Evaluation of Low- Versus High-dose Valganciclovir for Prevention of Cytomegalovirus Disease in High-risk Renal Transplant Recipients

Transplantation - Most Popular Articles Evaluation of Low- Versus High-dose Valganciclovir for Prevention of Cytomegalovirus Disease in High-risk Renal Transplant Recipients

Background: Despite proven efficacy of prolonged cytomegalovirus (CMV) prophylaxis using valganciclovir 900 mg/day, some centers use 450 mg/day due to reported success and cost savings. This multicenter, retrospective study compared the efficacy and safety of 6 months of low-dose versus high-dose valganciclovir prophylaxis in high-risk, donor-positive/recipient-negative, renal transplant recipients (RTR). Methods: Two hundred thirty-seven high-risk RTR (low-dose group = valganciclovir 450 mg/day [n = 130]; high-dose group = valganciclovir 900 mg/day [n = s7]) were evaluated for 1-year CMV disease prevalence. Breakthrough CMV, resistant CMV, biopsy-proven acute rejection (BPAR), graft loss, opportunistic infections (OI), new-onset diabetes after transplantation (NODAT), premature valganciclovir discontinuation, renal function and myelosuppression were also assessed. Results: Patient demographics and transplant characteristics were comparable. Induction and maintenance immunosuppression were similar, except for more early steroid withdrawal in the high-dose group. Similar proportions of patients developed CMV disease (14.6% vs 24.3%; P = 0.068); however, controlling CMV risk factor differences through multivariate logistic regression revealed significantly lower CMV disease in the low-dose group (P = 0.02; odds ratio, 0.432, 95% confidence interval, 0.211–0.887). Breakthrough and resistant CMV occurred at similar frequencies. There was no difference in renal function or rates of biopsy-proven acute rejection, graft loss, opportunistic infections, or new-onset diabetes after transplantation. The high-dose group had significantly lower mean white blood cell counts at months 5 and 6; however, premature valganciclovir discontinuation rates were similar. Conclusions: Low-dose and high-dose valganciclovir regimens provide similar efficacy in preventing CMV disease in high-risk RTR, with a reduced incidence of leukopenia associated with the low-dose regimen and no difference in resistant CMV. Low-dose valganciclovir may provide a significant cost avoidance benefit.


http://journals.lww.com/transplantjournal/Fulltext/2015/07000/Evaluation_of_Low__Versus_High_dose_Valganciclovir.34.aspx

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Alberto Reino Buelvas 

Médico Internista Nefrólogo

Recurrent Membranoproliferative Glomerulonephritis Type I After Kidney Transplantation: A 17-Year Single-Center Experience

Transplantation - Current Issue Recurrent Membranoproliferative Glomerulonephritis Type I After Kidney Transplantation: A 17-Year Single-Center Experience

Background: Most previously published studies of patients with membranoproliferative glomerulonephritis type I are small or have short follow-up period. We report the outcome of a fairly large cohort of patients followed up for nearly 10 years. Methods: Retrospective cohort study. Graft survival, recurrence rate and risk factors for recurrence were analyzed for 43 patients transplanted between the years 1995 and 2012. Results: At a mean overall follow-up of 118±61 months (median, 127.8; range, 4.9–217), 12 patients lost their graft (28%). Death-censored actuarial 15-year graft survival rate was 56%. Membranoproliferative glomerulonephritis recurred in eight patients (19%) at a median time of 15.4 months (range, 4.4–70 months). Recurrence led to graft loss in seven patients (88%) within a median of 11.6 months (range, 1.3–54 months) from diagnosis. Median graft survival was 30.5 months for recurrence (range, 7–86). Actuarial 15-year graft survival was 71% for nonrecurrent. The risk for recurrence was higher for patients with human leukocyte antigen (HLA) B49 (odds ratio, 16.9; 95% confidence interval, 1.1–246; P=0.038) and HLA DR4 (odds ratio, 15.9; 95% confidence interval, 1.07–237; P=0.044) alleles. A trend toward increased risk was found with shorter duration of dialysis before transplantation. Four of 16 (25%) living-related versus none of the living-unrelated donors' recipients recurred. The HLA B49, acute tubular necrosis after transplantation, previous transplantations, and Arab origin were all associated with decreased graft and patient survival. Conclusion: Patients without recurrence in the first years should expect an excellent graft survival. Nonrelated living donors should be preferred. The HLA B49 and DR4 alleles may increase the risk for recurrence.


http://journals.lww.com/transplantjournal/Fulltext/2015/06000/Recurrent_Membranoproliferative_Glomerulonephritis.15.aspx

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Alberto Reino Buelvas

Rates and Determinants of Progression to Graft Failure in Kidney Allograft Recipients With De Novo Donor-Specific Antibody

AJT - Early Rates and Determinants of Progression to Graft Failure in Kidney Allograft Recipients With De Novo Donor-Specific Antibody

Understanding rates and determinants of clinical pathologic progression for recipients with de novo donor-specific antibody (dnDSA), especially subclinical dnDSA, may identify surrogate endpoints and inform clinical trial design. A consecutive cohort of 508 renal transplant recipients (n = 64 with dnDSA) was studied. Recipients (n = 388) without dnDSA or dysfunction had an eGFR decline of −0.65 mL/min/1.73 m²/year. In recipients with dnDSA, the rate eGFR decline was significantly increased prior to dnDSA onset (−2.89 vs. −0.65 mL/min/1.73 m²/year, p < 0.0001) and accelerated post-dnDSA (−3.63 vs. −2.89 mL/min/1.73 m²/year, p < 0.0001), suggesting that dnDSA is both a marker and contributor to ongoing alloimmunity. Time to 50% post-dnDSA graft loss was longer in recipients with subclinical versus a clinical dnDSA phenotype (8.3 vs. 3.3 years, p < 0.0001). Analysis of 1091 allograft biopsies found that dnDSA and time independently predicted chronic glomerulopathy (cg), but not interstitial fibrosis and tubular atrophy (IFTA). Early T cell–mediated rejection, nonadherence, and time were multivariate predictors of IFTA. Independent risk factors for post-dnDSA graft survival available prior to, or at the time of, dnDSA detection were delayed graft function, nonadherence, dnDSA mean fluorescence intensity sum score, tubulitis, and cg. Ultimately, dnDSA is part of a continuum of mixed alloimmune-mediated injury, which requires solutions targeting T and B cells.

http://onlinelibrary.wiley.com/resolve/doi?DOI=10.1111%2Fajt.13347

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Alberto Reino Buelvas

Paricalcitol for Secondary Hyperparathyroidism in Renal Transplantation

Journal of the American Society of Nephrology current issue Paricalcitol for Secondary Hyperparathyroidism in Renal Transplantation

Secondary hyperparathyroidism contributes to post-transplant CKD mineral and bone disorder. Paricalcitol, a selective vitamin D receptor activator, decreased serum parathyroid hormone levels and proteinuria in patients with secondary hyperparathyroidism. This single-center, prospective, randomized, crossover, open-label study compared the effect of 6-month treatment with paricalcitol (1 μg/d for 3 months and then uptitrated to 2 µg/d if tolerated) or nonparicalcitol therapy on serum parathyroid hormone levels (primary outcome), mineral metabolism, and proteinuria in 43 consenting recipients of renal transplants with secondary hyperparathyroidism. Participants were randomized 1:1 according to a computer-generated sequence. Compared with baseline, median (interquartile range) serum parathyroid hormone levels significantly declined on paricalcitol from 115.6 (94.8–152.0) to 63.3 (52.0–79.7) pg/ml (P<0.001) but not on nonparicalcitol therapy. At 6 months, levels significantly differed between treatments (P<0.001 by analysis of covariance). Serum bone-specific alkaline phosphatase and osteocalcin decreased on paricalcitol therapy only and significantly differed between treatments at 6 months (P<0.001 for all comparisons). At 6 months, urinary deoxypyridinoline-to-creatinine ratio and 24-hour proteinuria level decreased only on paricalcitol (P<0.05). L3 and L4 vertebral mineral bone density, assessed by dual-energy x-ray absorption, significantly improved with paricalcitol at 6 months (P<0.05 for both densities). Paricalcitol was well tolerated. Overall, 6-month paricalcitol supplementation reduced parathyroid hormone levels and proteinuria, attenuated bone remodeling and mineral loss, and reduced eGFR in renal transplant recipients with secondary hyperparathyroidism. Long-term studies are needed to monitor directly measured GFR, ensure that the bone remodeling and mineral effects are sustained, and determine if the reduction in proteinuria improves renal and cardiovascular outcomes.

http://jasn.asnjournals.org/cgi/content/short/26/5/1205?rss=1

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Alberto Reino Buelvas

Metformin Use in Type 2 Diabetes Mellitus With CKD: Is It Time to Liberalize Dosing Recommendations?

American Journal of Kidney Diseases Metformin Use in Type 2 Diabetes Mellitus With CKD: Is It Time to Liberalize Dosing Recommendations?

Metformin is a very effective drug for type 2 diabetes mellitus (T2DM) with relatively few side effects1 and has other potential benefits, such as lowering of cardiovascular risk2,3 and possible lowering of cancer risk.4 However, there is concern that metformin may increase the risk of lactic acidosis in people with chronic kidney disease (CKD). Considering the number of people with CKD and T2DM,5,6 there are potentially millions of people who are not currently taking metformin who might benefit from this medication.


http://www.ajkd.org/article/S0272-6386(15)00611-3/abstract?rss=yes

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Alberto Reino Buelvas 

Médico Internista Nefrólogo

Hypomagnesaemia in kidney transplantation

Transplantation Reviews Hypomagnesaemia in kidney transplantation

In the era of calcineurin inhibitors, hypomagnesaemia is a very common finding in kidney transplant recipients. Especially the first weeks after transplantation it is the rule rather than the exception. Hypomagnesaemia or low magnesium intake have been associated with a higher mortality or more cardiovascular events in the general population, but this association has never been explored in kidney transplant recipients, despite their increased cardiovascular risk. Kidney transplant recipients with pre- or post-transplant hypomagnesaemia seem to have an aberrant glucose metabolism and develop diabetes mellitus more frequently.


http://www.transplantationreviews.com/article/S0955-470X(15)00036-1/abstract?rss=yes

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Alberto Reino Buelvas 

Médico Internista Nefrólogo