Impact of Post-Transplantation Hypomagnesemia on Long-Term Graft and Patient Survival after Transplantation.

BACKGROUND: Post-transplant hypomagnesemia is commonly observed among patients prescribed calcineurin inhibitor (CNIs). METHODS: We conducted a retrospective single-center analysis (2000-2013, N = 726) to examine the association of hypomagnesemia with long-term patient and allograft outcomes in kidney transplant recipients. A median serum magnesium (Mg) level of all measured Mg levels from 1 month to 1 year posttransplant was calculated. RESULTS: For every increase in Mg of 0.1 mg/dL, the risk for either graft loss or death, overall mortality, and death with a functioning graft increased by 11%, 14%, and 12%, respectively (p < 0.01). In a multivariate model, patients with median Mg level ≥1.7 mg/dL had a reduced overall survival rate (HR 1.57, 95% CI: 1.04-2.38, p = 0.033) compared to those with median Mg level <1.7 mg/dL. This association was observed in subgroups of patients above 60 years old, in those who had a slow graft function (SGF) and in females. CONCLUSIONS: Posttransplant hypomagnesemia is associated with better patient and allograft survival up to 10 years posttransplant. This relationship remained significant after accounting for baseline allograft function, presence of SGF and CNI trough levels.

Can uric acid blood levels in renal transplant recipients predict allograft outcome?

BACKGROUND: Hyperuricemia is common after renal transplantation, especially in those receiving calcineurin inhibitors. Little, however, is known about the relationship between uric acid (UA) levels and allograft outcome. METHODS: We conducted a retrospective single-center analysis (N = 368) in order to assess UA blood levels post-transplant association with allograft outcome. For this study, a median serum UA level of all measured UA levels from 1 month to 1 year post renal transplantation was calculated. RESULTS: Patients were divided into 2 groups based on the median UA level measured between 1 and 12 months post-transplant. Those with median UA level ≥ 7 and ≥ 6 mg/dL (N = 164) versus median UA level < 7 and < 6 mg/dL for men and women respectively (N = 204) had lower GFR values at 1, 3 and 5 years posttransplant (mean GFR ± SD of 43.4 ± 20.6 and 58 ± 19.9 at 3 years post-transplant, p < 0.001). In multivariate models, UA levels were no longer significantly associated with renal allograft function. In a multivariate cox proportional hazard model, UA level was found to be independently associated with increased risk for death-censored graft loss (HR of 1.3, 95% CI 1.0-1.7, p < 0.05 for every increase of 1 mg/dL in UA level). CONCLUSION: Hyperuricemia was found to be associated with increased death- censored graft loss but not with allograft function. Increased UA levels were not found to be an independent predictor of long-term allograft function despite the known association of hyperuricemia with the progression of cardiovascular and renal disease.

Posttransplantation Hypomagnesemia as a Predictor of Better Graft Function after Transplantation.

BACKGROUND: Hypomagnesemia is frequently seen after transplantation and is particularly associated with the use of calcineurin inhibitors (CNIs). METHODS: We conducted a retrospective, single-center analysis (2000-2013, N = 726) to explore the relationship between hypomagnesemia and long-term allograft outcome in kidney transplant recipients. For this study, a median serum magnesium (Mg) level of all measured Mg levels from 1 month to 1 year after renal transplantation was calculated. RESULTS: For every increase in Mg by 0.1 mg/dL, the GFR decreased by 1.1 mL/min at 3 years posttransplant (p < 0.01) and by 1.5 mL/min at 5 years posttransplant. A median blood Mg level of ≥1.7 was found to be an independent predictor of a GFR <60 mL/min at 3 years posttransplant. The odds of having a GFR <60 mL/min 3 years posttransplant was almost 2-fold higher in the high Mg group than in the low Mg group. CONCLUSIONS: Hypomagnesemia from 1 to 12 months after renal transplantation is associated with a better allograft function up to 5 years posttransplant. This relationship was found to hold true after accounting for baseline allograft function and the presence of slow graft function.

The Survival Benefit of "Fistula First, Catheter Last" in Hemodialysis Is Primarily Due to Patient Factors.

Patients needing hemodialysis are advised to have arteriovenous fistulas rather than catheters because of significantly lower mortality rates. However, disparities in fistula placement raise the possibility that patient factors have a role in this apparent mortality benefit. We derived a cohort of 115,425 patients on incident hemodialysis ≥67 years old from the US Renal Data System with linked Medicare claims to identify the first predialysis vascular access placed. We compared mortality outcomes in patients initiating hemodialysis with a fistula placed first, a catheter after a fistula placed first failed, or a catheter placed first (n=90,517; reference group). Of 21,436 patients with a fistula placed first, 9794 initiated hemodialysis with that fistula, and 8230 initiated dialysis with a catheter after failed fistula placement. The fistula group had the lowest mortality over 58 months (hazard ratio, 0.50; 95% confidence interval, 0.48 to 0.52; P<0.001), with mortality rates at 6, 12, and 24 months after initiation of 9%, 17%, and 31%, respectively, compared with 32%, 46%, and 62%, respectively, in the catheter group. However, the group initiating hemodialysis with a catheter after failed fistula placement also had significantly lower mortality rates than the catheter group had over 58 months (hazard ratio, 0.66; 95% confidence interval, 0.64 to 0.68; P<0.001), with mortality rates of 15%, 25%, and 42% at 6, 12, and 24 months, respectively. Thus, patient factors affecting fistula placement, even when patients are hemodialyzed with a catheter instead, may explain at least two thirds of the mortality benefit observed in patients with a fistula.

Second vascular access after failure of the first fistula in the elderly
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BACKGROUND: In patients with failure of an initial arteriovenous fistula (AVF), a subsequent vascular access is needed before hemodialysis (HD) initiation. METHODS: To assess the optimal access strategy after a failed AVF, we linked data from the US Renal Data System with Medicare claims data identifying 21,436 patients ≥ 67 years old who started HD between January 1, 2005, and December 31, 2008, with an AVF placed as their first predialysis access. Of the 10,568 subjects whose AVF failed, 1,796 patients had an AVF placed as a second access predialysis (AVF2 group) and 399 patients had an arteriovenous graft placed as a second access predialysis (AVG2 group). Second access success was defined as HD initiation for the first HD session using this access avoiding need for a catheter. RESULTS: The mean age for AVF2 and AVG2 groups was 75.9 ± 6.0 and 75.9 ± 5.9 years with a significantly greater percentage of men and whites in the AVF2 group and women and blacks in the AVG2 group. Overall, 53% of AVF2 group initiated dialysis using AVF2, and 66% of AVG2 group started dialysis using AVG2 (p < 0.001). The following variables were found to be associated with AVF2 failure: female gender, peripheral vascular disease (PVD), interventional procedures, and the absence of pre-ESRD nephrology care. AVG2 failure was associated with white race, lower body mass index (BMI), and the absence of pre-ESRD (end-stage renal disease) nephrology care. CONCLUSION: Since the success rate to avoid the use of a catheter was significantly higher in the AVG2 group than in the AVF2 group, an AVG may be a preferable choice of second access in certain patients, especially in females, blacks and those with PVD.
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Arteriovenous fistula placement in the elderly: when is the optimal time?

Arteriovenous fistula (AVF) is the preferred vascular access for hemodialysis (HD). However, many AVFs fail before starting dialysis. To assess the optimal time for AVF placement in the elderly, we linked data from the US Renal Data System with Medicare claims data to identify 17,511 patients ≥67 years old on incident HD who started dialysis between January 1, 2005, and December 31, 2008, with an AVF placed as the first predialysis access. AVF success was defined as dialysis initiation using the AVF, with time between AVF placement and dialysis start as our primary variable of interest. The mean age was 76.1±6.0 years, and 58.3% of subjects were men. Overall, 54.9% of subjects initiated dialysis using an AVF, and 45.1% of subjects used a catheter or graft. The success rate increased as time from AVF creation to HD initiation increased from 1-3 months (odds ratio [OR], 0.49; 95% confidence interval [95% CI], 0.44 to 0.53) to 3-6 months (OR, 0.93; 95% CI, 0.85 to 1.02) to 6-9 months (OR, 0.99; 95% CI, 0.88 to 1.11) but stabilized after that time. Furthermore, the number of interventional access procedures increased over time starting at 1-3 months, with a mean of 0.64 procedures/patient for AVFs created 6-9 months predialysis compared with 0.72 for AVFs created >12 months predialysis (P<0.001). Although limited by the observational nature of this study, our results suggest that placing an AVF >6-9 months predialysis in the elderly may not associate with a better AVF success rate.

Fistula first is not always the best strategy for the elderly.

Whether placing a fistula first is the superior predialysis approach among octogenarians is unknown. We analyzed data from a cohort of 115,425 incident hemodialysis patients ≥67 years old derived from the US Renal Data System with linked Medicare claims, which allowed us to identify the first predialysis vascular access placed rather than the first access used. We used proportional hazard models to evaluate all-cause mortality outcomes based on first vascular access placed, considering the fistula group as the reference. In the study population, 21,436 patients had fistulas as the first predialysis access placed, 3472 had grafts, and 90,517 had catheters. Those patients with a catheter as the first predialysis access placed had significantly inferior survival compared with those patients with a fistula (HR=1.77; 95% CI=1.73 to 1.81; P<0.001). However, we did not detect a significant mortality difference between those patients with a graft as the first access placed and those patients with a fistula (HR=1.05; 95% CI=1.00 to 1.11; P=0.06). Analyzing mortality stratified by age groups, grafts as the first predialysis access placed had inferior mortality outcomes compared with fistulas for the 67 to ≤79-years age group (HR=1.10; 95% CI=1.02 to 1.17; P=0.007), but differences between these groups were not statistically significant for the 80 to ≤89- and the >90-years age groups. In conclusion, fistula first does not seem to be clearly superior to graft placement first in the elderly, because each strategy associates with similar mortality outcomes in octogenarians and nonagenarians.

The role of initial hemodialysis vascular access in the outcome of subsequent kidney transplantation.

The role of initial hemodialysis vascular access in the subsequent kidney transplant outcome is unclear. Study population was derived from the United States Renal Data System and included adult patients with end-stage renal disease who started HD 1/1/2005-9/1/2009 and subsequently received at least one kidney transplant. Primary outcome variables were death-censored graft loss and all-cause recipient mortality. Among the study population (n = 17 157), 12 428 (72.4%) patients were initiated on HD with a catheter, 4090 (23.8%) patients with an arterio-venous fistula (AVF), and 639 (13.7%) patients with an arterio-venous graft (AVG). The rate of death-censored kidney allograft loss in AVF and AVG groups was not significantly different from the catheter group (HR, 0.82; p = 0.07 and HR, 0.68; p = 0.13, respectively). All-cause mortality of patients initiated on HD with AVG (HR, 0.761; p = 0.21) was not significantly different compared to those with catheters. However, all-cause mortality in the AVF group was lower compared to patients initiated on HD with catheters (HR, 0.65; p = 0.001). AVF used at the initiation of HD was associated with lower rate of all-cause mortality after kidney transplantation compared to the catheter. The type of initial vascular access for hemodialysis was not associated with kidney allograft survival.

Access to renal transplantation in the diabetic population-effect of comorbidities and body mass index.

BACKGROUND: In this study, we hypothesized that higher level of comorbidity and greater body mass index (BMI) may mediate the association between diabetes and access to transplantation. METHODS: We used data from the United States Renal Data System (01/01/2000-24/09/2007; n = 619,151). We analyzed two outcomes using Cox model: (i) time to being placed on the waiting list or transplantation without being listed and (ii) time to transplantation after being listed. Two primary Cox models were developed based on different levels of adjustment. RESULTS: In Cox models adjusted for a priori defined potential confounders, history of diabetes was associated with reduced transplant access (compared with non-diabetic population) - both for wait-listing/transplant without being listed (hazard ratio, HR = 0.80, p < 0.001) and for transplant after being listed (HR = 0.72, p < 0.001). In Cox models adjusted for BMI and comorbidity index along with the potential confounders, history of diabetes was associated with shorter time to wait-listing or transplantation without being listed (HR = 1.07, p < 0.001), and there was no significant difference in time to transplantation after being listed (HR = 1.01, p = 0.42). CONCLUSION: We demonstrated that higher level of comorbidity and greater BMI mediate the association between diabetes and reduced access to transplantation.

Education is associated with reduction in racial disparities in kidney transplant outcome.

In this study, we hypothesized that higher level of education might be associated with reduced racial disparities in renal transplantation outcomes. We used data from the United States Renal Data System (September 1, 1990-September 1, 2007) (n=79,223) and analyzed two outcomes, graft loss and recipient mortality, using Cox models. Compared with whites, African Americans had increased risk of graft failure (HR, 1.48; p<0.001) and recipient mortality (HR, 1.06; p=0.004). Compared with recipients who graduated from college, all other education groups had inferior graft survival. Specifically, compared with college-graduated individuals, African Americans who never finished high school had the highest risk of graft failure (HR, 1.45; p<0.001), followed by high school graduates (HR, 1.27; p<0.001) and those with some college education (HR, 1.18; p<0.001). A similar trend was observed in whites. In African Americans (compared with whites), the highest risk of graft failure was associated with individuals who did not complete high school (HR, 1.96; p<0.001) followed by high school graduates (HR, 1.47; p<0.001), individuals with some college education (HR, 1.45; p<0.001), and college graduates (HR, 1.39; p<0.001). A similar trend was observed with recipient mortality. In sum, higher education was associated with reduced racial disparities in graft and recipient survival.

Geographic disparities in arteriovenous fistula placement in patients approaching hemodialysis in the United States.

Arteriovenous fistula (AVF) is the preferred vascular access for hemodialysis (HD). Several factors associated with AVF placement have been identified (e.g., age, sex, race, comorbidities). We hypothesized that geographic location of patient residence might be associated with the probability of AVF placement as the initial access. We used the data from the United States Renal Data System (USRDS) database (2005-2008) linked to Medicare claims (2003-2008). Logistic regression was used to estimate specific characteristics of population associated with the AVF as first access placed or attempted for HD initiation. Our primary variable of interest was the geographic location, and the multivariate model was adjusted for age, sex, race, body mass index, primary cause of end-stage renal disease (ESRD), duration of pre-ESRD nephrology care, comorbidities, employment status, substance abuse, and income. Geographic location was determined using the data collected by the RUCA project and divided population into metropolitan, micropolitan, and rural categories. Patients (n = 111,953) identified from the USRDS database with linked Medicare claims were examined. Rates of fistula placement in the metropolitan, micropolitan, and rural population were 18.5%, 22.4%, and 21.6%, respectively. In comparison, patients who received catheter as the first access were 81.5%, 77.6% and 78.4%, respectively. The odds ratio of AVF placement as a first HD access in the rural and metropolitan population compared with the micropolitan population were 0.96 (0.90-1.03; P = 0.26) and 0.80 (0.76-0.84; P < 0.001), respectively. Our results indicate the presence of geographic disparities in AVF placement with decreased rates of AVF as the first access created in the metropolitan (but not rural) populations compared with the micropolitan communities.

Disparities in arteriovenous fistula placement in older hemodialysis patients.

The benefits of an arteriovenous fistula (AVF) as the preferred vascular access for hemodialysis have been clearly demonstrated. However, only about 20% of patients in the United States initiate hemodialysis with an AVF. In this study, we assessed whether disparities exist in the type of first hemodialysis access placed prior to dialysis start (rather than that used at dialysis initiation), to detect whether certain disadvantaged groups might have lower likelihood of AVF placement. Study cohort of 118,767 incident hemodialysis patients ≥67 years of age (1/2005-12/2008) derived from the United States Renal Data System was linked with Medicare claims data to identify the type of initial access placed predialysis. We used logistic regression model with outcome being the initial predialysis placement of an AVF as opposed to an arteriovenous graft or a central venous catheter. Increasing age, female sex, black race, lower body mass index, urban location, certain comorbidities, and shorter pre-end-stage renal disease nephrology care are all associated with a significantly lower likelihood of AVF placement as initial access predialysis. Our study suggests the presence of significant disparities in the placement of an AVF as initial hemodialysis vascular access. We suggest that additional attention should be paid to these patient groups to improve disparities by patient education, earlier referral, and close follow-up.

Case report on renal failure reversal in lambda chain multiple myeloma with bortezomib and dexamethasone.

Renal failure (RF) reversal in multiple myeloma (MM) is associated with an improved prognosis. Light chain myeloma, serum creatinine (SCr) > 4 mg/dL, extensive proteinuria, early infections, and certain renal biopsy findings are associated with lower rates of RF reversal. Our patient is a 67-year-old female with multiple poor prognostic factors for RF reversal who demonstrated a rapid renal response with bortezomib and dexamethasone (BD) regimen. She presented initially with altered mental status. On exam, she appeared lethargic and dehydrated and had generalized tenderness. She had been taking ibuprofen as needed for pain for a few weeks. Labs showed a white cell count-18,900/µL with no bandemia, hemoglobin 10.8 gm/dL, potassium-6.7 mEq/L, bicarbonate-15 mEq/L, blood urea nitrogen-62 mg/dL, SCr-5.6 mg/dL (baseline: 1.10), and corrected calcium-11.8 mg/dL. A rapid flu test was positive. Imaging studies were unremarkable. Her EKG showed sinus tachycardia and her urinalysis was unremarkable. The unexplained RF in an elderly individual in conjunction with hypercalcemia and anemia prompted a MM work-up; eventually, lambda variant MM was diagnosed. An immediate (4 days) renal response defined as 50% reduction in SCr was noticed after initiation of the BD regimen.

Factors predicting failure of AV "fistula first" policy in the elderly.

An arteriovenous fistula (AVF) is the preferential hemodialysis (HD) access. The goal of this study was to identify factors associated with pre-dialysis AVF failure in an elderly HD population. We used United States Renal Data System + Medicare claims data to identify patients ≥ 67 years old who had an AVF as their initial vascular access placed pre-dialysis. Failure of the AVF to be used for initial HD, was used as the outcome. Logistic regression model was used to identify factors associated with AVF failure. The study cohort consisted of 20,360 subjects (76.2 ± 6.02 year old, 58.5% men). Forty-eight percent of patients initiated dialysis using an AVF, while 52% used a catheter or an AVG. The following variables found to be associated with AVF failure when an AVF was created at least 4 months pre-HD initiation: older age (odds ratio [OR] 1.01; 95% confidence interval [CI] 1.00-1.02), female gender (OR 1.69; 95% CI 1.55-1.83), black race (OR 1.41; 95% CI 1.26-1.58), history of diabetes (OR 1.22; 95% CI 1.06-1.39), cardiac failure (OR 1.26; 95% CI 1.15-1.37), and shorter duration of pre-end-stage renal disease (ESRD) nephrology care (OR for a nephrology care of less than 6 months prior to ESRD of 1.22 compared with a pre-ESRD nephrology follow up of more than 12 months; 95% CI 1.07-1.38). OR for AVF failure for the entire cohort showed similar findings. In an elderly HD population, there is an association of older age, female gender, black race, diabetes, cardiac failure and shorter pre-ESRD nephrology care with predialysis AVF failure.

Social adaptability index predicts overall mortality in patients with diabetes.

BACKGROUND: A quantifiable assessment of socioeconomic status and its bearing on clinical outcome in patients with diabetes is lacking. The social adaptability index (SAI) has previously been validated in the general population and in patients with chronic kidney disease, including those on dialysis and with kidney transplant. We hypothesize that SAI could be used in diabetes practice to identify a disadvantaged population at risk for inferior outcomes. METHODS: The NHANES-3 database of patients who have diabetes was analyzed. The association of the SAI (calculated as the linear combination of indicators of education status, employment, income, marital status, and substance abuse) with patient survival was evaluated using Cox model. RESULTS: The study population consisted of 1634 subjects with diabetes mellitus with mean age of 61.9±15.3 years; 40.9% males; 38.5% white, 27.7% African American, and 31.3% Mexican American. The highest SAI was in whites (6.9±2.5), followed by Mexican Americans (6.5±2.3), and then African Americans (6.1±2.6) (ANOVA, P<.001). SAI was higher in subjects living in metropolitan areas (6.8±2.6) compared to the rural population (6.3±2.4) (T test, P<.001). Also, SAI was greater in males (7.1±2.4) than in females (6.1±2.4) (T test, P<.001). SAI had significant association with survival (hazard ratio 0.9, P<.001) in the entire study population and in most of the subgroups (divided by race, sex, and urban/rural location). Furthermore, SAI divided into tertiles (≤5, 6 to 8, >8) demonstrated a significant and "dose-dependent" association with survival. CONCLUSION: Social adaptability index is associated with mortality in the diabetic population and is useful in identifying individuals who are at risk for inferior outcomes.