New onset diabetes after transplantation: Not another acronym!

New onset diabetes after transplantation is the onset of diabetes in previously non-diabetic individuals extending beyond the first month post-transplantation.

Renal artery stent revascularization with embolic protection in patients with ischemic nephropathy.

A prospective analysis of renal artery stent revascularization with distal embolic protection in a high-risk patient population with ischemic nephropathy is presented. A total of 63 patients (median age 70.2 years, range 54-86 years) had significant atherosclerotic stenosis of 83 renal arteries documented on pre-procedural imaging. All patients had baseline chronic renal insufficiency with a documented deterioration in renal function in the 6 months before revascularization. The endovascular technique used in all patients involved primary passage of an embolic filter into the distal main renal artery followed by primary stent deployment with a balloon expandable stainless steel stent. The filter baskets were recaptured and contents submitted for pathological analysis. At 6 months post-intervention, 97% of patients demonstrated stabilization or improvement in renal function. Only 3% of patients had an inexorable decline in renal function, unchanged by the intervention. After a mean follow up of 16.0 months (6-27), 94% of patients demonstrated stabilization or improvement in renal function. One patient suffered an acute post-procedural deterioration in renal function. In total, 60% of the filter baskets contained embolic material. This study confirms the technical feasibility of renal artery stent deployment with adjuvant embolic protection. The excellent results for renal preservation at 6 months post-intervention also suggest that a distal embolic protection device may improve the impact of percutaneous renal revascularization on progressive deterioration in renal function. The postulated mechanism is through the prevention of atheromatous embolization and the embolic yield from the distal filters supports this hypothesis. Patients most likely to receive the greatest benefit are those with mild baseline chronic renal insufficiency and a recent decline in renal function.

Cardiac assessment for renal transplantation.

Cardiac death is common in patients with end-stage renal failure. Screening for coronary artery disease prior to renal transplantation is advisable in high-risk patients. The optimal screening test has not been defined; however, myocardial perfusion studies are more sensitive than exercise electrocardiography and are less invasive than coronary angiography, which remains the gold standard. The management of coronary artery disease prior to transplantation is contentious. Revascularization of coronary artery stenoses is associated with high mortality and morbidity in the renal failure population, and there is little data to indicate that most patients with asymptomatic coronary lesions will benefit from prophylactic coronary intervention. In addition, beta-blockers and aspirin are under-utilized in the renal population. This paper reviews the literature and proposes algorithms for the cardiac assessment and management of patients prior to renal transplantation.

Time course of upregulation of fibrogenic growth factors and cellular infiltration in a rodent model of chronic renal allograft rejection.

BACKGROUND: Chronic Rejection (CR) is the leading cause of renal allograft dysfunction. Upregulation of growth factors has been shown in CR but the time point at which this occurs in not known. The aim of this study was to examine the time course of upregulation of growth factors and correlate this with the macrophage and myofibroblast interstitial infiltrate. METHODS: Using a rat model of CR (F344 kidney donor to Lewis recipient), infiltration by ED1 + macrophages and proliferation of alpha-smooth muscle actin (alpha-SMA) and desmin-expressing cells was examined using immunohistochemistry. In addition, expression of mRNA for interferon-gamma (IFN-gamma), transforming growth factor-beta (TGF-beta), basic-fibroblast growth factor (b-FGF) and vascular endothelial growth factor (VEGF) was studied using a semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) technique. Native Lewis rat kidney and Lewis-Lewis isografts were used as controls. RESULTS: Immunohistochemical staining of ED1 + cells showed a marked increase in the macrophage infiltrate of allografts compared to isografts at all time periods (P = 0.0002) peaking at weeks 8-12 after transplantation. Expression of alpha-SMA was also increased in allografts (P = 0.002). RT-PCR analysis showed that mRNA for TGF-beta was maximally upregulated in allografts in comparison to isografts at week 8 after engraftment (P = 0.05) and declined thereafter, although remained at elevated levels compared to controls. IFN-gamma and b-FGF gene expression was increased in allografts late in the post-transplantation period. CONCLUSION: Early infiltration of macrophages and production of TGF-beta1 was followed by later upregulation of fibrogenic growth factors and myofibroblasts associated with interstitial fibrosis and organ dysfunction.

Tacrolimus for the treatment of gout in renal transplantation: two case reports and review of the literature.

Episodes of gout are common in the setting of renal transplantation. Hyperuricemia and gout have been associated with the use of the calcineurin inhibitor, cyclosporine. We report two cases of severe polyarticular gout resistant to conventional therapy in renal transplant recipients that resolved after switching from cyclosporine to tacrolimus-based immunosuppression. There was no alteration in renal function, and trough concentrations of both cyclosporine and tacrolimus were within the recommended range. Resolution of gout occurred within a month of discontinuation of cyclosporine and commencement of tacrolimus. Use of tacrolimus may be beneficial in the renal transplant recipient with refractory gout.

Early up-regulation of macrophages and myofibroblasts: a new marker for development of chronic renal allograft rejection.

BACKGROUND: Increased numbers of macrophages and myofibroblasts are observed to occur in chronic renal allograft rejection (CR). The aim of this study was to examine the expression of cellular markers for the macrophage and myofibroblast in early renal transplant biopsy specimens and correlate these findings with allograft outcome. METHODS: The first postengraftment biopsy specimens from 53 patients who underwent renal transplantation between January 1993 and December 1995 were studied using immunohistochemistry with antibodies to alpha-smooth muscle actin, which identifies myofibroblasts and CD68, a marker for monocytes and macrophages. Patients were followed until December 1998 (mean follow-up 4.7+/-1.2 years). RESULTS: Nine patients had progressed to CR by the time of the study, whereas 44 patients continued to have stable renal function. A marked increase in both macrophages (P=0.02) and myofibroblasts (P=0.04) was noted in the first biopsy specimen obtained after engraftment in the patients who developed CR compared with those with stable allograft function. There was a positive correlation between alpha-smooth muscle actin and collagen expression (P=0.0001). CONCLUSION: Significant increases in macrophages and myofibroblasts occur in the first renal biopsy specimen in those patients who later develop CR.

A deficiency of placental IL-10 in preeclampsia.

Accommodation of the fetoplacental unit in human pregnancy requires maternal immune tolerance to this "semiallograft". Local antiplacental immunity is modified by synthesis of uncommon histocompatibility Ags (e.g., HLA-G), growth factors, and cytokines by the placenta. Placental interleukins have been identified in reproductive tissues, but their roles in adaptive maternal immunity and determining term pregnancy outcomes have not been fully clarified. This study examined the distribution of IL-10 and TNF-alpha staining in term placentas. Women with proteinuric hypertension (PE, n = 10) were compared with an age-matched group with normal pregnancy (NP, n = 14) and gestational hypertension (GH, n = 6). Using immunohistochemistry of parrafin-fixed tissues, trophoblast cells were identified by cytokeratin 7 and cytokeratin 18 staining. The cytokine binding of villous trophoblast cells was scored depending on the extent of circumferential cytoplasm staining (<25%; intermediate or >75%). The cytokine positive decidual cells were scored as a percentage of total extravillous trophoblast cells. There was a reduction in villous IL-10 immunostaining compared with normal term placenta (PE, 10.2 +/- 1.1, mean +/- SEM; NP, 14.07 +/- 1.16 Mann-Whitney U test; p = 0.02). In these patients, there was an increase in TNF-alpha immunostaining. Sparse endovascular extravillous trophoblast cells demonstrated nuclear IL-10 staining in 30% of patients with preeclampsia. Serum IL-10 was diminished in women with preeclampsia compared with normal pregnancy. In conclusion, villous trophoblast demonstrated diminished immunostaining of IL-10 in preeclampsia. This abnormality may be associated with heightened maternal antifetal immunity and therefore inadequate placental development in preeclampsia.

Vascular endothelial growth factor expression in human chronic renal allograft rejection.

BACKGROUND: Chronic renal allograft rejection is characterized by interstitial fibrosis and vasculopathy. Vascular endothelial growth factor (VEGF) is an endothelial mitogen with increased expression in inflammation and vasculopathy. METHODS: Renal tissue from 17 patients with chronic rejection was examined for VEGF protein and the presence of CD 68-positive macrophages, and compared to biopsies from patients with temporary allograft dysfunction, acute rejection, and native kidneys with thin membrane disease. RESULTS: In the chronic rejection group, there was markedly increased expression of VEGF protein in the interstitium (P<0.0001). In serial sections, VEGF colocalized with the expression of CD 68-positive macrophages. Significantly more macrophages were in the tubulointerstitium in tissue with chronic rejection than in those with temporary allograft dysfunction (P<0.005). Additionally, VEGF protein expression in the glomeruli and the vascular compartment of patients with chronic rejection was increased. CONCLUSION: The up-regulation of VEGF in chronic renal allograft rejection may be important in inflammation and development of fibrosis.

Acute bone pain following renal transplantation: differentiation between benign bone edema and avascular necrosis.

Two patients are reported who presented within the first 3 months posttransplantation with acute bone pain where serial magnetic resonance imaging (MRI) allowed differentiation between bone edema, which resolved spontaneously, and avascular necrosis (AVN) requiring core decompression. Case 1 had ill-defined images consistent with bone edema that resolved, whereas case 2 developed well-demarcated lesions in the femoral condyles and tibial epiphyses which were confirmed as AVN at surgery. Alternative explanations for bone edema were not evident. We would suggest that in any transplant recipient who develops acute bone pain, MRI is the initial diagnostic modality of choice. Evidence of development of well-demarcated lesions on serial MR scans indicate early AVN. However, on current evidence it is difficult to predict which lesions will progress and until greater experience becomes available, we would recommend intraosseous plethysmography and venography so that incipient or early AVN can be treated by core decompression of the affected bone.

Necrotising fasciitis: a single centre's experience.

AIMS: Necrotising fasciitis is a rare but serious soft tissue infection with high morbidity and mortality. We wished to review our 5 year experience with this condition 1989-94. In addition, in light of recent interest in the association between necrotising fasciitis and nonsteroidal antiinflammatory drugs, we wished to determine the incidence of NSAID use in our necrotising fasciitis patients. METHODS: A review of all Dunedin Hospital cases of necrotising fasciitis between January 1989-June 1994 was undertaken. Subsequently all specialists involved in treating the patients audited the notes, particularly regarding clinical presentation, complications, treatment, outcome and concomitant use of NSAIDs was also recorded. RESULTS: There have been seven patients (4 males) with a mortality rate of 43%. Survival was associated with early diagnosis, rapid and intensive medical and surgical intervention, and possibly the early use of haemofiltration. Five of the seven patients had ingested nonsteroidal antiinflammatory drugs (NSAID) prior to their presentation which may have potentiated the severity of the endotoxic shock. CONCLUSION: Necrotising fasciitis remains a potentially lethal disease but early management and aggressive treatment improves outcome. A high index of suspicion, avoidance of NSAIDs, and aggressive multidisciplinary team management of these patients offers the best chance of survival in necrotising fasciitis.

Prolonged bleeding time during ciprofloxacin therapy.

Ciprofloxacin is a broad spectum quinolone antibiotic. Side effects reported include nausea and other gastrointestinal symptoms; skin and musculoskeletal side effects may also occur. No bleeding abnormalities or alteration in coagulation have been documented. We report a case where ciprofloxacin appeared to contribute to an idiosyncratic prolongation of bleeding time although a rechallenge 8 months later did not reproduce the effect. Moreover, subsequent investigation of the influence of ciprofloxacin on bleeding parameters in 10 healthy volunteers demonstrated no alterations in bleeding parameters.

Acute bilateral renal artery occlusion: successful revascularization with streptokinase.

A case of acute oliguric renal failure due to bilateral renal artery occlusion is described. The renal function was restored to normal 36 h after the embolic event by revascularization with streptokinase.

Acute renal failure due to acute rhabdomyolysis precipitated by MAST trousers and diflunisal.

This report describes a patient who developed acute rhabdomyolysis and acute renal failure following the application of MAST trousers associated with an overdose of diflunisal. This association has not previously been reported.