Carfilzomib: A cause of drug associated thrombotic microangiopathy.

Carfilzomib is a selective proteosome inhibitor approved for treatment of relapsed and refractory multiple myeloma. Recent reports have linked exposure to carfilzomib with development of thrombotic microangiopathy (TMA). We describe two cases of biopsy proven thrombotic microangiopathy that occurred after the initiation of carfilzomib (dosed at 32 mg/m(2) and 23 mg/m(2), respectively) for relapsed multiple myeloma. Both patients were managed with discontinuation of the drug, therapeutic plasma exchange (TPE) and supportive care. Hemoglobin, platelets and renal function did not improve with TPE. TMA resolved with creatinine returning to baseline several weeks after discontinuation of the drug. The outcomes suggest that TPE is not beneficial for treating carfilzomib-induced TMA.

Cardiorespiratory Fitness (Peak Oxygen Uptake): Safe and Effective Measure for Cardiovascular Screening Before Kidney Transplant.

BACKGROUND: Significant heterogeneity exists in practice patterns and algorithms used for cardiac screening before kidney transplant. Cardiorespiratory fitness, as measured by peak oxygen uptake (VO2peak), is an established validated predictor of future cardiovascular morbidity and mortality in both healthy and diseased populations. The literature supports its use among asymptomatic patients in abrogating the need for further cardiac testing. METHODS AND RESULTS: We outlined a pre-renal transplant screening algorithm to incorporate VO2peak testing among a population of asymptomatic high-risk patients (with diabetes mellitus and/or >50 years of age). Only those with VO2peak <17 mL/kg per minute (equivalent to <5 metabolic equivalents) underwent further noninvasive cardiac screening tests. We conducted a retrospective study of the a priori dichotomization of the VO2peak <17 versus ≥17 mL/kg per minute to determine negative and positive predictive value of future cardiac events and all-cause mortality. We report a high (>90%) negative predictive value, indicating that VO2peak ≥17 mL/kg per minute is effective to rule out future cardiac events and all-cause mortality. However, lower VO2peak had low positive predictive value and should not be used as a reliable metric to predict future cardiac events and/or mortality. In addition, a simple mathematical calculation documented a cost savings of ≈$272 600 in the cardiac screening among our study cohort of 637 patients undergoing evaluation for kidney and/or pancreas transplant. CONCLUSIONS: We conclude that incorporating an objective measure of cardiorespiratory fitness with VO2peak is safe and allows for a cost savings in the cardiovascular screening protocol among higher-risk phenotype (with diabetes mellitus and >50 years of age) being evaluated for kidney transplant.

Progression of Interstitial Fibrosis during the First Year after Deceased Donor Kidney Transplantation among Patients with and without Delayed Graft Function.

BACKGROUND AND OBJECTIVES: Delayed graft function is a form of AKI resulting from ischemia-reperfusion injury. Our aim was to study the effect of delayed graft function on the progression of interstitial fibrosis after deceased donor kidney transplantation. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Our study is a retrospective study of all patients transplanted at our center between July of 2003 and September of 2014 using a kidney from a deceased donor. The primary outcome was the progression of interstitial fibrosis on serial protocol biopsies done during the first year post-transplant. We analyzed the distribution of the change in the Banff interstitial fibrosis (ci) score between the delayed graft function and nondelayed graft function groups for all of the paired biopsies done at time 0 and 12 months post-transplant (Δfibrosis). We also performed a linear mixed model analyzing the difference in the slopes for the progression of mean Banff ci score for all of the biopsies done at time 0 and 1, 4, and 12 months post-transplant. RESULTS: There were 343 (36.7%) in the delayed graft function group and 591 in the control group. The biopsy rates for the delayed graft function and nondelayed graft function groups at time 0 were 65.3% (n=224) and 67.0% (n=396), respectively, and at 12 months, they were 64.4% (n=221) and 68.4% (n=404), respectively. Paired biopsies were available for 155 in the delayed graft function group and 283 in the control group. In a risk-adjusted model, Banff ci score >0 on the time 0 biopsy had a higher odds of delayed graft function (odds ratio, 1.70; 95% confidence interval, 1.03 to 2.82). The distribution of the Δfibrosis between 0 and 12 months was similar in delayed graft function and control groups (P=0.91). The slopes representing the progression of fibrosis were also similar between the groups (P=0.66). CONCLUSIONS: Donor-derived fibrosis may increase the odds of delayed graft function; however, delayed graft function does not seem to increase the progression of fibrosis during the first year after transplantation.

Calcific uraemic arteriolopathy.

A 37-year-old African-American woman with end-stage renal disease presumed to be secondary to diabetes mellitus type 2, on daily peritoneal dialysis, was admitted for a painful left lower extremity lesion. Examination revealed a large, dusky, tender region over the left lateral thigh. She was on warfarin for mechanical heart valves. Despite discontinuation of warfarin and placement on heparin, the lesion progressed to extend to the medial left thigh and medial and lateral right thigh. CT scan demonstrated arteriolar medial calcification and vascular calcification of the small subcutaneous vessels, without evidence of abscess or haematoma. The patient declined punch biopsy. Given the known risk factors of high calcium-phosphate and radiological findings, a diagnosis of calcific uraemic arteriolopathy was made. Phosphate-binder therapy was optimised. She was transitioned to daily haemodialysis, and sodium thiosulfate was initiated. Skin lesions demonstrated improvement at her 5 weeks posthospitalisation follow-up.