Renal Histopathological Lesions After Lung Transplantation in Patients with Cystic Fibrosis

Enteric hyperoxalosis is a recognized complication of bariatric surgery, with consequent oxalate nephropathy leading to chronic kidney disease and occasionally end-stage renal failure. In patients with prior gastrointestinal bypass surgery, renal allografts are also at risk of oxalate nephropathy. Further, transplant recipients may be exposed to additional causes of hyperoxalosis. We report two cases of renal allograft oxalate nephropathy in patients with remote histories of bariatric surgery. Conservative management led to improvement of graft function in one patient, while the other patient returned to dialysis. Interpretation of serologic, urine and biopsy studies is complicated by oxalate accumulation in chronic renal failure, and heightened excretion in the early posttransplant period. A high index of suspicion and careful clinicopathologic correlation on the part of transplant nephrologists and renal pathologists are required to recognize and treat allograft oxalate nephropathy. As the incidence of obesity and pretransplant bariatric surgery increases in the transplant population, allograft oxalate nephropathy is likely to be an increasing cause of allograft dysfunction.

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Enteric Oxalate Nephropathy in the Renal Allograft: An Underrecognized Complication of Bariatric Surgery

Troxell

Houghton

Hawkey³

et al. 2013

“…Renal failure in these patients has been found to be a major risk factor for patient survival, mainly after heart and lung transplantation (4,6,7,14,(20)(21)(22)(23). Calcineurin- (24)(25)(26)(27). We report on our experience with 105 renal biopsies performed in 101 patients grafted with nonrenal organs and tissues.…”

Section: Transplanted Kidneys Fail After Years For Various Poorly Defmentioning

confidence: 99%

“…TMA was commonly observed in patients receiving cyclosporine after nonrenal transplantation, namely after bone marrow (40), liver (41,42), bone marrow and heart (43), heart, lung, and heart plus lung transplantation (44). In more recent publications, TMA-like changes in kidney biopsy, without the clinical signs of hemolysis and thrombopenia, have become more common (24,25 (45). The activity of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS 13) in plasma usually is not generally reduced (46), and the etiology of this localized TMA is unknown, although it could be an early form of later more typical cyclosporine vasculopathy (43).…”

Section: However Even the High Number Of Biopsies In This Report Doementioning

confidence: 99%

Biopsy‐Diagnosed Renal Disease in Patients After Transplantation of Other Organs and Tissues

Schwarz¹,

Haller²,

Schmitt³

et al. 2010

Renal function deteriorates in about half of patients undergoing other transplants. We report the results of 105 renal biopsies from 101 nonrenal transplant recipients (bone marrow 14, liver 41, lung 30, heart 20). Biopsy indications were protracted acute renal failure (9%), creatinine increases (83%), heavy proteinuria (22%), or renal insufficiency before re-transplantation (9%). Histological findings other than nonspecific chronic changes, hypertension-related damage, and signs of chronic CNI toxicity included primary glomerular disease (17%), mostly after liver transplantation (21%) or after bone marrow transplantation (29%), and thrombotic microangiopathy (TMA) namely (10%). TMA had the most serious impact on the clinical course. Besides severe hypertension, one TMA patient died of cerebral hemorrhage, 5 had hemolyticuremic syndrome, and 6 rapidly developed end-stage renal failure. TMA patients had the shortest kidney survival post-biopsy and, together with patients with acute tubular injury, the shortest kidney and patient survival since transplantation. Nine TMA patients had received CNI, 3 of them concomitantly received an mTOR-inhibitor. CNI toxicity is implicated in most patients with renal failure after transplant of other organs and may play a role in the development of TMA, the most serious complication. However, decreased renal function should not be routinely ascribed to CNI.

“…Unfortunately, the relationship between whole blood tacrolimus trough concentrations and the AUC is highly variable, especially peri-operatively, making interpretation of the former very challenging (12,(16)(17)(18). Even when tacrolimus concentrations are in the therapeutic range, toxicity may occur because of high unbound tacrolimus plasma concentrations (61). The variables influencing the bound and unbound tacrolimus concentrations may considerably change during the early postoperative phase.…”

Section: Pharmacokinetics Of Tacrolimus Early After Heart and Lung Trmentioning

confidence: 99%

Pharmacokinetics and Toxicity of Tacrolimus Early After Heart and Lung Transplantation

Sikma

Maarseveen

Graaf

et al. 2015

149

110

Annually, about 8000 heart and lung transplantations are successfully performed worldwide. However, morbidity and mortality still pose a major concern. Renal failure in heart and lung transplant recipients is an essential adverse cause of morbidity and mortality, often originating in the early postoperative phase. At this time of clinical instability, the kidneys are exposed to numerous nephrotoxic stimuli. Among these, tacrolimus toxicity plays an important role, and its pharmacokinetics may be significantly altered in this critical phase by fluctuating drug absorption, changed protein metabolism, anemia and (multi‐) organ failure. Limited understanding of tacrolimus pharmacokinetics in these circumstances is hampering daily practice. Tacrolimus dose adjustments are generally based on whole blood trough levels, which widely vary early after transplantation. Moreover, whole blood trough levels are difficult to predict and are poorly related to the area under the concentration‐time curve. Even within the therapeutic range, toxicity may occur. These shortcomings of tacrolimus monitoring may not hold for the unbound tacrolimus plasma concentrations, which may better reflect tacrolimus toxicity. This review focuses on posttransplant tacrolimus pharmacokinetics, discusses relevant factors influencing the unbound tacrolimus concentrations and tacrolimus (nephro‐) toxicity in heart and lung transplantation patients.