Related Articles

Background

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.

Methods

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.

Results

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.

Conclusions

Our study thus corroborates earlier evidence and independently confirms the association between UMOD and ESRD.

Objective. To review the contribution of vesicoureteral reflux and reflux nephropathy to end-stage renal disease. Data Source. Published research articles and publicly available registries. Results. Vesicoureteral reflux (VUR) is commonly identified in pediatric patients and can be associated with reflux nephropathy (RN), chronic kidney disease (CKD), and rarely end-stage renal disease (ESRD). Patients with reduced GFR, bilateral disease, grade V VUR, proteinuria, and hypertension are more likely to progress to CKD and ESRD. Because progression to ESRD is rare in VUR and often requires many decades to develop, there are limited prospective, randomized, controlled trials available to direct therapy to prevent progression to ESRD. Conclusions. Identification of patients with increased risk of progression to CKD and ESRD should be the goal of clinical, biochemical, and radiological evaluation of patients with VUR. Treatment of patients with VUR should be directed at preventing new renal injury and preserving renal function.

End-stage renal disease (ESRD) is defined as the inability of the kidneys to remove waste products and excess fluid from the blood. ESRD progresses from earlier stages of chronic kidney disease (CKD) and occurs when the glomerular filtration rate (GFR) is below 15 ml/minute/1.73 m2. CKD and ESRD are dramatically rising due to increasing aging population, population demographics, and the growing rate of diabetes and hypertension. Identification of multipotential stem/progenitor populations in mammalian tissues is important for therapeutic applications and for understanding developmental processes and tissue homeostasis. Progenitor populations are ideal targets for gene therapy, cell transplantation, and tissue engineering. The demand for kidney progenitors is increasing due to severe shortage of donor organs. Because dialysis and transplantation are currently the only successful therapies for ESRD, cell therapy offers an alternative approach for kidney diseases. However, this approach may be relevant only in earlier stages of CKD, when kidney function and histology are still preserved, allowing for the integration of cells and/or for their paracrine effects, but not when small and fibrotic end-stage kidneys develop. Although blood- and bone marrow-derived stem cells hold a therapeutic promise, they are devoid of nephrogenic potential, emphasizing the need to seek kidney stem cells beyond known extrarenal sources. Moreover, controversies regarding the existence of a true adult kidney stem cell highlight the importance of studying cell-based therapies using pluripotent cells, progenitor cells from fetal kidney, or dedifferentiated/reprogrammed adult kidney cells. Stem Cells 2010; 28:1649–1660.

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.

Chronic kidney disease (CKD) is a progressive loss in renal function over a period of months or years. End-stage renal disease (ESRD) or stage 5 CKD ensues when renal function deteriorates to under 15% of the normal range. ESRD requires either dialysis or, preferentially, a kidney organ allograft, which is severely limited due to organ shortage for transplantation. To combat this situation, one needs to either increase supply of organs or decrease their demand. Two strategies therefore exist: for those that have completely lost their kidney function (ESRD), we will need to supply new kidneys. Taking into account the kidneys' extremely complex structure, this may prove to be impossible in the near future. In contrast, for those patients that are in the slow progression route from CKD to ESRD but still have functional kidneys, we might be able to halt progression by introducing stem cell therapy to diseased kidneys to rejuvenate or regenerate individual cell types. Multiple cell compartments that fall into three categories are likely to be worthy targets for cell repair: vessels, stroma (interstitium) and nephron epithelia. Different stem/progenitor cells can be linked to regeneration of specific cell types; hematopoietic progenitors and hemangioblastic cell types have specific effects on the vascular niche (vasculogenesis and angiogenesis). Multipotent stromal cells (MSC), whether derived from the bone marrow or isolated from the kidney's non-tubular compartment, may, in turn, heal nephron epithelia via paracrine mechanisms. Nevertheless, as we now know that all of the above lack nephrogenic potential, we should continue our quest to derive genuine nephron (epithelial) progenitors from differentiated pluripotent stem cells, from fetal and adult kidneys and from directly reprogrammed somatic cells.

Background.

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.

Methods.

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.

Results.

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.

Conclusions.

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.

Introduction

End-stage renal disease (ESRD) is a major public health problem. Although kidney transplantation is a viable therapeutic option, this therapy is associated with significant limitations, including a shortage of donor organs. Induced pluripotent stem (iPS) cell technology, which allows derivation of patient-specific pluripotent stem cells, could provide a possible alternative modality for kidney replacement therapy for patients with ESRD.

Methods

The feasibility of iPS cell generation from patients with a history of ESRD was investigated using lentiviral vectors expressing pluripotency-associated factors.

Results

In the present article we report, for the first time, generation of iPS cells from kidney transplant recipients with a history of autosomal-dominant polycystic kidney disease (ADPKD), systemic lupus erythematosus, or Wilms tumor and ESRD. Lentiviral transduction of OCT4, SOX2, KLF4 and c-MYC, under feeder-free conditions, resulted in reprogramming of skin-derived keratinocytes. Keratinocyte-derived iPS cells exhibited properties of human embryonic stem cells, including morphology, growth properties, expression of pluripotency genes and surface markers, spontaneous differentiation and teratoma formation. All iPS cell clones from the ADPKD patient retained the conserved W3842X mutation in exon 41 of the PKD1 gene.

Conclusions

Our results demonstrate successful iPS cell generation from patients with a history of ESRD, PKD1 gene mutation, or chronic immunosuppression. iPS cells from autosomal kidney diseases, such as ADPKD, would provide unique opportunities to study patient-specific disease pathogenesis in vitro.

Background

Little is known about the racial differences in the incidence and progression of HIV-related chronic kidney disease (CKD) that underlie African American–white disparities in HIV-related end-stage renal disease (ESRD).

Methods

In a cohort in Baltimore, Maryland, we measured CKD incidence, glomerular filtration rate (GFR) slope, and progression to ESRD in 3332 African American and 927 white HIV-infected subjects.

Results

A total of 284 subjects developed CKD, 100 (35%) of whom subsequently developed ESRD. African American subjects were at slightly increased risk for incident CKD, compared with white subjects (hazard ratio [HR], 1.9 [95% confidence interval {CI}, 1.2–2.8]). However, once CKD had commenced, the African American subjects developed ESRD markedly faster than did the white subjects (HR, 17.7 [95% CI, 2.5–127.0]), and, correspondingly, their GFR decline after diagnosis of CKD was 6-fold more rapid (P < .001). In the subset of African American subjects for whom kidney-biopsy data were available, progression to ESRD was significantly faster than that in white subjects with CKD, irrespective of the presence of HIV-associated nephropathy.

Conclusions

The results of this study suggest that African American–white disparities in HIV-related ESRD are explained predominantly by a more aggressive natural disease history in African Americans and less by racial differences in CKD incidence.

Background

The prevalence of patients with end stage renal disease (ESRD) who need dialysis and/or transplantation has more than doubled in Thailand during the past two decades. It has been suggested that therapeutic strategies to reduce the risk of ESRD and other complications in CKD are now available, thus the early recognition and the institution of proven therapeutic strategies are important and beneficial. We, therefore, aimed to determine the prevalence of CKD in Thai adults from the National Health Examination Survey of 2004.

Methods

Data from a nationally representative sample of 3,117 individuals aged 15 years and older was collected using questionnaires, physical examination and blood samples. Serum creatinine was measured by Jaffé method. GFR was estimated using the Chinese modified Modification of Diet in Renal Disease Study equation. Chronic kidney Disease (CKD) stages were classified based on Kidney Disease Outcome Quality Initiative (K/DOQI).

Results

The prevalence of CKD in Thai adults weighted to the 2004 Thai population by stage was 8.1% for stage 3, 0.2% and 0.15% for stage 4 and 5 respectively. Compared to non-CKD, individuals with CKD were older, had a higher level of cholesterol, and higher blood pressure. Those with cardiovascular risk factors were more likely to have CKD (stage 3-5) than those without, including hypertension (OR 1.6, 95%CI 1.1, 3.4), diabetes (OR 1.87, 95%CI 1.0, 3.4). CKD was more common in northeast (OR 2.1, 95%CI 1.3, 3.3) compared to central region. Urinalysis was not performed, therefore, we could not have data on CKD stage 1 and 2. We have no specific GFR formula for Thai population.

Conclusion

The identification of CKD patients should be evaluated and monitored for appropriate intervention for progression to kidney disease from this screening.

Background

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.

Methods

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.

Results

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.

Conclusions

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.

ABSTRACT

BACKGROUND

Among older adults with chronic kidney disease (CKD), the comparative event rates of end-stage renal disease (ESRD) and cause-specific death are unknown.

OBJECTIVE

To compare the rates of ESRD, cardiovascular and non-cardiovascular death and examine risk factors for ESRD and all-cause mortality in Cardiovascular Health Study (CHS) participants.

Design

The CHS is a longitudinal cohort study of community-dwelling adults aged 65 years and older.

PARTICIPANTS

1,268 participants with an estimated glomerular filtration rate (eGFR) < 60 ml/min per 1.73 m2 were followed until the time of first event (ESRD, cardiovascular or non-cardiovascular death) or until March 31, 2003.

MAIN MEASURES

The outcomes were ESRD, cardiovascular- and non-cardiovascular death. Rates of each event were calculated, and a Cox Proportional Hazards Model with a competing risk framework was used to examine risk factors for ESRD as compared with death. Predictors included age, gender, race, BMI, hypertension, diabetes, cardiovascular disease, heart failure, tobacco use, eGFR, and total cholesterol.

KEY RESULTS

During 9.7 years of follow-up, 5% of the cohort progressed to ESRD, and 61% of the cohort died. The rate (per 100 person-years) was 0.5 for ESRD and 6.8 for all-cause mortality (3.0 for cardiovascular and 3.8 for non-cardiovascular mortality). In the competing risk framework, lower eGFR, male gender, African-American race, and higher BMI were associated with an increased risk of ESRD.

CONCLUSIONS

Older adults with CKD are 13-fold more likely to die from any cause than progress to ESRD and are 6-fold more likely to die from cardiovascular causes than develop ESRD.

Background

Validated prediction scores are required to assess the risks of end-stage renal disease (ESRD) and death in individuals with chronic kidney disease (CKD).

Study Design

Prospective cohort study with validation in a separate cohort.

Setting & Participants

Cox regression was used to assess the relevance of baseline characteristics to risk of ESRD (mean follow-up, 4.1 years) and death (mean follow-up, 6.0 years) in 382 patients with stages 3-5 CKD not initially on dialysis therapy in the Chronic Renal Impairment in Birmingham (CRIB) Study. Resultant risk prediction equations were tested in a separate cohort of 213 patients with CKD (the East Kent cohort).

Factors

44 baseline characteristics (including 30 blood and urine assays).

Outcomes

ESRD and all-cause mortality.

Results

In the CRIB cohort, 190 patients reached ESRD (12.1%/y) and 150 died (6.5%/y). Each 30% lower baseline estimated glomerular filtration rate was associated with a 3-fold higher ESRD rate and a 1.3-fold higher death rate. After adjustment for each other, only baseline creatinine level, serum phosphate level, urinary albumin-creatinine ratio, and female sex remained strongly (P < 0.01) predictive of ESRD. For death, age, N-terminal pro-brain natriuretic peptide, troponin T level, and cigarette smoking remained strongly predictive of risk. Using these factors to predict outcomes in the East Kent cohort yielded an area under the receiver operating characteristic curve (ie, C statistic) of 0.91 (95% CI, 0.87-0.96) for ESRD and 0.82 (95% CI, 0.75-0.89) for death.

Limitations

Other important factors may have been missed because of limited study power.

Conclusions

Simple laboratory measures of kidney and cardiac function plus age, sex, and smoking history can be used to help identify patients with CKD at highest risk of ESRD and death. Larger cohort studies are required to further validate these results.

Background

The aim of the study was to validate the Norwegian version of a self-administered 43-item questionnaire designed to assess quality of life in kidney transplant recipients, the End-Stage Renal Disease Symptom Checklist – Transplantation Module (ESRD-SCL).

Methods

In total, 53 kidney transplant recipients from one university-affiliated hospital responded to a questionnaire including the ESRD-SCL and the Short Form 36 (SF-36). We assessed internal consistency reliability and test-retest reliability with 2 weeks between assessments. Construct validity was assessed by correlations of the ESRD-SCL subscales with related and unrelated SF-36 scales, demographic, and clinical characteristics.

Results

Subscales of the ESRD-SCL showed good internal consistency reliability (Cronbach's = 0.72–0.81) and for the aggregate total scale α was 0.94. Test-retest reliability median 14 days apart was excellent with intraclass coefficients ranging from 0.87 to 0.95. The pattern of correlations of the ESRD-SCL scales with related and unrelated scales SF-36 scales and demographic and clinical characteristics gave support to the construct validity of the ESRD-SCL.

Conclusion

The Norwegian translation of the ESRD-SCL showed satisfactory internal consistency reliability, test-retest reliability and construct validity, at the level of the original German version.

The number of patients requiring renal replacement therapy due to end-stage renal disease (ESRD) is increasing worldwide. The prevalence of chronic kidney disease (CKD), and the importance of CKD as a risk factor in development of ESRD and in complicating cardiovascular disease (CVD) have been confirmed. In recent years, the involvement of angiogenesis-related factors in the progression of CKD has been studied, and the potential therapeutic effects on CKD of modulating these factors have been identified. Vascular endothelial growth factor (VEGF)-A, a potent pro-angiogenic factor, is involved in the development of the kidney, in maintenance of the glomerular capillary structure and filtration barrier, and in the renal repair process after injury. VEGF-A is also involved in the development of early diabetic nephropathy, demonstrated by the therapeutic effects of anti-VEGF-A antibody. Angiopoietin (Ang)-1 induces the maturation of newly formed blood vessels, and the therapeutic effects of Ang-1 in diabetic nephropathy have been described. In experimental models of diabetic nephropathy, the therapeutic effects of angiogenesis inhibitors, including angiostatin, endostatin and tumstatin peptides, the isocoumarin NM-3, and vasohibin-1, have been reported.

Further analysis of the involvement of angiogenesis-related factors in the development of CKD is required. Determining the disease stage at which therapy is most effective and developing an effective drug delivery system targeting the kidney will be essential for pro-or anti-angiogenic strategies for patients with CKD.

Background

Chronic kidney disease (CKD) leads to End Stage Renal Disease (ESRD) and is a growing epidemic throughout the world. In the United States, African Americans have an incidence of ESRD four times that of Whites.

Study Design

Cross Sectional to examine the prevalence and awareness of CKD in African Americans

Setting & Participants

Observational Cohort in the Jackson Heart Study (JHS)

Predictor

CKD was defined as estimated glomerular filtration rate < 60 ml/min/1.73 m2, presence of albuminuria, or being on dialysis

Outcomes and Measurements

Data from the Jackson Heart Study (JHS) were analyzed. Medical history including disease awareness and drug therapy, anthropometric measurements, serum, and urine samples were obtained from JHS participants at the baseline visit. Associations between CKD prevalence and awareness and selected demographic, socioeconomic, healthcare access, and disease status parameters were assessed utilizing logistic regression models.

Results

The prevalence of CKD in the JHS was 20%; CKD awareness was only 15.8%. Older participants had higher prevalence but were also more aware of CKD. Hypertension, diabetes, cardiovascular disease (CVD), hypercholesterolemia, hypertriglyceridemia, increasing age and waist circumference as well as being single or less physically active were associated with CKD. Only advancing of CKD stage was associated with awareness.

Limitations

Cross-sectional assessment, single urine measurement

Conclusions

The JHS has a high prevalence and low awareness of CKD, especially those with less severe disease status. This emphasizes the need for earlier diagnosis and increased education of health care providers and the general population.

Objective

To establish whether lithium or anticonvulsant should be used for maintenance treatment for bipolar affective disorder (BPAD) if the risks of suicide and relapse were traded off against the risk of end-stage renal disease (ESRD).

Method

Decision analysis based on a systematic literature review with two main decisions: (1) use of lithium or at treatment initiation and (2) the potential discontinuation of lithium in patients with chronic kidney disease (CKD) after 20 years of lithium treatment. The final endpoint was 30 years of treatment with five outcomes to consider: death from suicide, alive with stable or unstable BPAD, alive with or without ESRD.

Results

At the start of treatment, the model identified lithium as the treatment of choice. The risks of developing CKD or ESRD were not relevant at the starting point. Twenty years into treatment, lithium still remained treatment of choice. If CKD had occurred at this point, stopping lithium would only be an option if the likelihood of progression to ESRD exceeded 41.3% or if anticonvulsants always outperformed lithium regarding relapse prevention.

Conclusion

At the current state of knowledge, lithium initiation and continuation even in the presence of long-term adverse renal effects should be recommended in most cases.

Background

Chronic kidney disease (CKD) is a growing public health problem and end stage renal disease (ESRD) represents a large human and economic burden. It is important to identify patients at high risk of ESRD. In order to determine whether renal Doppler resistive index (RI) may discriminate those patients, we analyzed whether RI was associated with identified prognosis factors of CKD, in particular histological findings, and with renal outcome.

Methods

RI was measured in the 48 hours before renal biopsy in 58 CKD patients. Clinical and biological data were collected prospectively at inclusion. Arteriosclerosis, interstitial fibrosis and glomerulosclerosis were quantitatively assessed on renal biopsy in a blinded fashion. MDRD eGFR at 18 months was collected for 35 (60%) patients. Renal function decline was defined as a decrease in eGFR from baseline of at least 5 mL/min/ 1.73 m2/year or need for chronic renal replacement therapy. Pearson’s correlation, Mann–Whitney and Chi-square tests were used for analysis of quantitative and qualitative variables respectively. Kaplan Meier analysis was realized to determine renal survival according to RI value using the log-rank test. Multiple logistic regression was performed including variables with p < 0.20 in univariate analysis.

Results

Most patients had glomerulonephritis (82%). Median age was 46 years [21–87], eGFR 59 mL/min/ 1.73m2 [5–130], percentage of interstitial fibrosis 10% [0–90], glomerulosclerosis 13% [0–96] and RI 0.63 [0.31-1.00]. RI increased with age (r = 0.435, p = 0.0063), pulse pressure (r = 0.303, p = 0.022), renal atrophy (r = −0.275, p = 0.038) and renal dysfunction (r = −0.402, p = 0.0018). Patients with arterial intima/media ratio ≥ 1 (p = 0.032), interstitial fibrosis > 20% (p = 0.014) and renal function decline (p = 0.0023) had higher RI. Patients with baseline RI ≥ 0.65 had a poorer renal outcome than those with baseline RI < 0.65 (p = 0.0005). In multiple logistic regression, RI≥0.65 was associated with accelerated renal function decline independently of baseline eGFR and proteinuria/creatininuria ratio (OR=13.04 [1.984-85.727], p = 0.0075). Sensitivity, specificity, predictive positive and predictive negative values of RI ≥ 0.65 for renal function decline at 18 months were respectively 77%, 86%, 71% and 82%.

Conclusions

Our results suggest that RI ≥ 0.65 is associated with severe interstitial fibrosis and arteriosclerosis and renal function decline. Thus, RI may contribute to identify patients at high risk of ESRD who may benefit from nephroprotective treatments.

ABSTRACT

BACKGROUND

In the United States, public health insurance is available for nearly all persons with end-stage renal disease (ESRD). Little is known about the extent of health insurance coverage for persons with non-dialysis dependent chronic kidney disease (CKD).

OBJECTIVE

To describe patterns of health insurance coverage for adults with non-dialysis dependent CKD and to examine risk factors for progression of CKD to ESRD and management of hypertension among those lacking insurance.

DESIGN AND PARTICIPANTS

Cross-sectional analysis of data from a nationally representative sample of 16,148 US adults aged 20 years or older who participated in the National Health and Nutrition Examination Survey 1999-2006.

MEASUREMENTS

National prevalence estimates of health insurance coverage, ESRD risk factors, and treatment of hypertension.

MAIN RESULTS

An estimated 10.0% (95% CI, 8.3%-12.0%) of US adults with non-dialysis dependent CKD were uninsured, 60.9% (95% CI, 58.2%-63.7%) had private insurance and 28.7% (95% CI, 26.4%-31.1%) had public insurance alone. Uninsured persons with non-dialysis dependent CKD were more likely to be under the age of 50 (62.8% vs. 23.0%, < 0.001) and nonwhite (58.7%, vs. 21.8%, < 0.001) compared with their insured counterparts. Approximately two-thirds of uninsured adults with non-dialysis dependent CKD had at least one modifiable risk factor for CKD progression, including 57% with hypertension, 40% who were obese, 22% with diabetes, and 13% with overt albuminuria. In adjusted analyses, uninsured persons with non-dialysis dependent CKD were less likely to be treated for their hypertension (OR, 0.59; 95% CI, 0.40-0.85) and less likely to be receiving recommended therapy with angiotensin inhibitors (OR, 0.45; 95% CI, 0.26-0.77) compared with those with insurance coverage.

CONCLUSIONS

Uninsured persons with non-dialysis dependent CKD are at higher risk for progression to ESRD than their insured counterparts but are less likely to receive recommended interventions to slow disease progression. Lack of public health insurance for patients with non-dialysis dependent CKD may result in missed opportunities to slow disease progression and thereby reduce the public burden of ESRD.

Background:

Canada, akin to other developed nations, faces the growing challenges of end-stage renal disease (ESRD). Even with expanded donor criteria for renal transplantation (the treatment of choice for ESRD), the supply of kidneys is outpaced by the escalating demand. Remuneration for kidney donation is proscribed in Canada. Without an option of living-related transplantation (biological or emotional donors), patients often struggle with long waiting lists for deceased donor transplantation. Accordingly, many patients are now opting for more expedient avenues to obtaining a renal transplant. Through commercial organ retrieval programs, from living and deceased donors, patients are travelling outside Canada to have the procedure performed.

Methods:

Between September 2001 and July 2007, 10 patients (7 males, 3 females) underwent commercial renal transplantation outside Canada. We describe the clinical outcomes of these patients managed postoperatively at our single Canadian transplant centre.

Results:

Six living unrelated and 4 deceased donor renal transplantations were performed on these 10 patients (mean age 49.5 years). All procedures were performed in developing countries and the postoperative complications were subsequently treated at our centre. The mean post-transplant serum creatinine was 142 μmol/L. The average follow-up time was 29.8 months (range: 3 to 73 months). One patient required a transplant nephrectomy secondary to fungemia and subsequently died. One patient had a failed transplant and has currently resumed hemodialysis. Acute rejection was seen in 5 patients with 3 of these patients requiring re-initiation of hemodialysis. Only 1 patient had an uncomplicated course after surgery.

Discussion:

Despite the kidney trade being a milieu of corruption and commercialization, and the high risk of unconventional complications, patients returning to Canada after commercial renal transplantation are the new reality. Patients are often arriving without any documentation; therefore, timely, goal-directed therapy for surgical and infectious complications is frequently delayed because of the time taken to establish an accurate diagnosis. Refuting the existence of commercial renal transplantation may not be a practical solution; more consistent communication and documentation with transplant teams may be more pragmatic. In the current climate, patients considering the option of overseas commercial renal transplantation should be advised of the potential increased risks.

Background. Human urotensin II (UII) is a potent mammalian vasoconstrictor thought to be produced and cleared by the kidneys. Conflicting data exist regarding the relationship between UII concentrations, kidney function and blood pressure (BP). We measured the associations between kidney function [including end-stage renal disease (ESRD)] and levels of BP with plasma concentrations of UII.

Methods. Ninety-one subjects were enrolled. Thirty-one subjects had ESRD (undergoing haemodialysis), 30 subjects had chronic kidney disease (CKD) and 30 control subjects had no kidney disease. Plasma UII concentrations were measured by radioimmunoassay.

Results. Mean plasma UII concentrations were highest in controls, lower in subjects with ESRD and lowest in subjects with non-ESRD CKD (P < 0.0001). UII concentrations correlated negatively with serum creatinine (P = 0.0012) and CKD stage, and positively with creatinine clearance (P = 0.013). In ESRD subjects, plasma UII (P = 0.008) increased after dialysis, while SBP (P = 0.007), DBP (P = 0.009), serum creatinine (P < 0.0001) and serum urea nitrogen (P < 0.0001) decreased. UII concentrations were lower in patients with a history of hypertension (HTN) (P = 0.016). Age, race and gender did not appear to be associated with UII concentration. However, the distribution of African American race and male gender appear to be associated with increasing stages of chronic kidney disease.

Conclusions. These data suggest a potential vasodilatory role of UII in humans with kidney disease or hypertension. The reduction in UII levels in CKD also suggests either reduced production or greater clearance, or both, of UII.

Chronic kidney disease (CKD) is a serious threat to African-American public health. In this population CKD progresses to end-stage renal disease (ESRD) at quadruple the rate in Caucasians. Factors fueling progression to ESRD include diabetes and hypertension, which show high prevalences and accelerated renal damage in African- Americans, as well as possible nutritional, socioeconomic, and genetic factors. Anemia, a common and deleterious complication of CKD, is more prevalent and severe in African-American than Caucasian patients at each stage of the disease. Proactive management of diabetes, hypertension, anemia, and other complications throughout the course of CKD can prevent or delay disease progression and alleviate the burden of ESRD for the African-American community. Currently, African-Americans with CKD are less likely than Caucasian patients to receive anemia treatment before and after the onset of dialysis. Although African-Americans often require higher doses of erythropoiesis-stimulating agents, this may result from late treatment initiation, lower hemoglobin levels, or the presence of comorbidities such as diabetes and inflammation, although racial differences in response cannot be excluded. This review explores racial-specific challenges and potential solutions in renal anemia management to improve outcomes in African-American patients.

Background

The patient characteristics and mortality associated with autosomal dominant polycystic kidney disease (PKD) have not been characterized for a national sample of end stage renal disease (ESRD) patients on the renal transplant waiting list.

Methods

40,493 patients in the United States Renal Data System who were initiated on ESRD therapy between 1 April 1995 and 29 June 1999 and later enrolled on the renal transplant waiting list were analyzed in an historical cohort study of the relationship between hematocrit at the time of presentation to ESRD and survival (using Cox Regression) in patients with PKD as a cause of ESRD.

Results

Hematocrit levels at presentation to ESRD increased significantly over more recent years of the study. Hematocrit rose in parallel in patients with and without PKD, but patients with PKD had consistently higher hemoglobin. PKD was independently associated with higher hematocrit in multiple linear regression analysis (p < 0.0001). In logistic regression, higher hematocrit was independently associated with PKD. In Cox Regression analysis, PKD was associated with statistically significant improved survival both in comparison with diabetic (hazard ratio, 0.64, 95% CI 0.53–0.77, p < 0.001) and non-diabetic (HR 0.68, 95% CI 0.56–0.82, p = 0.001) ESRD patients, adjusted for all other factors.

Conclusions

Hematocrit at presentation to ESRD was significantly higher in patients with PKD compared with patients with other causes of ESRD. The survival advantage of PKD in ESRD persisted even adjusted for differences in hematocrit and in comparison with patients on the renal transplant waiting list.

Background

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).

Methods

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.

Results

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).

Conclusions

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.

The incidence of end-stage renal disease (ESRD) in the US is rising at an alarming rate, with the largest increase among African-American populations. The key risk factors for kidney disease are hypertension and diabetes, which are both becoming more prevalent in the US, and particularly in African Americans. Although African Americans make up 12.6% of the US population, the incidence of diabetes-related ESRD is four times higher than for whites, and the prevalence of ESRD due to hypertension is twice that of white patients. Approximately 30 to 40% of all patients with diabetes will develop nephropathy and many will progress to ESRD, necessitating dialysis or kidney transplantation. Recent studies in patients with type 2 diabetes indicate a significant delay in progression or development of diabetic nephropathy following blockade of the renin-angiotensin-aldosterone system with the use of angiotensin receptor antagonists. Early intervention in patients with hypertension is necessary to prevent kidney damage, and data from the African American Study of Kidney Disease and Hypertension suggest that angiotensin-converting enzyme inhibitors are effective in this population. Although African-American patients receiving hemodialysis appear to have increased survival compared with whites, racial factors and poor access to medical care contribute to the increased risk of kidney disease in minorities. A concerted effort is necessary to raise awareness in minority populations and provide strategies for prevention and early treatment thereby attenuating the increasing prevalence of kidney failure in these groups.

Context

High levels of the phosphate regulating hormone, fibroblast growth factor 23 (FGF23), associate with mortality in patients with end-stage renal disease (ESRD), but little is known about its relationship with adverse outcomes in the much larger population of patients with earlier stages of chronic kidney disease (CKD).

Objective

Evaluate FGF23 as a risk factor for adverse outcomes in patients with CKD.

Design, Setting and Participants

A prospective study of 3,879 participants with CKD stages 2 – 4 who enrolled in the Chronic Renal Insufficiency Cohort between June 2003 and September 2008.

Main Outcome Measures

All-cause mortality and ESRD.

Results

At enrollment, mean estimated glomerular filtration rate (eGFR) was 42.8 ± 13.5 ml/min/1.73m2, and median FGF23 was 145 (interquartile range [IQR] 96 – 239) reference units/ml (RU/ml). During a median follow-up of 3.5 (IQR 2.5 – 4.4) years, 266 participants died (20.3/1000 person-years) and 410 reached ESRD (33.0/1000 person-years). Higher FGF23 levels independently associated with a greater risk of death in adjusted analyses of FGF23 on a continuous scale (hazard ratio [HR] per SD of lnFGF23, 1.5; 95%CI 1.3 – 1.7) or in quartiles (quartile 1, reference; quartile 2, HR 1.3; 95%CI 0.8 – 2.2; quartile 3, HR 2.0; 95%CI 1.2 – 3.3; quartile 4, HR 3.0; 95%CI 1.8 – 5.1). FGF23 was not independently associated with ESRD in adjusted analyses of the entire cohort, however, the effect was modified by eGFR (P for interaction = 0.005), which was the strongest predictor for ESRD. FGF23 independently associated with significantly greater risk of ESRD among participants with eGFR 30 – 44 (HR 1.3 per SD of lnFGF23; 95%CI 1.04 – 1.6) and ≥ 45 (HR 1.7; 95%CI 1.1 – 2.4), but not < 30 ml/min/1.73m2.

Conclusion

Elevated FGF23 is an independent risk factor for ESRD in patients with relatively preserved kidney function and for mortality across the spectrum of CKD.