S. Sanoff

Positive association of renal insufficiency with agriculture employment and unregulated alcohol consumption in Nicaragua

Background and objectives: Endemic renal insufficiency (RI) of unknown etiology is a major public health issue with high mortality in the Pacific coastal regions of Central America. We studied RI in León and Chinandega, Nicaragua, evaluating associations with known risk factors and hypothesized exposures. Methods: A cross-sectional survey was conducted with assessment of medical, social, and occupational history and exposures in conjunction with measurement of serum creatinine. Cases were defined by an estimated glomerular filtration rate (eGFR) ≤60 mL/min/1.73 m2 using the modified four-variable Modification of Diet in Renal Disease (MDRD) study equation for non-African Americans. Logistic regression models controlling for known risk factors of kidney disease were used to evaluate associations between exposures and RI. Results: A total of 124 RI cases were compared to 873 persons without RI. Cases had no significant differences in the odds of having a systolic blood pressure (SBP) > 140 or diastolic blood pressure (DBP) > 90 mmHg, or in reporting diabetes. Agricultural labor was associated with RI (OR = 2.48, 95%CI: 1.59, 3.89, p < 0.0001). There was no association with agricultural non-field work (OR = 0.91, 95%CI: 0.60, 1.38, p = 0.65). Consumption of unregulated alcohol (“lija”) was associated with RI (OR = 2.10, 95%CI: 1.31, 3.39, p = 0.0023), as was drinking 5 L or more of water per day (OR = 3.59 vs. 1 L 95%CI: 1.52, 4.46, p = 0.0035). Conclusions: Agricultural field labor and lija consumption were associated with RI in this region. Water intake may also be important. Identifying specific risk factors for RI within these exposures, such as individual pesticides or lija ingredients, may facilitate prevention in a setting where dialysis and transplantation are limited.

Care of the Undocumented Immigrant in the United States With ESRD

The growth of the undocumented immigrant population in the United States has been explosive. The absence of a uniform policy regarding health care for this population has created a unique problem for nephrologists. How should provision of care for undocumented immigrants with end-stage renal disease be delivered and compensated? This problem is exacerbated by the multiple complex laws that govern delivery of and payment for care, as well as that state regulations vary widely and are not easily understood. Furthermore, the ethical and moral commitments of providers to ensure adequate and appropriate care for any patient whose life is at stake, irrespective of his or her immigration status, place nephrologists in a difficult position. This review focuses on the scope of this problem, relevant case law and legislation, current care and payment models, the response of nephrology groups, and ethical dilemmas inherent in caring for this vulnerable population. Recommendations for further study, including convening of a consensus conference, are discussed.

Outcomes in kidney transplant recipients from older living donors.

Background Previous studies demonstrate that graft survival from older living kidney donors (LD; age >60 years) is worse than younger LD but similar to deceased standard criteria donors (SCD). Limited sample size has precluded more detailed analyses of transplants from older LD. Methods Using the United Network for Organ Sharing database from 1994 to 2012, recipients were categorized by donor status: SCD, expanded criteria donor (ECD), or LD (by donor age: <60, 60–64, 65–69, ≥70 years). Adjusted models, controlling for donor and recipient risk factors, evaluated graft and recipient survivals. Results Of 250,827 kidney transplants during the study period, 92,646 were LD kidneys, with 4.5% of these recipients (n = 4,186) transplanted with older LD kidneys. The use of LD donors 60 years or older increased significantly from 3.6% in 1994 to 7.4% in 2011. Transplant recipients with older LD kidneys had significantly lower graft and overall survival compared to younger LD recipients. Compared to SCD recipients, graft survival was decreased in recipients with LD 70 years or older, but overall survival was similar. Older LD kidney recipients had better graft and overall survival than ECD recipients. Conclusions As use of older kidney donors increases, overall survival among kidney transplant recipients from older living donors was similar to or better than SCD recipients, better than ECD recipients, but worse than younger LD recipients. With increasing kidney donation from older adults to alleviate profound organ shortages, the use of older kidney donors appears to be an equivalent or beneficial alternative to awaiting deceased donor kidneys.

A population-based study of prevalence and risk factors of chronic kidney disease in León, Nicaragua

BackgroundRecent studies have shown an excess of chronic kidney disease (CKD) among younger adult males in the Pacific coastal region of Nicaragua and suggest a non-conventional CKD etiology in this region. These studies have been conducted in small, non-representative populations.ObjectivesWe conducted a large population-based cross-sectional study to estimate CKD prevalence in León, Nicaragua, and to evaluate the association between previously investigated risk factors and CKD.MethodsEstimated glomerular filtration rate, derived using the MDRD equation, was assessed to determine CKD status of 2275 León residents. Multivariable logistic regression was used to estimate adjusted prevalence odds ratios. León CKD prevalence was also standardized to the demographic distributions of the León Health and Demographic Surveillance System and the León 2005 Census.ResultsCKD prevalence was 9.1%; twice as high for males (13.8%) than females (5.8%). In addition to gender, older age, rural zone, lower education level, and self-reported high blood pressure, more years of agricultural work, lija (unregulated alcohol) consumption, and higher levels of daily water consumption were significantly associated with CKD. Notably, self-reported diabetes was associated with CKD in adjusted models for females but not males.ConclusionsOur findings are comparable to those found in regional studies and further support the hypothesis of a Mesoamerican Nephropathy.AbrégéContexteSelon de récentes études, il existerait une prévalence d’insuffisance rénale chronique (IRC) excessive chez les jeunes adultes de sexe masculin de la côte du Pacifique du Nicaragua. Ces études, qui ont été conduites sur des échantillons non représentatifs de la population, suggèrent une étiologie non classique de l’IRC dans cette région.Objectifs de l’étudeNous avons effectué une étude transversale portant sur un vaste échantillon de population, afin de pouvoir estimer la prévalence d’IRC dans la ville nicaraguéenne de León, d’une part, et évaluer la présence de liens entre l’IRC et certains facteurs de risque ayant été étudiés, d’autre part.MéthodePour déterminer le statut d’IRC de 2275 résidents de la ville de León, nous avons utilisé le débit de filtration glomérulaire estimé, selon l’équation du MDRD. Une régression logistique multivariée a été utilisée pour estimer les ratios de probabilité corrigés de prévalence. La prévalence d’IRC de León a également été normalisée sur la base de la distribution démographique du Health and Demographic Surveillance System de León et avec son recensement de 2005.RésultatsLa prévalence d’IRC était de 9,1%; elle était deux fois plus élevée chez les hommes (13,8%) que chez les femmes (5,8%). D’autres facteurs ont été liés de façon significative à l’IRC: la vieillesse, la vie rurale, un niveau d’éducation faible, une hypertension autodéclarée, plusieurs années de travail en agriculture, et la consommation de lija (alcool non contrôlé) et de grandes quantités d’eau. Le diabète autodéclaré était également lié à l’IRC dans les modèles ajustés chez les femmes, mais non chez les homm es.ConclusionsNos résultats sont comparables à ceux des études locales et supportent l’hypothèse de l’existence d’une néphropathie méso-américaine.

Impact of Acute Kidney Injury on Chronic Kidney Disease and Its Progression

Acute kidney injury (AKI) is a devastating clinical problem that affects a growing number of patients, especially elderly ones, and is associated with high morbidity and mortality. It was previously thought that patients who survive an episode of AKI recover renal function without further sequelae; however, recent population- based studies suggest that this may not be the case. New clinical studies suggest that a strikingly large percentage of patients who have AKI do not fully recover renal function or require permanent renal replacement therapy, and that this population has an important impact on the epidemiology of chronic kidney disease (CKD) and end-stage renal disease. These clinical studies verify animal studies that have established a link between AKI and CKD progression. Future clinical studies are underway to prospectively characterize the natural history of AKI and CKD progression and to identify predictive biomarkers.

Trends in Usage and Outcomes for Expanded Criteria Donor Kidney Transplantation in the United States Characterized by Kidney Donor Profile Index.

There has been increasing concern in the kidney transplant community about the declining use of expanded criteria donors (ECD) despite improvement in survival and quality of life. The recent introduction of the Kidney Donor Profile Index (KDPI), which provides a more granular characterization of donor quality, was expected to increase utilization of marginal kidneys and decrease the discard rates. However, trends and practice patterns of ECD kidney utilization on a national level based on donor organ quality as per KDPI are not well known. We, therefore, performed a trend analysis of all ECD recipients in the United Network for Organ Sharing (UNOS) registry between 2002 and 2012, after calculating the corresponding KDPI, to enable understanding the trends of usage and outcomes based on the KDPI characterization. High-risk recipient characteristics (diabetes, body mass index ≥30 kg/m2, hypertension, and age ≥60 years) increased over the period of the study (trend test p<0.001 for all). The proportion of ECD transplants increased from 18% in 2003 to a peak of 20.4% in 2008 and then declined thereafter to 17.3% in 2012. Using the KDPI >85% definition, the proportion increased from 9.4% in 2003 to a peak of 12.1% in 2008 and declined to 9.7% in 2012. Overall, although this represents a significant utilization of kidneys with KDPI >85% over time (p<0.001), recent years have seen a decline in usage, probably related to regulations imposed by Centers for Medicare & Medicaid Services (CMS). When comparing the hazards of graft failure by KDPI, ECD kidneys with KDPI >85% have a slightly lower risk of graft failure compared to standard criteria donor (SCD) kidneys with KDPI >85%, with a hazard ratio (HR) of 0.95, a confidence interval (CI) of 0.94-0.96, and statistical significance of p<0.001. This indicates that some SCD kidneys may actually have a lower estimated quality, with a higher Kidney Donor Risk Index (KDRI), than some ECDs. The incidence of delayed graft function (DGF) in ECD recipients has significantly decreased over time from 35.2% in 2003 to 29.6% in 2011 (p=0.007), probably related to better understanding of the donor risk profile along with increased use of hypothermic machine perfusion and pretransplant biopsy to aid in optimal allograft selection. The recent decline in transplantation of KDPI >85% kidneys probably reflects risk-averse transplant center behavior. Whether discard of discordant SCD kidneys with KDPI >85% has contributed to this decline remains to be studied.

Therapeutic apheresis in kidney transplantation: A review of renal transplant immunobiology and current interventions with apheresis medicine

Transplantation is the treatment of choice for end stage renal disease. Kidney transplants convey both a significant survival advantage to the individual recipient as well as cost savings to the medical system. Circulating alloantibodies directed against donor human leukocyte antigens and blood group antigens are fairly common among potential recipients. They are known to injure allografts, shorten allograft survival, and limit access to kidney transplantation. Hence, screening for pretransplant alloantibodies using complement dependent cytotoxic cross‐matching and more sensitive techniques such as the solid phase assays, have become routine in an attempt to avoid incompatible donor–recipient pairs and risk stratify those with donor specific antibodies (DSA). By removing harmful antibodies, therapeutic apheresis (TA) has become a critical tool for improving access to transplantation in cases where the immunologic risk had previously been considered unacceptable. It has also allowed us to transplant across the barrier of ABO blood group incompatibility and expand the pool of donors with reasonable success. Furthermore, it is an important tool in the treatment of antibody‐mediated rejection. Advanced apheresis technologies, such as immunoadsorption, and the use of TA in combination with innovative paired‐donor exchange programs, offer the potential to further improve access and outcomes, minimizing the short comings of one single form of therapy alone. J. Clin. Apheresis 28:56–63, 2013.

The Role of Therapeutic Apheresis in High Immunologic Risk Renal Transplantation: A Review of Current Trends

Immunologic sensitization, defined by the presence of antibodies directed against donor human leukocyte antigen (or so called donor‐specific antibodies [DSA]), is common among those awaiting kidney transplantation, and is associated with worse outcomes following transplant. Existing DSA have historically been screened for pretransplant using complement‐dependent cytotoxic crossmatching and their risk circumnavigated through policies that prohibit transplants between incompatible donor–recipient pairs. This risk avoidance strategy maximizes outcomes following transplant, but at the expense of limiting access to transplant for sensitized individuals. Over the last decade, the field of kidney transplantation has moved to actively modify the risks posed by DSA, rather than to simply avoid them. More sensitive detection methods have provided detailed immunologic risk stratification of potential donor–recipient pairs. Desensitization protocols, in which therapeutic aphaeresis plays a central role, have been used to reduce the potential harms posed by DSA. More recently, desensitization and paired donor exchange programs have been used in combination to expand transplantation to highly sensitized patients with incompatible living donors. It is likely that this combination of risk mitigation and avoidance strategies will be used together more often to both maximize individuals’ access to transplant, and optimize patient and graft outcomes.

Therapeutic apheresis before and after kidney transplantation

Kidney transplantation is considered the treatment of choice for most individuals with end‐stage kidney disease, as well as the most cost‐effective renal replacement therapy for the health care system that serves them. Immunologic sensitization, defined by the presence of antibodies directed against foreign HLA (or so called, donor specific antibodies, or DSA), is a significant barrier to kidney transplantation. Further, the presence of DSA is associated with an increase in the incidence of antibody‐mediated rejection and decreased graft survival following transplantation. Therapeutic plasma exchange, an extracorporeal therapy directed at removing plasma proteins, including DSA, has proven to be an important part of a comprehensive strategy to minimize the effect of sensitization before, and following kidney transplantation. As such, it offers the promise of increasing access to transplantation, as well as improving outcomes following transplantation. In this concise narrative review, we describe more specifically the benefits of kidney transplantation, the epidemiology of kidney transplantation in the United States, the clinical significance of anti‐HLA antibodies, and the evidence supporting a role for therapeutic plasma exchange before and after kidney transplantation. J. Clin. Apheresis, 2011.

Lymphocyte depletion and risk of acute rejection in renal transplant recipients at increased risk for delayed graft function

Delayed graft function (DGF) is a risk factor for acute rejection (AR) in renal transplant recipients, and KDIGO guidelines suggest use of lymphocyte‐depletion induction when DGF is anticipated. We analyzed the United Network for Organ Sharing/Organ Procurement and Transplantation Network (UNOS/OPTN) database to assess the impact of induction immunosuppression on the risk of AR in deceased kidney recipients based on pretransplant risk of DGF using a validated model. Recipients were categorized into 4 groups based upon the induction immunosuppression: (1) Rabbit anti‐thymocyte globulin (rATG); (2) Alemtuzumab (C1H); (3) IL2‐receptor antagonists (IL2‐RA; basiliximab or daclizumab), and (4) No antibody induction. The primary endpoint for analysis was a composite endpoint of treated AR or graft failure by 1‐year posttransplantation. Compared to no antibody induction, rATG and C1H had consistently lower adjusted odds of the composite endpoint across all risk strata for DGF risk, whereas IL2‐Ra was associated with increased adjusted odds of the composite endpoint with increasing DGF risk. When the induction agents were compared, rATG and C1H were associated with decreasing adjusted odds for the composite endpoint with increasing risk of DGF, especially at the higher risk spectrum of DGF. Consideration must be given to use of lymphocyte‐depletion induction when the anticipated risk of DGF is increased.