Correlation between Dt/V derived from ionic dialysance and blood-driven Kt/V of urea in African-American hemodialysis patients, based on body weight and ultrafiltration volume.

BACKGROUND: The Dt/V obtained by using ionic dialysance (D) as a surrogate for urea clearance (K) is a well-validated adjunct measure of hemodialysis adequacy, with a variable level of correlation with urea-based Kt/V. However, this correlation has not been examined based on patients' body size and ultrafiltration (UF) volume during the dialysis session. METHODS: Simultaneous evaluations of online Dt/V and single-pool variable-volume urea Kt/V were made. Patients were categorized into three subgroups based on their weight (<60, 60-80 and ≥80 kg), body mass index (<25, 25-30 and >30 kg/m2) and UF volume (<1.5, 1.5-3 and >3 L). The correlation between Dt/V and Kt/V was evaluated for the entire cohort per dialysis session in each subgroup. RESULTS: Mean Kt/V was greater than the mean Dt/V (1.72 versus 1.50, P < 0.001), with an overall correlation r value of 0.602. This correlation was stronger in the medium weight group versus lower and higher weights. The correlation between Dt/V and Kt/V was inversely related to the UF volume (r = 0.698, 0.621 and 0.558 for those with UF volume of <1.5, 1.5-3.0 and >3 L, respectively). A total of 99.3% of patients with Dt/V of >1.2 also had Kt/V >1.2 and 9.5% of those with Dt/V <1.2 had their Kt/V <1.2. CONCLUSIONS: There is a moderate degree of correlation between Dt/V and Kt/V in African-American hemodialysis patients, which is impacted by body size and UF volume. A Dt/V of >1.2 strongly predicts adequate dialysis as defined by Kt/V of >1.2.

Preliminary experience with cinacalcet use in persistent secondary hyperparathyroidism after kidney transplantation.

BACKGROUND: There is limited experience with the use of cinacalcet in the treatment of persistent secondary hyperparathyroidism after kidney transplantation. METHODS: We retrospectively analyzed our experience in 18 renal allograft recipients who initiated cinacalcet therapy from 1 month to 23 years (median 3 years) posttransplantation and were maintained on the drug for 6 months. The daily dose was titrated from 30 mg up to a maximum of 180 mg to achieve a reduction in serum intact parathyroid hormone (PTH) levels. RESULTS: Sustainable, significant decreases in mean calcium and alkaline phosphatase were noted at 1 month and intact PTH by 3 months, with 50% of patients achieving at least a 30% drop in PTH levels at 6 months. Serum phosphorous increased at 6 months, whereas urine N-telopeptides decreased. There were no significant changes in serum osteocalcin, albumin, and hemoglobin levels. We did not observe a tachyphylaxis phenomenon. Two patients reported occasional nausea, but did not require medication discontinuation. Estimated glomerular filtration rate did decrease progressively over the 6-month period. CONCLUSION: Cinacalcet appears to be an effective drug for the treatment of posttransplant hypercalcemia due to persistent secondary hyperparathyroidism. Further studies with more patients and longer follow-up will be needed to better elucidate the efficacy/safety profile for this agent, particularly with regard to long-term bone histology and renal outcomes.

Case report: recurrent heart failure with preserved ejection fraction but markedly elevated BNP in a 51-year-old female on hemodialysis with oversized AV fistula.

We hereby report a case that appeared to have had recurrent clinical heart failure secondary to high-output state due to oversized arteriovenous fistula. Patient started to have dyspnea on exertion approximately 4 months after the creation of the fistula, and subsequently had two episodes of heart failure exacerbation. On both occasions, she had normal left ventricular systolic function as demonstrated by echocardiogram. The shunt was estimated to be as large as 1.9 L/min. B-type natriuretic peptide (BNP) levels were markedly elevated. To our knowledge, this is the first case in which BNP level was reported and used in the diagnosis of high-output heart failure.

Induction therapy with basiliximab versus Thymoglobulin in African-American kidney transplant recipients.

BACKGROUND: It has been suggested that the use of antilymphocyte induction therapy in African-American (AA) renal transplant recipients reduces the risk of acute rejection (AR) and improves graft survival. It is not clear whether the efficacy of basiliximab (BSX) is different from that of Thymoglobulin (ATG) in this regard. METHODS: We retrospectively assessed the effect of induction therapy with BSX versus ATG in 88 AA renal allograft recipients receiving transplants at our center between July 2001 and June 2003 and followed for 19+/-7 months. All patients were maintained on mycophenolate mofetil, prednisone, and either tacrolimus or sirolimus. Study endpoints included patient and graft survival, graft function, and incidence of AR and cytomegalovirus infection. Regression models were used to evaluate the independent effect of each induction agent on these endpoints. RESULTS: Thirty-six patients received ATG, and 52 received BSX. The groups were comparable with regard to donor race and age, and recipient sex, body mass index, human leukocyte antigen (HLA) matching, and hepatitis C virus serostatus. The ATG group was younger, more likely to receive retransplant, had longer duration of end-stage renal disease and higher panel reactive antibody, and was less likely to receive live-donor organs. However, after adjusting for all these variables, graft outcomes, as well as renal function, were comparable between the two induction groups. We found that the degree of HLA mismatch, delayed graft function, and AR were the only significant predictors of graft loss. CONCLUSION: The results of our study suggest that the choice of induction agent may not have a major impact on graft outcomes in AA renal-allograft recipients.

Gabapentin-induced hypoglycemia in a long-term peritoneal dialysis patient.

An end-stage renal disease patient on long-term peritoneal dialysis was admitted with dizziness, fatigue, hypoglycemia, and hypotension. The hypotension resolved with intravenous normal saline, but the hypoglycemia persisted for 3 days despite an intravenous dextrose drip and discontinuation of gabapentin. The patient became normoglycemic on the fourth day of admission. None of the known causes for the hypoglycemia were identified except gabapentin, the dose of which was recently doubled 1 month before admission. Insulin and C-peptide levels were high during the hypoglycemic episode and returned to normal after discontinuation of gabapentin. The patient remains off gabapentin and has had no further episodes of hypoglycemia. To our knowledge, this is the first case of hypoglycemia induced by gabapentin.

Lipid abnormalities and renal disease: is dyslipidemia a predictor of progression of renal disease?

Dyslipidemia is a cardiovascular disease (CVD) risk factor that is associated with enhanced atherosclerosis and plaque instability. Renal insufficiency is associated with abnormalities in lipoprotein metabolism in both the early and the advanced stages of chronic renal failure. These include alterations in apolipoprotein A (apo A)- and B- containing lipoproteins, high-density lipoproteins, and triglycerides. In animal models, these alterations in lipid metabolism and action lead to macrophage activation and infiltration in the kidney with resultant tubulointerstitial and endothelial cell injury. Limited data in humans suggest that, in addition to contributing to CVD, dyslipidemia may be a risk factor for the progression of renal disease. The effects of dyslipidemia on the kidney are mainly observed in those with other risk factors for renal disease progression such as hypertension, diabetes, and proteinuria. Renal disease is a strong risk factor for CVD and African Americans have high rates of renal disease. Therefore, examining the effects of dyslipidemia on the development or progression or renal disease will be an important question for the Jackson Heart Study and is the topic of this review.

Predictive value of human leucocyte antigen epitope matching using HLAMatchmaker for graft outcomes in a predominantly African-American renal transplant cohort.

The HLAMatchmaker program is based on the donor/recipient comparison of the polymorphic triplet amino-acid sequences of the antibody-accessible regions on the human leucocyte antigen (HLA) molecule. The previous reports on its predictive value for renal allograft outcomes are conflicting. We conducted a retrospective study in a predominantly African-American (AA) cohort (N = 101, 94% AA). HLA typing was performed by molecular methods and triplet matching using HLAMatchmaker. Study end points included graft survival and incidence of acute rejection. The relationship between the number of triplet mismatches (TMM) and the degree of HLA antigen MM was evaluated using Pearson's correlation coefficient. Logistic regression models were used to examine the association between triplet matching and the study end points. Kaplan-Meier and Cox proportional hazard models were used for graft survival analysis. The strongest relationship between the number of TMM and HLA antigen MM was observed for HLA-DQ (r = 0.88). The association between triplet matching at HLA-A, -B, -DR and -DRw HLA loci and the study end points was not statistically significant. However, after grouping, the unadjusted estimates of graft survival for those with more than 10 Class I TMM were significantly worse than the others (p = 0.03). Adjusting for the effect of donor source, recipient characteristics and the immunosuppressive regimen did not change this association (hazard ratio = 0.2, confidence interval = 0.04-1.1). We conclude that triplet matching using HLAMatchmaker can provide useful prognostic information in kidney transplantation and that more than 10 donor/recipient Class I HLA TMM is predictive of worse graft outcome.

Sirolimus-induced angioedema.

Sirolimus (SRL) is a macrolide immunosuppressant that has gained widespread use in organ transplantation. Its full spectrum of side-effects is yet to be defined. We describe herein three cases of SRL-induced angioedema (AE) in African-American (AA) primary renal allograft recipients who received SRL in combination with mycophenolate mofetil and steroids. In two cases, AE manifested after SRL was restarted after a period of discontinuation. The third case presented upon initial exposure to the drug. None of the patients was receiving any drug that has been previously associated with AE. Complete resolution occurred only after SRL was withdrawn. AE has not recurred in any of the patients during a follow-up period of up to 21 months. We conclude that AE is a previously unrecognized adverse event associated with SRL use. Close monitoring for this side-effect, especially in AA patients, is warranted.

West Nile virus encephalitis: an emerging disease in renal transplant recipients.

West Nile virus (WNV) has emerged as an important cause of several outbreaks of febrile illness and encephalitis in North America over the past few years. The most common manifestation in symptomatic patients is a transient febrile illness. Neuroinvasive disease, that can be fatal, occurs most often in elderly and immunocompromised hosts. The role of this virus as a cause of meninoencephalitis in organ transplant recipients is becoming better recognized. We describe herein the clinical course of two renal allograft recipients who developed WNV encephalitis. One patient developed status epilepticus and eventually died, while the other had a full recovery. In both cases, the diagnosis was confirmed by detection of WNV-specific IgM in CSF or serum, with a delayed antibody response in one patient. This viral infection should be considered in all renal transplant recipients who present with a febrile illness associated with neurological symptoms.