results suggest that the emergence and progression of kidney disease in patients with lupus depends on medical, genetic, and socioeconomic factors. Because no single test or intervention can be expected to address all of these factors, those treating patients with lupus must remain aware of the complexity of their patients lives at a variety of levels. In particular, ethnic disparities in the risk of serious kidney disease remain to be addressed.
Additional Information.
Please access these Web sites via the online version of this summary at
MedlinePlus page on lupus
Lupus Foundation of America
American College of Rheumatology pages on lupus
Wikipedia entry on lupus (note: Wikipedia is a free Internet encyclopedia that anyone can edit)
PMCID: PMC1626549  PMID: 17076550
3.  Syndrome of rapid onset end stage renal disease in incident Mayo Clinic chronic hemodialysis patient 
Indian Journal of Nephrology  2014;24(2):75-81.
Despite decades of research, a full understanding of chronic kidney disease (CKD)-end stage renal disease (ESRD) progression remains elusive. The common consensus is a predictable, linear, progressive and time-dependent decline of CKD to ESRD. Acute kidney injury (AKI) on CKD is usually assumed to be transient, with recovery as the expected outcome. AKI-ESRD association in current nephrology literature is blamed on the so-called “residual confounding.” We had previously described a relationship between AKI events and rapid onset yet irreversible ESRD happening in a continuum in a high-risk CKD cohort. However, the contribution of the syndrome of rapid onset-ESRD (SORO-ESRD) to incident United States ESRD population remained conjectural. In this retrospective analysis, we analyzed serum creatinine trajectories of the last 100 consecutive ESRD patients in 4 Mayo Clinic chronic hemodialysis units to determine the incidence of SORO-ESRD. Excluding 9 patients, 31 (34%) patients, including two renal transplant recipients, had SORO-ESRD: 18 males and 13 females age 72 (range 50-92) years. Precipitating AKI followed pneumonia (8), acutely decompensated heart failure (7), pyelonephritis (4), post-operative (5), sepsis (3), contrast-induced nephropathy (2), and others (2). Time to dialysis was shortest following surgical procedures. Concurrent renin angiotensin aldosterone system blockade was higher with SORO-ESRD - 23% versus 5%, P = 0.0113. In conclusion, SORO-ESRD is not uncommon among the incident general US ESRD population. The implications for ESRD care planning, AV-fistula-first programs, general CKD care and any associations with renal ageing/senescence warrant further study.
PMCID: PMC3968613  PMID: 24701038
Acute kidney injury; chronic kidney disease; end stage renal disease; renal replacement therapy
4.  Risk Factors for ESRD in HIV-Infected Individuals: Traditional and HIV-Related Factors 
Despite improvements in survival with HIV infection, kidney disease remains an important complication. Few studies have evaluated risk factors associated with development of end-stage renal disease (ESRD) in HIV-infected individuals. We sought to identify traditional and HIV-related risk factors for ESRD in HIV-infected individuals, and to compare ESRD risk by eGFR and proteinuria levels.
Study design
Retrospective cohort study.
Setting and Participants
22,156 HIV-infected veterans without preexisting ESRD receiving healthcare in the Veterans’ Affairs medical system between 1996 and 2004.
Hypertension, diabetes, cardiovascular disease, hypoalbuminemia (serum albumin<3.5mg/dL), CD4 lymphocyte count, HIV viral load, hepatitis C virus coinfection, proteinuria, and estimated glomerular filtration rate (eGFR) were identified using the Veterans’ Affairs electronic record system.
ESRD was ascertained by the United States Renal Data System.
366 cases of ESRD occurred, corresponding to 3 cases per 1,000 person-years. Hypertension (HR, 1.9; 95% CI, 1.5–2.4), diabetes (HR, 1.7; 95% CI, 1.3–2.2), and cardiovascular disease (HR, 2.2; 95% CI, 1.7–2.7) were independently associated with ESRD risk in multivariate-adjusted models, as were CD4 lymphocyte count <200 cells/mm3 (HR, 1.5; 95% CI, 1.2–2.0), HIV viral load ≥30,000 copies/mL (HR, 2.0; 95% CI, 1.5–2.8), hepatitis C virus coinfection (HR, 1.9; 95% CI, 1.5–2.4), and hypoalbuminemia (HR, 2.1; 95% CI, 1.8–2.5). Compared to persons without chronic kidney disease (CKD), defined as eGFR>60mg/min/1.73m2 and no proteinuria, lower eGFR and higher proteinuria categories were jointly associated with exponentially higher ESRD rates, ranging from 6.6 per 1000 person-years for persons with proteinuria 30–100 mg/dL and eGFR>60ml/min/1.73m2, to 193 per 1000 person-years for persons with proteinuria ≥300mg/dL and eGFR<30ml/min/1.73m2.
Results may not be generalizable to female and nonveteran populations.
In HIV-infected persons, ESRD risk appears attributable to a combination of traditional and HIV-related risk factors for kidney disease. Combining eGFR and proteinuria for CKD staging is most effective for stratifying risk for ESRD.
PMCID: PMC3324595  PMID: 22206742
End-stage renal disease; HIV; chronic kidney disease; risk factors
5.  Association of eGFR-Related Loci Identified by GWAS with Incident CKD and ESRD 
PLoS Genetics  2011;7(9):e1002292.
Family studies suggest a genetic component to the etiology of chronic kidney disease (CKD) and end stage renal disease (ESRD). Previously, we identified 16 loci for eGFR in genome-wide association studies, but the associations of these single nucleotide polymorphisms (SNPs) for incident CKD or ESRD are unknown. We thus investigated the association of these loci with incident CKD in 26,308 individuals of European ancestry free of CKD at baseline drawn from eight population-based cohorts followed for a median of 7.2 years (including 2,122 incident CKD cases defined as eGFR <60ml/min/1.73m2 at follow-up) and with ESRD in four case-control studies in subjects of European ancestry (3,775 cases, 4,577 controls). SNPs at 11 of the 16 loci (UMOD, PRKAG2, ANXA9, DAB2, SHROOM3, DACH1, STC1, SLC34A1, ALMS1/NAT8, UBE2Q2, and GCKR) were associated with incident CKD; p-values ranged from p = 4.1e-9 in UMOD to p = 0.03 in GCKR. After adjusting for baseline eGFR, six of these loci remained significantly associated with incident CKD (UMOD, PRKAG2, ANXA9, DAB2, DACH1, and STC1). SNPs in UMOD (OR = 0.92, p = 0.04) and GCKR (OR = 0.93, p = 0.03) were nominally associated with ESRD. In summary, the majority of eGFR-related loci are either associated or show a strong trend towards association with incident CKD, but have modest associations with ESRD in individuals of European descent. Additional work is required to characterize the association of genetic determinants of CKD and ESRD at different stages of disease progression.
Author Summary
Chronic kidney disease (CKD) affects about 6%–11% of the general population, and progression to end stage renal disease (ESRD) has a significant public health impact. Family studies suggest that the risk for CKD and ESRD is heritable. Unraveling the genetic underpinning of risk for these diseases may lead to the identification of novel mechanisms and thus diagnostic and therapeutic tools. We have previously identified 16 genetic markers in association with kidney function and prevalent CKD in general population studies. However, little is known about the relevance of these SNPs to the initial development of CKD or to ESRD risk. Therefore, we have now analyzed the association of these markers with the initiation of CKD in more than 26,000 individuals from the general population using serial estimations of kidney function, and with ESRD in four case-control studies in subjects of European ancestry (3,775 cases, 4,577 controls). We show that many of the 16 markers are also associated or show a strong trend towards association with initiation of CKD, while only 2 markers are nominally associated with ESRD. Further work is required to characterize the association of genetic determinants of different stages of CKD progression.
PMCID: PMC3183079  PMID: 21980298
6.  Association of Family History of ESRD, Prevalent Albuminuria, and Reduced GFR With Incident ESRD 
The contribution of albuminuria to the increased risk of incident end-stage renal disease (ESRD) in individuals with a family history of ESRD has not been well studied.
Study Design
Prospective cohort study.
Study Setting & Participants
We analyzed data for family history of ESRD collected from 19,409 participants of the Renal REGARDS (Reasons for Geographic and Racial Differences in Stroke) cohort study.
Family history of ESRD was ascertained by asking “Has anyone in your immediate family ever been told that he or she had kidney failure? This would be someone who is on or had been on dialysis or someone who had a kidney transplant.”
Study Outcomes
Incidence rate for ESRD.
Morning urine albumin-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR). Incident cases of ESRD were identified through the US Renal Data System.
A family history of ESRD was reported by 11.1% of participants. Mean eGFRs for those with and without a family history of ESRD were 87.5 ± 22.2 (SD) and 86.5 ± 19.3 mL/min/1.73 m2, respectively (P = 0.05) and the respective geometric mean ACRs were 12.2 and 9.7 mg/g (P < 0.001). ESRD incidence rates for those with and without a family history of ESRD were 244.3 and 106.1/100,000 person-years, respectively. After adjusting for age, sex, and race, the ESRD HR for those with versus those without a family history of ESRD was 2.13 (95% CI, 1.18-3.83). Adjustment for comorbid conditions and socioeconomic status attenuated this association (HR, 1.82; 95% CI, 1.00-3.28), and further adjustment for baseline eGFR and ACR completely attenuated the association between family history of ESRD and incident ESRD (HR, 1.12; 95% CI, 0.69-1.80).
The report of a family history of ESRD was not validated.
Family history of ESRD is common in older Americans and the increased risk of ESRD associated with a family history reflects lower GFR, higher albuminuria, and comorbid conditions.
PMCID: PMC3725825  PMID: 22078058
Race; albuminuria; end-stage renal disease; chronic kidney disease
7.  The FTO gene polymorphism is associated with end-stage renal disease: two large independent case–control studies in a general population 
Nephrology Dialysis Transplantation  2011;27(3):1030-1035.
Genome-wide association studies identified the FTO (fat mass and obesity gene) gene as an important determinant of body weight. More recently, the FTO gene was reported to be associated with other outcomes, including major risk factors for chronic kidney disease (CKD). We investigated the role of this gene in the risk of end-stage renal disease (ESRD) caused by CKD.
We conducted two large population-based case–control studies of ESRD. Study 1 compared 984 haemodialysed patients with ESRD with 2501 participants in the Czech post-MONICA study; Study 2 compared 1188 patients included in a kidney transplantation programme for ESRD with 6681 participants in the Czech HAPIEE study. The frequencies of the FTO rs17817449 single nucleotide polymorphism genotype were compared between cases and controls.
The FTO rs17817449 genotype was significantly associated with CKD in both studies (P-values 0.00004 and 0.006, respectively). In the pooled data, the odds ratios of CKD for GG and GT, versus TT genotype, were 1.37 (95% confidence interval 1.20–1.56) and 1.17 (1.05–1.31), respectively (P for trend <0.0001). Among haemodialysed and kidney transplant patients, the onset of ESRD in GG homozygotes was 3.3 (P = 0.012) and 2.5 (P = 0.032) years, respectively, earlier than in TT homozygotes.
These two large independent case–control studies in the general population found robust associations between the FTO rs17817449 polymorphism and the ESRD. The results suggest that the morbidities associated with the FTO gene include CKD.
PMCID: PMC3289895  PMID: 21788373
chronic kidney disease; end-stage renal disease; FTO; genetic epidemiology
8.  Marked Variation of the Association of ESRD Duration Before and After Wait Listing on Kidney Transplant Outcomes 
Numerous studies report a strong association between pretransplant end-stage renal disease (ESRD) duration and diminished transplant outcomes. However, cumulative waiting time may reflect distinct phases and processes related to patients’ physiological condition as well as pre-existing morbidity and access to care. The relative impact of pre- and postlisting ESRD durations on transplant outcomes is unknown. We examined the impact of these intervals from a national cohort of kidney transplant recipients from 1999 to 2008 (n = 112 249). Primary factors explaining prelisting ESRD duration were insurance and race, while primary factors explaining postlisting ESRD duration were blood type, PRA% and variation between centers. Extended time from ESRD to waitlisting had significant dose–response association with overall graft loss (AHR = 1.26 for deceased donors [DD], AHR = 1.32 for living donors [LD], p values < 0.001). Contrarily, time from waitlisting (after ESRD) to transplantation had negligible effects (p = 0.10[DD], p = 0.57[LD]). There were significant associations between pre- and postlisting ESRD time with posttransplant patient survival, however prelisting time had over sixfold greater effect. Prelisting ESRD time predominately explains the association of waiting time with transplant outcomes suggesting that factors associated with this interval should be prioritized for interventions and allocation policy. The degree to which the effect of prelisting ESRD time is a proxy for comorbid conditions, socioeconomic status or access to care requires further study.
PMCID: PMC3881969  PMID: 20645941
Access to care; African Americans; dialysis; ESRD; kidney transplantation; waiting list
9.  Incident Atrial Fibrillation and Risk of End-Stage Renal Disease in Adults with Chronic Kidney Disease 
Circulation  2012;127(5):569-574.
Atrial fibrillation (AF) frequently occurs in patients with chronic kidney disease (CKD). However, the long-term impact of development of AF on the risk of adverse renal outcomes in patients with CKD is unknown. In this study, we determined the association between incident AF and risk of end-stage renal disease (ESRD) among adults with CKD.
Methods and Results
We studied adults with CKD (defined as persistent glomerular filtration rate [eGFR] <60 ml/min/1.73 m2 by the CKD-EPI equation) enrolled in Kaiser Permanente Northern California who were identified between 2002–2010 and who did not have prior ESRD or previously documented AF. Incident AF was identified using primary hospital discharge diagnoses and/or two or more outpatient visits for AF. Incident ESRD was ascertained from a comprehensive health plan registry for dialysis and renal transplant. Among 206,229 adults with CKD, 16,463 developed incident AF. During a mean follow-up of 5.1± 2.5 years, there were 345 cases of ESRD that occurred after development of incident AF (74 per 1000 person-years) compared with 6505 cases of ESRD during periods without AF (64 per 1000 person-years, P<0.001). After adjustment for potential confounders, incident AF was associated with a 67% increase in rate of ESRD (hazard ratio 1.67, 95% confidence interval: 1.46–1.91).
Incident AF is independently associated with increased risk of developing ESRD in adults with CKD. Further study is needed to identify potentially modifiable pathways through which AF leads to a higher risk of progression to ESRD.
PMCID: PMC3676734  PMID: 23275377
arrhythmia; fibrillation; kidney
10.  The Renin-Aldosterone axis in kidney transplant recipients and its association with allograft function and structure 
Kidney international  2013;85(2):404-415.
The level of the renin-angiotensin-aldosterone system (RAAS) activity in kidney transplant recipients has not been extensively studied or serially profiled. To describe this axis and to determine its association with GFR change, interstitial expansion and end-stage renal disease (ESRD) we measured plasma renin activity (PRA) and plasma aldosterone levels annually for 5 years in 153 kidney transplant recipients randomly assigned to losartan or placebo. PRA and plasma aldosterone levels were in the normal range at all times and did not vary by immunosuppression regimen. Those on losartan exhibited higher PRA but similar plasma aldosterone levels. Neither baseline nor serial PRA or plasma aldosterone levels were associated with GFR decline, proteinuria or interstitial expansion. Losartan use, [HR 0.48 (95% CI 0.21–1.0), insignificant], and Caucasian donor, [HR 0.18 (95% CI 0.07–0.4), significant] were associated with less doubling of serum creatinine, death or ESRD. Hypertension, less than 3 HLA-matches, the combination of tacrolimus-rapamycin and acute rejection were associated with more events. Neither PRA nor plasma aldosterone levels were independently associated with this outcome. Higher serial plasma aldosterone levels were associated, however, with a significantly higher risk of ESRD, [HR 1.01 (95% CI 1.00–1.02)]. Thus, systemic RAAS is not overly activated in kidney transplant recipients but this may not reflect the intrarenal system. Importantly, plasma aldosterone levels may be associated with more ESRD.
PMCID: PMC3946607  PMID: 23965522
11.  Pediatric Renal Transplantation 
Although the number of children with end-stage renal disease (ESRD) in need for renal transplantation is small compared with adults, the problem associated with renal transplant in children are numerous, varied, and often peculiar. Pre-emptive transplantation has recently been growing in popularity as it avoids many of the associated long-term complications of ESRD and dialysis. Changes in immunosuppression to more potent agents over the years will have affected transplant outcome; there is also evidence that tacrolimus is more effective than cyclosporine. This review will discuss the short- and long-term complications such as acute and chronic rejection, hypertension, infections, and malignancies as well as factors related to long-term graft function.
Chronic allograft nephropathy is the leading cause of renal allograft loss in pediatric renal transplant recipients. It is likely that it reflects a combination of both immune and nonimmune injury occurring cumulatively over time so that the ultimate solution will rely on several approaches. Transplant and patient survival have shown a steady increase over the years. The major causes of death after transplantation are cardiovascular disease, infection and malignancy. Transplantation in special circumstances such as children with abnormal urinary tracts and children with diseases that have the potential to recur after transplantation will also be discussed in this review. Non-compliance with therapeutic regimen is a difficult problem to deal with and affects patients and families at all ages, but particularly so at adolescence. Growth may be severely impaired in children with ESRD which may result in major consequences on quality of life and self-esteem; a better height attainment at transplantation is recognized as one of the most important factors in final height achievement.
Although pediatric kidney transplantation is active in some parts of many developing countries, it is still inactive in many others and mostly relying on living donors. The lacking deceased programs in most of these countries is one of the main issues to be addressed to adequately respond to organ shortage.
In conclusion, transplantation is currently the best option for children with ESRD. Although improvement in immunosuppression demonstrated excellent results and has led to greater 1-year graft survival rates, chronic graft loss remains relatively unchanged and opportunistic infectious complications remain a problem
PMCID: PMC4089282  PMID: 25013625
Transplantation; Kidney; End-stage renal disease; Pediatrics
12.  Impact of MELD-Based Allocation on End-Stage Renal Disease after Liver Transplantation 
The proportion of patients undergoing liver transplantation (LT) with concomitant renal dysfunction markedly increased after allocation by the Model for End-stage Liver Disease (MELD) score was introduced. We examined the incidence of subsequent post-LT end-stage renal disease (ESRD) before and after the policy was implemented. Data on all adult deceased-donor LT recipients between 4/27/95 and 12/31/08 (n=59,242) from the Scientific Registry of Transplant Recipients were linked with Centers for Medicare & Medicaid Services ESRD data. Cox regression was used to (i) compare pre-MELD and MELD eras with respect to post-LT ESRD incidence (ii) determine the risk factors for post-LT ESRD (iii) quantify the association between ESRD incidence and mortality. Crude rates of post-LT ESRD were 12.8 and 14.5 per 1,000 patient-years in the pre-MELD and MELD eras, respectively. Covariate-adjusted post-LT ESRD risk was higher in the MELD era (hazard ratio [HR] =1.15; p=0.0049). African-American race, hepatitis C, pre-LT diabetes, higher creatinine, lower albumin, lower bilirubin and sodium>141 mMol/L at LT were also significant predictors of post-LT ESRD. Post-LT ESRD was associated with higher post-LT mortality (HR=3.32; p<0.0001). The risk of post-LT ESRD, a strong predictor of post-LT mortality, is 15% higher in the MELD era. This study identified potentially modifiable risk factors of post-LT ESRD. Early intervention and modification of these risk factors may reduce the burden of post-LT ESRD.
PMCID: PMC3203341  PMID: 21883908
End-stage renal disease; Liver transplant; Model for end-stage renal disease; Mortality; Scientific Registry of Transplant Recipients
13.  Sickle cell trait is not independently associated with susceptibility to end-stage renal disease in African Americans 
Kidney International  2011;80(12):1339-1343.
Conflicting reports exist as to whether sickle cell trait is a risk factor for the progression of nephropathy. In order to determine whether African Americans with sickle cell trait are at increased risk for kidney disease, we assessed the genetic association between sickle cell trait and end-stage renal disease (ESRD). Hemoglobin S, non-muscle myosin heavy chain 9 (MYH9), and apolipoprotein L1 (APOL1) risk variants were genotyped in 3258 unrelated African Americans: 1085 with non-diabetic ESRD, 996 with type 2 diabetes-associated ESRD, and 1177 controls. Since APOL1 is strongly associated with ESRD in African Americans, interactions between APOL1 and MYH9 risk variants and hemoglobin S were assessed using case-only and case-control centered two-way logistic regression interaction analyses. The sickle cell trait genotype frequencies were 8.7% in non-diabetic ESRD, 7.1% in type 2 diabetes-ESRD, and 7.2% in controls. There was no age-, gender-, and admixture-adjusted significance for sickle cell trait association with non-diabetic ESRD (odds ratio 1.16); type 2 diabetes-ESRD (odds ratio 1.01); or all-cause ESRD (combined non-diabetic and type 2 diabetic-ESRD patients compared to the controls; odds ratio 1.05) in dominant models. In addition, no evidence of APOL1 or MYH9 interactions with sickle cell trait was detected. Hence, sickle cell trait is not associated with diabetic or non-diabetic ESRD in a large sample of African Americans.
PMCID: PMC3280424  PMID: 21849968
African American; APOL1; diabetes; end-stage kidney disease; hemoglobin S; hypertension
14.  Estimating the long term impact of kidney donation on life expectancy and end stage renal disease 
Long term studies of live kidney donation do not show evidence of appreciable risks to the donor. However nephrectomy reduces total glomerular filtration rates (GFR) and is associated with increased rates of proteinuria and possibly hypertension. It is not clear to what extent these changes are associated with reduced life expectancy (LE) or increased risk of end stage renal disease (ESRD) since follow up is incomplete in most reports.
In a computer simulation model based on a US population chronic kidney disease model, increased hazard rates for higher blood pressure, proteinuria and low GFR were applied to healthy individuals undergoing donor nephrectomy. Subsequent LE and cumulative risk of ESRD were calculated.
Kidney donation is projected to reduce LE by 0.83 years and increase the absolute cumulative risk of ESRD by 0.89% for a 40-year-old white male. White females were predicted to have slightly greater loss of life and less added ESRD risk. Conversely, Blacks have greater risks of ESRD after donation. Older donors with hypertension were predicted to lose less life years and lower cumulative ESRD risks than young donors. Despite these increased risks most donors will have better life expectancy and lower ESRD rates than the general population since they are a highly selected cohort.
This study attempts to quantify increases in death and ESRD from donor nephrectomy assuming the risk factors of hypertension, low GFR and proteinuria have the same significance in this population as in the general population. Further study is required to better estimate the risks of donation and test whether these assumptions are valid.
PMCID: PMC3577426  PMID: 23414596
Quality of life; Nephrectomy; Live donation; End stage renal disease; Life expectancy
15.  Renal replacement therapy in Latin American end-stage renal disease 
Clinical Kidney Journal  2014;7(4):431-436.
The Latin American Dialysis and Renal Transplant Registry (RLADTR) was founded in 1991; it collects data from 20 countries which are members of Sociedad Latinoamericana de Nefrología e Hipertension. This paper presents the results corresponding to the year 2010. This study is an annual survey requesting data on incident and prevalent patients undergoing renal replacement treatment (RRT) in all modalities: hemodialysis (HD), peritoneal dialysis (PD) and living with a functioning graft (LFG), etc. Prevalence and incidence were compared with previous years. The type of renal replacement therapy was analyzed, with special emphasis on PD and transplant (Tx). These variables were correlated with the gross national income (GNI) and the life expectancy at birth. Twenty countries participed in the surveys, covering 99% of the Latin American. The prevalence of end stage renal disease (ESRD) under RRT in Latin America (LA) increased from 119 patients per million population (pmp) in 1991 to 660 pmp in 2010 (HD 413 pmp, PD 135 pmp and LFG 111 pmp). HD proportionally increased more than PD, and Tx HD continues to be the treatment of choice in the region (75%). The kidney Tx rate increased from 3.7 pmp in 1987 to 6.9 pmp in 1991 and to 19.1 in 2010. The total number of Tx's in 2010 was 10 397, with 58% deceased donors. The total RRT prevalence correlated positively with GNI (r2 0.86; P < 0.05) and life expectancy at birth (r2 0.58; P < 0.05). The HD prevalence and the kidney Tx rate correlated significantly with the same indexes, whereas the PD rate showed no correlation with these variables. A tendency to rate stabilization/little growth was reported in the most regional countries. As in previous reports, the global incidence rate correlated significantly only with GNI (r2 0.63; P < 0.05). Diabetes remained the leading cause of ESRD. The most frequent causes of death were cardiovascular (45%) and infections (22%). Neoplasms accounted for 10% of the causes of death. The prevalence of RRT continues to increase, particularly in countries with 100% public health or insurance coverage for RRT, where it approaches rates comparable to those displayed by developed countries with a better GNI. The incidence also continues to increase in both countries that have not yet extended its coverage to 100% of the population as well as in those that have an adequate program for timely detection and treatment of chronic kidney disease (CKD) and its associated risk factors. PD is still an underutilized strategy for RRT in the region. Even though renal Tx is feasible, its growth rate is still not as fast as it should be in order to compensate for the increased prevalence of patients on waiting lists. Diagnostic and prevention programs for hypertension and diabetes, appropriate policies promoting the expansion of PD and organ procurement as well as transplantation as cost-effective forms of RRT are needed in the region. Regional cooperation among Latin American countries, allowing the more developed to guide and train others in starting registries and CKD programs, may be one of the key initiatives to address this deficit.
PMCID: PMC4208784  PMID: 25349696
peritoneal dialysis; hemodialysis; kidney transplantation; chronic renal failure; Latin America
Clinical transplantation  2013;27(2):193-202.
The incidence of chronic kidney disease (CKD) in liver transplant recipients has been estimated to be from 18 to 28% at 10 years after transplantation. As outcomes from liver transplantation continue to improve, long-term native kidney function in these recipients becomes more critical to patient survival.
We analyzed 1151 adult, deceased-donor, single-organ primary liver transplantations performed at our center between 7/17/84 and 12/31/07. Analysis of renal function was performed on 972 patients with liver allograft survival >1 year.
Kaplan-Meier analysis revealed that 3%, 7%, and 18% of liver transplant recipients with allograft survival > 1 year developed ESRD at 5, 10, and 20 years, respectively. Significant independent risk factors for ESRD included dialysis during the transplant hospitalization, the stage of CKD at one year, hypercholesterolemia, non-Caucasian race, and hepatitis C as the primary indication for liver transplantation. The initial immunosuppression of essentially all recipients was a calcineurin-inhibitor based regimen.
Close, long-term follow-up of liver transplant recipients permits optimal management of liver allograft and native renal function, and can lead to excellent long-term outcomes despite a calcineurin inhibitor-based immunosuppressive regimen.
PMCID: PMC3622762  PMID: 23294013
End-stage renal disease; liver transplantation
17.  Kidney transplantation in HIV-positive patients: a report of 14 cases 
The HAART reduces the risk of HIV-related renal disease but the incidence of end-stage renal disease (ESRD). Therefore, efficacy and safety of renal transplantation (Tx) is an important resource in the HIV-infected population. We reported the results of kidney Tx in HIV+patients from deceased donors from June 2007 to March 2012 at our institution. The patients had to have CD4+T-cell counts≥200/mm3 and undetectable plasma HIV-RNA if on HAART. The induction immunosuppressive therapy consisted of metilprednisolone and basilixmab; tacrolimus and/or mycofenolic acid were used for maintenance therapy. The therapeutic drug monitoring (TDM) has been performed for the adjusting of both their doses [1]. A total of 14 patients underwent kidney Tx. They were on dialysis (haemodialysis=13, 92.9%; peritoneal=1, 7.1%) for 5±3.1 years and they were included on the Tx waiting list for 10±8 months. The baseline characteristics are showed in Table 1. Donor at baseline Mean age38±12.5 yearsDeceased14/14 (100%)High/unclassified infectious risk9 (64.29%)RecipientsMean age44 yearsPatients with previous AIDS-defining events3 (21.4%)Median follow-up months (IQR range)42.75 (8.5–55.2)Patient survival at last follow-up14/14 (100%)Graft survival at last follow-up13/14 (92.9%)Mean time of acute rejection since Tx28±20 daysPatients not treated with steroid at last follow-up6 (43%)Plasma creatinine at last follow-up1.87±1.93 mg/dlSevere infectious complications (CMV pneumonia, malaria, Kaposi sarcoma)3 (21.4%)Diabetes3 (21.4%)CMV infection without localization3 (21.4%)Bacterial pneumonia4 (28.6%)Reactivation of HIV RNA3 (21.4%)
At the last available point of follow-up (median=42.8 months, IQR=8.5–55.2), 8 out of the 13 patients (61.6%) without steroid had at least one acute rejection episode, but only 1 patient lost the graft, after 43 months (7.1%) due to chronic rejection associated with infectious and vascular complications. After Tx the median CD4+T-cell count increased from 382.5 (IQR range=233–415) to 434 (IQR range=282–605) cells/mm3 (p=0.055). In Figure 1 are reported the CD4+trends of 9 patients with a follow-up of at least 6 months.
HIV infection was well controlled, with only 2 (14.3%) cases of virological failure which were promptly resolved after HAART regimen modification. Table 1 shows the observed infectious complications. The skin Kaposi sarcoma has been resolved by switching to immunosuppressive therapy with sirolimus [2]. Kidney Tx appears to be safe in HIV-positive patients undergoing HAART. The viro-immunological parameters remained well controlled with no increases in infectious complications or neoplasm and a satisfactory control of HIV infection. However, the high rejection rate is a serious concern and suggests to consider a steroid-containing immunosuppressive regimen also in these patients.
PMCID: PMC3512470
18.  An epidemiologic model to project the impact of changes in glomerular filtration rate on quality of life and survival among persons with chronic kidney disease 
Predicting the timing and number of end-stage renal disease (ESRD) cases from a population of individuals with pre-ESRD chronic kidney disease (CKD) has not previously been reported. The objective is to predict the timing and number of cases of ESRD occurring over the lifetime of a cohort of hypothetical CKD patients in the US based on a range of baseline estimated glomerular filtration rate (eGFR) values and varying rates of eGFR decline.
A three-state Markov model – functioning kidney, ESRD, and death – with an annual cycle length is used to project changes in baseline eGFR on long-term health outcomes in a hypothetical cohort of CKD patients. Using published eGFR-specific risk equations and adjusting for predictive characteristics, the probability of ESRD (eGFR <10), time to death, and incremental cost-effectiveness ratios for hypothetical treatments (costing US$10, $5, and $2/day), are projected over the cohort’s lifetime under two scenarios: an acute drop in eGFR (mimicking acute kidney injury) and a reduced hazard ratio for ESRD (mimicking an effective intervention).
Among CKD patients aged 50 years, an acute eGFR decrement from 45 mL/minute to 35 mL/minute yields decreases of 1.6 life-years, 1.5 quality-adjusted life-years (QALYs), 0.8 years until ESRD, and an increase of 183 per 1,000 progressing to ESRD. Among CKD patients aged 60 years, lowering the hazard ratio of ESRD to 0.8 yields values of 0.2, 0.2, 0.2, and 46 per 1,000, respectively. Incremental cost-effectiveness ratios are higher (ie, less favorable) for higher baseline eGFR, indicating that interventions occurring later in the course of disease are more likely to be economically attractive.
Both acute kidney injury and slowing the rate of eGFR decline produce substantial shifts in expected numbers and timing of ESRD among CKD patients. This model is a useful tool for planning management of CKD patients.
PMCID: PMC4086666  PMID: 25061330
epidemiology; decision model; policy analysis; cost effectiveness; acute kidney injury; disease progression; end-stage renal disease
19.  End-stage renal disease risk in live kidney donors: what have we learned from two recent studies? 
Purpose of review
Living kidney donation improves the lives of those with kidney failure, but there are potential risks to the donor. We review two recent publications that describe the long-term risk of end-stage renal disease (ESRD) in living kidney donors.
Recent findings
One study reported that the long-term risk (median follow-up 15.1 years) of ESRD was, in relative terms, 11-fold higher in living kidney donors compared to healthy nondonors, and suggested a hereditary association since all affected donors were biologically related to their recipients and the causes were predominantly immunological diseases. In a second study, we estimated that the long-term risk (median follow-up 7.6 years) of ESRD was, in relative terms, eight-fold higher in living kidney donors compared to healthy matched nondonors. In both studies, the absolute increase in the 15-year incidence of ESRD from donation was below 0.5%. There are limitations in these studies, which have raised questions about the accuracy of the estimates of risk.
The results of these studies should be discussed with potential living kidney donors with an emphasis on the low 15-year incidence of ESRD following donation. The lifetime incidence of ESRD for donors of different age, race, and other characteristics requires further study.
PMCID: PMC4189686  PMID: 25160076
end-stage renal disease; living kidney donors; long-term outcomes
20.  Polymorphisms in MYH9 are associated with diabetic nephropathy in European Americans 
Nephrology Dialysis Transplantation  2011;27(4):1505-1511.
Polymorphisms in the non-muscle myosin IIA gene (MYH9) are associated with focal segmental glomerulosclerosis (FSGS) and non-diabetic end-stage renal disease (ESRD) in African Americans and FSGS in European Americans. We tested for association of single nucleotide polymorphisms (SNPs) in MYH9 with T2DM–ESRD in European Americans; additionally, three APOL1 gene variants were evaluated.
Fifteen MYH9 SNPs and two APOL1 SNPs plus a 6-bp deletion were genotyped in 1963 European Americans, 536 cases with T2DM–ESRD and 1427 non-nephropathy controls (467 with T2DM and 960 without diabetes).
Comparing T2DM–ESRD cases with the 467 T2DM non-nephropathy controls, single variant associations trending toward significance were detected with SNPs rs4821480, rs2032487 and rs4281481 comprising part of the major MYH9 E1 risk haplotype [P-values 0.053–0.055 recessive, odds ratio (OR) 6.08–6.14]. Comparing T2DM–ESRD cases to all 1427 non-nephropathy controls, we confirmed evidence of association in these three SNPs as well as in the fourth E1 SNP (rs3752462) (P-values 0.017–0.035, OR 1.41–3.72). APOL1 G1/G2 nephropathy risk variants were rare in individuals of European American heritage, present in 0.28% of chromosomes in T2DM–ESRD cases and 0.32% of controls.
MYH9 SNPs rs4821480, rs2032487, rs4281481 and rs3752462 are associated with T2DM–ESRD susceptibility in European Americans. The APOL1 risk variants are not present at appreciable frequency in this cohort with T2DM–ESRD. Therefore, polymorphisms in MYH9 appear to influence nephropathy risk in this sample.
PMCID: PMC3315672  PMID: 21968013
APOL1; diabetic nephropathy; end-stage renal disease; MYH9; type 2 diabetes mellitus
21.  Association of polymorphisms in the klotho gene with severity of non-diabetic ESRD in African Americans 
Nephrology Dialysis Transplantation  2010;25(10):3348-3355.
Background. Non-diabetic forms of nephropathy commonly lead to end-stage renal disease (non-DM ESRD). Previous studies have demonstrated that African Americans are more susceptible to non-DM ESRD compared to other ethnic groups, and this risk has a strong genetic component. A genome-wide scan for ESRD in African American families enriched for non-DM ESRD showed evidence for linkage in chromosome 13q33.3, and a candidate gene in this region, klotho, was selected for a detailed analysis in a follow-up case-control association study.
Methods. Thirty-four single-nucleotide polymorphisms (SNPs) in the klotho gene were genotyped in 317 unrelated African American non-DM ESRD cases and 354 non-nephropathy controls, including 12 SNPs identified by re-sequencing a region around exon 4.
Results. Two SNPs demonstrated modest admixture-adjusted evidence of association with non-DM ESRD, rs650439 (P = 0.013, recessive model) and rs643780 (P = 0.017, recessive model), while rs17643698 approached significance (P = 0.0953, two degrees of freedom test). Eight of the most significant SNPs were tested for replication in a second case-control collection (557 African American non-DM ESRD cases and 187 controls), and there was no evidence of association in replicate cases and controls; nor when the samples were combined for a total of 874 non-DM cases and 541 controls. Cox proportional hazards models were computed to test for association between polymorphisms in klotho and age at onset of ESRD. A three-SNP haplotype, rs526906, rs525014 and rs571118 (T/T/A), was associated with age of onset of ESRD [P = 0.007, recessive model; hazard ratio (HR) = 0.70]. Subjects homozygous for this haplotype had a mean 4 years later onset of ESRD, suggesting a slower disease progression. HapMap subjects homozygous for this haplotype had increased expression of klotho, further supporting a protective role of this variant in ESRD.
Conclusion. We conclude that three SNPs in intron 1 of the klotho gene are associated with delayed age at onset of non-DM ESRD in African Americans.
PMCID: PMC2948839  PMID: 20466664
genetics; klotho; non-diabetic ESRD
22.  New Susceptibility Loci Associated with Kidney Disease in Type 1 Diabetes 
Sandholm, Niina | Salem, Rany M. | McKnight, Amy Jayne | Brennan, Eoin P. | Forsblom, Carol | Isakova, Tamara | McKay, Gareth J. | Williams, Winfred W. | Sadlier, Denise M. | Mäkinen, Ville-Petteri | Swan, Elizabeth J. | Palmer, Cameron | Boright, Andrew P. | Ahlqvist, Emma | Deshmukh, Harshal A. | Keller, Benjamin J. | Huang, Huateng | Ahola, Aila J. | Fagerholm, Emma | Gordin, Daniel | Harjutsalo, Valma | He, Bing | Heikkilä, Outi | Hietala, Kustaa | Kytö, Janne | Lahermo, Päivi | Lehto, Markku | Lithovius, Raija | Österholm, Anne-May | Parkkonen, Maija | Pitkäniemi, Janne | Rosengård-Bärlund, Milla | Saraheimo, Markku | Sarti, Cinzia | Söderlund, Jenny | Soro-Paavonen, Aino | Syreeni, Anna | Thorn, Lena M. | Tikkanen, Heikki | Tolonen, Nina | Tryggvason, Karl | Tuomilehto, Jaakko | Wadén, Johan | Gill, Geoffrey V. | Prior, Sarah | Guiducci, Candace | Mirel, Daniel B. | Taylor, Andrew | Hosseini, S. Mohsen | Parving, Hans-Henrik | Rossing, Peter | Tarnow, Lise | Ladenvall, Claes | Alhenc-Gelas, François | Lefebvre, Pierre | Rigalleau, Vincent | Roussel, Ronan | Tregouet, David-Alexandre | Maestroni, Anna | Maestroni, Silvia | Falhammar, Henrik | Gu, Tianwei | Möllsten, Anna | Cimponeriu, Danut | Ioana, Mihai | Mota, Maria | Mota, Eugen | Serafinceanu, Cristian | Stavarachi, Monica | Hanson, Robert L. | Nelson, Robert G. | Kretzler, Matthias | Colhoun, Helen M. | Panduru, Nicolae Mircea | Gu, Harvest F. | Brismar, Kerstin | Zerbini, Gianpaolo | Hadjadj, Samy | Marre, Michel | Groop, Leif | Lajer, Maria | Bull, Shelley B. | Waggott, Daryl | Paterson, Andrew D. | Savage, David A. | Bain, Stephen C. | Martin, Finian | Hirschhorn, Joel N. | Godson, Catherine | Florez, Jose C. | Groop, Per-Henrik | Maxwell, Alexander P.
PLoS Genetics  2012;8(9):e1002921.
Diabetic kidney disease, or diabetic nephropathy (DN), is a major complication of diabetes and the leading cause of end-stage renal disease (ESRD) that requires dialysis treatment or kidney transplantation. In addition to the decrease in the quality of life, DN accounts for a large proportion of the excess mortality associated with type 1 diabetes (T1D). Whereas the degree of glycemia plays a pivotal role in DN, a subset of individuals with poorly controlled T1D do not develop DN. Furthermore, strong familial aggregation supports genetic susceptibility to DN. However, the genes and the molecular mechanisms behind the disease remain poorly understood, and current therapeutic strategies rarely result in reversal of DN. In the GEnetics of Nephropathy: an International Effort (GENIE) consortium, we have undertaken a meta-analysis of genome-wide association studies (GWAS) of T1D DN comprising ∼2.4 million single nucleotide polymorphisms (SNPs) imputed in 6,691 individuals. After additional genotyping of 41 top ranked SNPs representing 24 independent signals in 5,873 individuals, combined meta-analysis revealed association of two SNPs with ESRD: rs7583877 in the AFF3 gene (P = 1.2×10−8) and an intergenic SNP on chromosome 15q26 between the genes RGMA and MCTP2, rs12437854 (P = 2.0×10−9). Functional data suggest that AFF3 influences renal tubule fibrosis via the transforming growth factor-beta (TGF-β1) pathway. The strongest association with DN as a primary phenotype was seen for an intronic SNP in the ERBB4 gene (rs7588550, P = 2.1×10−7), a gene with type 2 diabetes DN differential expression and in the same intron as a variant with cis-eQTL expression of ERBB4. All these detected associations represent new signals in the pathogenesis of DN.
Author Summary
The global prevalence of diabetes has reached epidemic proportions, constituting a major health care problem worldwide. Diabetic kidney disease, or diabetic nephropathy (DN)—the major long term microvascular complication of diabetes—is associated with excess mortality among patients with type 1 diabetes. Even though DN has been shown to cluster in families, the underlying genetic and molecular pathways remain poorly defined. We have undertaken the largest genome-wide association study and meta-analysis to date on DN and on its most severe form of kidney disease, end-stage renal disease (ESRD). We identified new loci significantly associated with diabetic ESRD: AFF3 and an intergenic locus on chromosome 15q26 residing between RGMA and MCTP2. Our functional analyses suggest that AFF3 influences renal tubule fibrosis, a pathological hallmark of severe DN. Another locus in ERBB4 was suggestively associated with DN and resides in the same intronic region as a variant affecting the expression of ERBB4. Subsequent pathway analysis of the genes co-expressed with ERBB4 indicated involvement of fibrosis.
PMCID: PMC3447939  PMID: 23028342
23.  Evaluating the Contribution of the Cause of Kidney Disease to Prognosis in CKD: Results From the Study of Heart and Renal Protection (SHARP) 
The relevance of the cause of kidney disease to prognosis among patients with chronic kidney disease is uncertain.
Study Design
Observational study.
Settings & Participants
6,245 nondialysis participants in the Study of Heart and Renal Protection (SHARP).
Baseline cause of kidney disease was categorized into 4 groups: cystic kidney disease, diabetic nephropathy, glomerulonephritis, and other recorded diagnoses.
End-stage renal disease (ESRD; dialysis or transplantation) and death.
During an average 4.7 years' follow-up, 2,080 participants progressed to ESRD, including 454 with cystic kidney disease (23% per year), 378 with glomerulonephritis (10% per year), 309 with diabetic nephropathy (12% per year), and 939 with other recorded diagnoses (8% per year). By comparison with patients with cystic kidney disease, other disease groups had substantially lower adjusted risks of ESRD (relative risks of 0.28 [95% CI, 0.24-0.32], 0.40 [95% CI, 0.34-0.47], and 0.29 [95% CI, 0.25-0.32] for glomerulonephritis, diabetic nephropathy, and other recorded diagnoses, respectively). Albuminuria and baseline estimated glomerular filtration rate were associated more weakly with risk of ESRD in patients with cystic kidney disease than the 3 other diagnostic categories (P for interaction, <0.001 and 0.01, respectively). Death before ESRD was uncommon in patients with cystic kidney disease, but was a major competing risk for participants with diabetic nephropathy, whose adjusted risk of death was 2-fold higher than that of the cystic kidney disease group (relative risk, 2.35 [95% CI, 1.73-3.18]).
Exclusion of patients with prior myocardial infarction or coronary revascularization.
The cause of kidney disease has substantial prognostic implications. Other things being equal, patients with cystic kidney disease are at much higher risk of ESRD (and much lower risk of death before ESRD) than other patients. Patients with diabetic nephropathy are at particularly high risk of death prior to reaching ESRD.
PMCID: PMC4068325  PMID: 24613056
Kidney disease etiology; disease trajectory; end-stage renal disease (ESRD); disease progression; prognosis; cystic kidney disease; risk factor
24.  Predicting the risk of end-stage renal disease in the population-based setting: a retrospective case-control study 
BMC Nephrology  2011;12:17.
Previous studies of predictors of end-stage renal disease (ESRD) have limitations: (1) some focused on patients with clinically recognized chronic kidney disease (CKD); (2) others identified population-based patients who developed ESRD, but lacked earlier baseline clinical measures to predict ESRD. Our study was designed to address these limitations and to identify the strength and precision of characteristics that might predict ESRD pragmatically for decision-makers--as measured by the onset of renal replacement therapy (RRT).
We conducted a population-based, retrospective case-control study of patients who developed ESRD and started RRT. We conducted the study in a health maintenance organization, Kaiser Permanente Northwest (KPNW). The case-control study was nested within the adult population of KPNW members who were enrolled during 1999, the baseline period. Cases and their matched controls were identified from January 2000 through December 2004. We evaluated baseline clinical characteristics measured during routine care by calculating the adjusted odds ratios and their 95% confidence intervals after controlling for matching characteristics: age, sex, and year.
The rate of RRT in the cohort from which we sampled was 58 per 100,000 person-years (95% CI, 53 to 64). After excluding patients with missing data, we analyzed 350 cases and 2,114 controls. We identified the following characteristics that predicted ESRD with odds ratios ≥ 2.0: eGFR<60 mL/min/1.73 m2 (OR = 20.5; 95% CI, 11.2 to 37.3), positive test for proteinuria (OR = 5.0; 95% CI, 3.5 to 7.1), hypertension (OR = 4.5; 95% CI, 2.5 to 8.0), gout/positive test for uric acid (OR = 2.5; 95% CI, 1.8 to 3.5), peripheral vascular disease (OR = 2.2; 95% CI, 1.4 to 3.6), congestive heart failure (OR = 2.1; 95% CI, 1.4 to 3.3), and diabetes (OR = 2.1; 95% CI, 1.5 to 2.9).
The clinical characteristics needed to predict ESRD--for example, to develop a population-based, prognostic risk score--were often documented during routine care years before patients developed ESRD and required RRT.
PMCID: PMC3112083  PMID: 21545746
25.  Male Microchimerism at High Levels in Peripheral Blood Mononuclear Cells from Women with End Stage Renal Disease before Kidney Transplantation 
PLoS ONE  2012;7(3):e32248.
Patients with end stage renal diseases (ESRD) are generally tested for donor chimerism after kidney transplantation for tolerance mechanism purposes. But, to our knowledge, no data are available on natural and/or iatrogenic microchimerism (Mc), deriving from pregnancy and/or blood transfusion, acquired prior to transplantation. In this context, we tested the prevalence of male Mc using a real time PCR assay for DYS14, a Y-chromosome specific sequence, in peripheral blood mononuclear cells (PBMC) from 55 women with ESRD, prior to their first kidney transplantation, and compared them with results from 82 healthy women. Male Mc was also quantified in 5 native kidney biopsies obtained two to four years prior to blood testing and in PBMC from 8 women collected after female kidney transplantation, several years after the initial blood testing. Women with ESRD showed statistically higher frequencies (62%) and quantities (98 genome equivalent cells per million of host cells, gEq/M) of male Mc in their PBMC than healthy women (16% and 0.3 gEq/M, p<0.00001 and p = 0.0005 respectively). Male Mc was increased in women with ESRD whether they had or not a history of male pregnancy and/or of blood transfusion. Three out of five renal biopsies obtained a few years prior to the blood test also contained Mc, but no correlation could be established between earlier Mc in a kidney and later presence in PBMC. Finally, several years after female kidney transplantation, male Mc was totally cleared from PBMC in all women tested but one. This intriguing and striking initial result of natural and iatrogenic male Mc persistence in peripheral blood from women with ESRD raises several hypotheses for the possible role of these cells in renal diseases. Further studies are needed to elucidate mechanisms of recruitment and persistence of Mc in women with ESRD.
PMCID: PMC3293902  PMID: 22403639

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