Exploring associations between anthropometric indices and graft function in patients receiving renal transplant.

BACKGROUND: The aim of the present study was to identify indicators of malnutrition, as obtained by anthropometric measurements, that might be potential predictors of transplant outcomes. METHODS: One hundred and three patients receiving a graft from a living or a deceased donor were included in this prospective study. Body mass index (BMI) based on pretransplant dry body weight, triceps skinfold, mid-arm muscle circumference and corrected mid-arm muscle area were measured. Post-transplant data on delayed graft function (DGF) and glomerular filtration rate (GFR) at discharge were collected until patient discharge. RESULTS: Delayed graft function developed in 36.9% of the patients. BMI was the only anthropometric variable associated with a higher likelihood of DGF (odds ratio = 1.25, 95% confidence interval = 1.07-1.47) after adjusting for age, gender, donor group, donor age and years of dialysis before transplantation. Obesity was associated with a higher frequency of DGF (83.3% versus 31.1%, P = 0.001) compared to normal weight. GFR at discharge was negatively associated with BMI [ß = -0.014 (0.005), P = 0.004], being overweight [ß = -0.151 (0.041), P < 0.001] and obesity [ß = -0.188 (0.053), P = 0.001], after adjusting for age, gender, donor group, donor age and years of dialysis, but was not associated with indices of muscle reserves. CONCLUSIONS: The likelihood of DGF was higher among obese patients, whereas GFR at discharge was negatively associated with being overweight and obesity.

Lupus nephritis and non-Hodgkin lymphoma simultaneously diagnosed in a patient on methimazole.

A 78 year old white male on methimazole due to Grave's thyroiditis presented with acute renal failure after a short term history of progressive shortness of breath, malaise, myalgias, arthralgias, and bilateral lower limb swelling. The abdomen was remarkable for splenomegaly and lower extremities for erythema nodosum. No peripheral lymphadenopathy was detected. Serum albumin was 1.7 g/dl and very high erythrocyte sedimentation rate. Urine sediment was very active with dysmorphic red blood cells and casts and significant proteinuria (6.6 grams/day). Serum complements were abnormally low and antinuclear and anti-DNA antibodies were positive. Renal histopathology revealed membranoproliferative glomerulonephritis, along with a full house pattern on IFF consistent with lupus nephritis. Bone marrow aspiration revealed a 40% infiltration by a lymphocyte population of small cells consistent with a B cell non-Hodgkin lymphoma. The patient was treated with methylprednisolone, cyclophosphamide and rituximab and acute dialysis. Over the following weeks the patient became dialysis independent and returned to his baseline GFR.

PCSK9 and inflammatory biomarkers in the early post kidney transplantation period.

OBJECTIVE:   Various biomarkers have been studied in the early post-kidney transplantation (post-KTx) period in order to identify potential therapeutic targets for improving long-term graft survival. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a biomarker that has recently gained interest in cardiovascular disease but its role still remains to be defined post-KTx. PATIENTS AND METHODS: We prospectively evaluated the levels of PCSK9, interleukin (IL)-6, WBC and C-reactive protein in seventy-three hemodialysis patients undergoing KTx, at 3 time-points; pre-transplantation (day 0) and at 1 and 6-months post-KTx. All data were also analyzed according to donor-type (living or deceased) and compared with hemodialysis patients on transplant waiting list. RESULTS: At Day 0 there was no difference in WBC, CRP, IL-6 and PCSK9 levels between patients scheduled for transplantation and those who remained on hemodialysis. In transplanted patients WBC, CRP and IL-6 levels were significantly reduced early post-KTx [logIL-6 Day 0: 0.68 (0.33, 0.85) vs. 1-month: 0.57 (0.37, 0.75) vs. 6-months: 0.50 (0.32, 0.69) pg/ml, p=0.01], while PCSK9 levels were significantly increased (Day 0: 199.8±63.0 vs. 1-month: 276.2±79.4 vs. 6-months: 245.9±62.5 ng/ml, p<0.001). In contrast, no change of WBC, CRP, IL-6 and PCSK9 levels was observed in hemodialysis patients on follow-up (p=NS for all). Between living-donor and deceased-donor recipients, analysis showed reduced CRP and increased PCSK9 levels in both groups (p<0.05 for all), while IL-6 levels were reduced in living-donor and increased in deceased-donor recipients 1-month post-KTx. PCSK9 levels were not correlated with renal function, delayed graft function, rejection episodes or inflammatory biomarkers. CONCLUSIONS: PCSK9 levels were increased post-KTx independently from renal function and inflammatory biomarkers, in both living and deceased-donor recipients.

Evolution of Fabry disease in male patients: the Greek experience.

Fabry disease is a progressive metabolic disorder with a clinical course characterized by different phases and a variety of disease manifestations. The first symptoms generally appear in childhood or early adolescence and are followed by late life-threatening complications involving vascular, renal, cardiac, and cerebral systems. We report the clinical and biochemical characteristics of 16 male patients from 10 unrelated families who represent almost the entire cohort of known Fabry patients in Greece. Despite the presence of early symptoms in almost every patient (mean age at onset of symptoms 15.6 years), the diagnosis was delayed for a mean of about 18 years (mean age of diagnosis 36 years). Patients are currently monitored and the majority (15 out 16 patients) treated with Enzyme Replacement Therapy.

EULAR points to consider for conducting clinical trials in systemic lupus erythematosus: literature based evidence for the selection of endpoints.

OBJECTIVE: To assess available evidence on the use of end-points (outcome measures) in clinical trials in systemic lupus erythematosus (SLE), as a part of the development of evidence-based recommendations for points to consider in clinical trials in SLE. METHODS: The European League Against Rheumatism (EULAR) Task Force on SLE comprised 19 specialists, a clinical epidemiologist and a research fellow. Key questions addressing the evidence for clinical trial end-points in SLE were compiled using the Delphi technique. A systematic search of the PubMed and Cochrane Library databases was performed using McMaster/Hedges clinical query strategies and an array of relevant terms. Evidence was categorised based on sample size and type of design, and the categories of available evidence were identified for each recommendation. The strength of recommendation was assessed based on the category of available evidence and agreement on the statements was measured across the 19 specialists. RESULTS: Eight questions were generated regarding end-points for clinical trials. The evidence to support each proposition was evaluated. The literature review revealed that most outcome measures used in phase 2/3 trials in SLE have not been formally validated in clinical trials, although some indirect validation has been undertaken. CONCLUSION: This systematic literature review forms the evidence base considered in the development of the EULAR recommendations for end-points in clinical trials in SLE.

EULAR points to consider for conducting clinical trials in systemic lupus erythematosus.

OBJECTIVE: Systemic lupus erythematosus (SLE) is a complex multi-organ disease, characterised by relapses and remissions. DESIGN: ng a high-quality randomised controlled trial poses many challenges. We have developed evidenced-based recommendations for points to consider in conducting clinical trials in patients with SLE. METHODS: The EULAR Task Force on SLE comprised 19 specialists and a clinical epidemiologist. Initially, the evidence for clinical trial end-points in SLE was evaluated and this has been reported separately. A consensus approach was developed by the SLE Task Force in formulating recommendations for points to consider when conducting clinical trials in SLE. RESULTS: The literature review revealed that most outcome measures used in phase 2/3 trials in SLE have not actually been validated in clinical trials, although other forms of validation have been undertaken. The final recommendations for points to consider for conducting clinical trials in SLE address the following areas: study design, eligibility criteria, outcome measures including adverse events, concomitant therapies for SLE and its complications. CONCLUSIONS: Recommendations for points to consider when conducting clinical trials in SLE were developed using an evidence-based approach followed by expert consensus. The recommendations should be disseminated, implemented and then reviewed in detail and revised using an evidence-based approach in about 5 years, by which time there will be further evidence to consider from current clinical trials.

Mycophenolate mofetil as maintenance therapy in patients with vasculitis and renal involvement.

AIM: Cytotoxic drugs have reduced the mortality in patients with ANCA-associated vasculitis (AASV) but their use carries a substantial risk of toxicity. Efforts are made to switch from cytotoxic drugs to less toxic maintenance regimens. In this study we aimed to assess the efficacy of mycophenolate mofetil (MMF) as maintenance therapy in patients with AASV and renal involvement. METHODS: 22 patients with newly diagnosed AASV, microscopic polyangiitis (MPA) (n = 16), Wegener's granulomatosis (WG, n = 4), renal limited vasculitis (RLV, n = 1) and Churg-Strauss syndrome (CSS, n = 1) and renal involvement were followed for a median of 42 months (range 24 - 101). After 6 months of standard induction therapy, patients were switched to MMF monotherapy for 18 months. Renal parameters i.e. serum creatinine, proteinuria and urine sediment, BVAS scores and ANCA titers were assessed at baseline, after induction and after 18 months with MMF. RESULTS: After the end of induction, 3 of the 4 patients who were initially hemodialysis (HD) dependent, remained on HD and were withdrawn from further analysis. In the remaining 19 patients, the improvement in renal function (p < 0.001), hematuria (p = 0.011), proteinuria (p = 0.007) and BVAS scores (p < 0.001) after induction was sustained after 18 months maintenance with MMF and no patient relapsing during this period. Until the end of the follow up, 31.58% of patients relapsed, at a median of 21.5 months (range: 18 - 60). Side effects were transient and infrequent. CONCLUSION: In patients with AASV and renal involvement, MMF seems to be an effective and well tolerated option in sustaining short- and medium-term remission.

EULAR recommendations for the management of systemic lupus erythematosus. Report of a Task Force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics.

OBJECTIVE: Systemic lupus erythematosus (SLE) is a complex disease with variable presentations, course and prognosis. We sought to develop evidence-based recommendations addressing the major issues in the management of SLE. METHODS: The EULAR Task Force on SLE comprised 19 specialists and a clinical epidemiologist. Key questions for the management of SLE were compiled using the Delphi technique. A systematic search of PubMed and Cochrane Library Reports was performed using McMaster/Hedges clinical queries' strategies for questions related to the diagnosis, prognosis, monitoring and treatment of SLE. For neuropsychiatric, pregnancy and antiphospholipid syndrome questions, the search was conducted using an array of relevant terms. Evidence was categorised based on sample size and type of design, and the categories of available evidence were identified for each recommendation. The strength of recommendation was assessed based on the category of available evidence, and agreement on the statements was measured across the 19 specialists. RESULTS: Twelve questions were generated regarding the prognosis, diagnosis, monitoring and treatment of SLE, including neuropsychiatric SLE, pregnancy, the antiphospholipid syndrome and lupus nephritis. The evidence to support each proposition was evaluated and scored. After discussion and votes, the final recommendations were presented using brief statements. The average agreement among experts was 8.8 out of 10. CONCLUSION: Recommendations for the management of SLE were developed using an evidence-based approach followed by expert consensus with high level of agreement among the experts.

Urological complications: analysis and management of 1525 consecutive renal transplantations.

Urological complications after renal transplantation increase morbidity, delay graft function, and occasionally lead to graft and/or patient loss. The aim of this study was to analyze the causes of and therapeutic approaches to urological complications in renal transplantation as they related to patient outcomes. A series of 1525 consecutive renal transplantations were performed over a 24-year period. Renal grafts were obtained in 814 cases from living-related and in 711 from cadaveric donors. A Lich-Gregoire ureterovesical reimplantation technique with minimal bladder wall dissection was employed in all cases. Ureteral stents were routinely used in cadaveric transplants and exceptionally among living-related grafts. Urological complications were classified according to the mechanism and site of urinary tract involvement: graft ureteropelvic junction obstruction/stenosis (A), ureteral obstruction/stenosis (B), ureterovesical anastomosis obstruction/stenosis (C), urinary leakage (D), and other (E). Overall, we encountered 96 urological complications (6.3%). Group C complications occurred in 29 cases (30.2%), followed by 27 cases (28.1%) for group B patients, 25 cases (26.0%) for group D, 12 cases (12.5%) for group A, and 3 cases (3.1%) for group E patients. Surgical intervention was required in 49 (51.0%) of all urological complications. The others (n = 47, 49.0%) were treated either conservatively or by minimally invasive procedures. A rapid diagnosis of urological complications, assisted by early posttransplant DTPA scans, routine ultrasonography, and especially prompt treatment, resulted in compensation of renal graft dysfunction in the vast majority (n = 90, 93.8%) of cases. Surgical techniques of graft retrieval and reimplantation are of utmost importance to minimize the incidence of urological complications.

Angioplasty and stenting of arterial stenosis affecting renal transplant function.

PURPOSE: To evaluate the efficacy of percutaneous angioplasty and stenting in cases of artery stenosis of the transplanted kidney or proximal iliac artery stenosis causing transplant dysfunction and/or increase of the arterial blood pressure. MATERIALS AND METHODS: Between January 1999 and June 2007, we evaluated 24 patients who had undergone renal transplantation and subsequently were diagnosed with refractory hypertension and transplant dysfunction for signs of possible renal transplant artery stenosis. Color Doppler ultrasonography and magnetic resonance angiography preceded the intrarterial angiographic investigation, with false-negative results in 18.2% and 13.6% of patients, respectively. In 2 of the 24 patients, angiography did not reveal arterial stenosis affecting the transplanted kidney. Two patients had severe ipsilateral iliac artery stenosis and the remaining 20 had transplant artery stenosis. Successful angioplasty and stenting were performed in these 22 patients. RESULTS: The method was technically feasible in 100%. The procedure-related morbidity was 0%. During the follow-up period (range: 3 to 104 months), two patients died with normal transplant function, two suffered transplant failure, and the remaining 18 still have normal transplant function and easily controlled hypertension. CONCLUSION: Percutaneous angioplasty and stenting in cases of arterial stenosis affecting the renal transplant function are safe and effective procedures. Even more, the strong clinical suspicion must lead to angiographic investigation regardless of the results of other imaging approaches.

Colchicine in Renal Diseases: Present and Future.

Colchicine is a lipophilic alkaloid drug, which exhibits ant-inflammatory and anti-fibrotic properties. Cardinal mechanisms of action of colchicine are the disruption of the microtubule system and the inhibition of neutrophil adhesion and recruitment. Colchicine is indicated in the prevention and treatment of gouty arthritis and familial Mediterranean fever. In this review, we summarize current and potentially future pharmacologic activities of colchicine in various renal disease entities along with pharmacokinetic and pharmacodynamic properties. Additionally, we will refer to main interactions of colchicine with medications used in renal medicine, as well as dosing recommendations in patients with reduced glomerular filtration rate.

Glomerular Diseases and Renal Transplantation: Pathogenic Pathways and Evolution of Therapeutic Interventions.

Glomerular diseases and renal transplantation are the main fields of nephrology in which the immune system plays a prevalent role. Glomerular diseases have traditionally been attributed to auto-immune conditions, whereas allograft rejection has been considered an allo-immune response. However, common immunopathologic mechanisms that include Toll-like receptors, complement and B-cell activation, as well as genetic and infectious factors appear to be involved in the pathogenesis of both entities. Novel therapeutic regimens directed against specific targets of the immune system show promising results in glomerulopathies as well as in renal transplantation.

Syndrome of Inappropriate Antidiuretic Hormone Secretion Complicating Systemic Nocardiosis in a Renal Transplant Recipient: A Case Report.

BACKGROUND: Infection by Nocardia species is an uncommon cause of severe clinical syndromes, particularly in immunocompromised patients, and solid-organ transplantation is the most common underlying condition. The syndrome of inappropriate antidiuretic hormone secretion (SIADH) has been described thus far in lung and stem cell transplants with systemic nocardiosis. CASE REPORT: We report the first case of SIADH in a female elderly renal transplant recipient diagnosed with systemic nocardiosis 2 years after transplantation. The SIADH was managed appropriately, and her immunosuppressive regimen remained unchanged but was adjusted at a lower level. The systemic Nocardia infection was successfully treated with intravenous administration of trimethoprim-sulfamethoxazole and imipenem for 2 weeks followed by oral trimethoprim-sulfamethoxazole for a total of 12 months. CONCLUSIONS: The SIADH syndrome is a recognizable complication of Nocardia infection in renal transplant recipients. Prompt identification along with proper management and prolonged antimicrobial treatment are essential to improve patients' outcome.

Biopsy-related hemorrhage of renal allografts treated by percutaneous superselective segmental renal artery embolization.

INTRODUCTION: Biopsy-related vascular injuries in renal transplants are rare, but they can lead to dramatic clinical symptoms prompting immediate treatment. Transcatheter embolization is a minimally invasive technique used to treat some forms of arterial bleeding. This study evaluated the efficacy of this technique in iatrogenic biopsy-related vascular lesions in renal allografts. MATERIALS AND METHODS: Over the last eight years, six patients with severe renal hemorrhage were admitted to the angiography department of our hospital for evaluation and possible further treatment. All of them had a history of previous biopsy of a transplanted kidney. They all presented with clinical signs of hemodynamic instability. Angiographic investigation of the kidneys preceded further intervention in all cases. All underwent hyperselective embolization of the specific bleeding vessel with the use of microcoils and/or gelfoam particles. RESULTS: Successful embolization of the feeding artery could be performed in all patients. Superselective segmental renal artery embolization had a successful outcome concerning a steady renal function and a stable clinical course. No complications occurred. CONCLUSION: Transcatheter embolization is a safe and efficient endovascular technique to treat biopsy-related vascular injuries in renal transplants. Immediate clinical success and significant benefit in renal function can be obtained, and the longevity of the allograft after successful embolization mainly depends on the natural outcome.

Diabetic muscle infarction after kidney and pancreas transplantation: case report and literature review.

Diabetic muscle infarction (DMI) is a rare, long-term complication of poorly controlled diabetes (typically of type I). DMI was first described in 1965 and more than 100 cases have been reported thereafter in the English literature. Usually, there is a coexistence with concomitant nephropathy, neuropathy, and retinopathy. The etiology remains uncertain, but appears to be attributable to diabetic microangiopathy and hypercoagulability and is believed that hypoxia-reperfusion injury is involved. DMI presents with sudden onset of pain associated with a tender mass in the thigh in most instances. The diagnosis is based on magnetic resonance imaging, which is not specific but highly indicative. Treatment is conservative with relapses occurring in 50% of the patients, but not necessarily in the same muscle group. We describe a case of DMI that occurred 4 months after simultaneous kidney and pancreas transplantation in one patient with type I diabetes mellitus and end-stage renal disease.

Comparison between transcranial color Doppler ultrasonography and angiography in the confirmation of brain death.

OBJECTIVE: Cerebral blood flow tests have increasingly been advocated for the confirmation of brain death (BD). Angiography has been considered the gold standard in the diagnosis of BD but is invasive. We validated transcranial color Doppler ultrasonography (TCD) to confirm BD by comparing it to angiography. PATIENTS AND METHODS: Forty patients experienced the clinical diagnosis of brain death due to head injury in 19 cases (47.5%), cerebral hemorrhage in 11 (27.5%), subarachnoid hemorrhage in 7 (17.5%), and cerebral infarction in 3 (7.5%). Blood pressure, heart rate, SPO2, and PCO2 were monitored throughout the study. Patients were excluded if episodes of hypoxia, arrhythmia, and hypotension occurred during examinations, or if the TCD was not technically feasible. RESULTS: Both angiography and TCD confirmed BD in all patients. The agreement between the above methods to confirm BD was 100%. Angiography showed the absence of filling of intracranial arteries, while TCD revealed: (1) brief systolic forward flow or systolic spikes and diastolic reversed flow (50%); (2) brief systolic forward flow or systolic spikes and no diastolic flow (25%); (3) no demonstrable flow in a patient in whom flow had been clearly documented on a previous TCD examination (12.5%). Five patients required repeated TCD examinations, because of initial detection of a diastolic to-and-fro flow pattern. BD was confirmed by TCD in the above patients after 30 hours of clinical BD. CONCLUSION: TCD was a sensitive tool to diagnose BD, affording a reliable alternative examination to standard angiography.

Transorbital sonographic monitoring of optic nerve diameter in patients with severe brain injury.

OBJECTIVE: We investigated whether alterations in the optic nerve diameter (OND) correlated with brain computed tomography (CT) imaging results among patients with brain injury and whether monitoring of OND could predict brain death. PATIENTS AND METHODS: We enrolled 54 patients with brain injury (Glasgow Coma Scale < 8) and 53 controls. OND measurements were performed 3 mm posterior to the papillae by means of transorbital sonography. The severity of the injury was classified according to a semiquantitative CT neuroimaging scale (1 to 4). All patients underwent 3 repeated evaluations of OND combined with synchronous CT scans. RESULTS: Twenty-two patients progressed to brain death, while 32 patients showed gradual clinical improvement. Upon admission, the patients showed significantly increased OND (4.84 +/- 1.2 mm) compared with the controls (3.49 +/- 1.1 mm; P < .001). The median intraobserver variation of OND was 0.2 mm (95% confidence intervals [CI]: 0.1-0.7). The median interobserver variation of OND was 0.3 mm (95% CI: 0.1-0.9). Alterations in the OND were significantly correlated with the neuroimaging scale on 3 repeated evaluations: r = .65, r = .70, and r = .73 (all P < .001). An OND greater than 5.9 mm (specificity = 65% and sensitivity = 74%; P < .01) and a 2.5 mm increased OND between repeated measurements (specificity = 70% and sensitivity = 81%; P < .01) were associated with a poor prognosis. CONCLUSIONS: Alterations in OND strongly correlated with neuroimaging results among patients with brain injury. However, monitoring of OND exhibited a low predictive value for brain death.

A Heartbreaking Renal Transplantation: Is Norepinephrine the Culprit to Blame?

INTRODUCTION: Takotsubo cardiomyopathy (TCM), also known as "broken heart syndrome," "apical ballooning syndrome," and "stress-induced cardiomyopathy," was first described in Japanese patients in 1990 by Sato et al. TCM is an increasingly recognized syndrome characterized by transient and reversible systolic dysfunction of the apical and middle segments of the left ventricle. This syndrome resembles acute myocardial infarction in the absence of evident coronary artery occlusion. Herein, we present a case of a 51-year-old male who underwent his second deceased-donor renal transplantation for end-stage-renal-disease due to a work-related accident. Perioperatively, initiation of continuous infusion of noradrenaline was decided to achieve adequate graft perfusion due to persistently low blood pressure. On the second postoperative day, the patient experienced tachycardia and atypical angina-like chest pain. Electrocardiogram (ECG) showed signs of myocardial infarction and elevated troponin levels were observed. Urgent coronary angiography was normal and transthoracic echocardiography (TEE) was indicative for Takotsubo cardiomyopathy. DISCUSSION: Although, the precise pathophysiology of Takotsubo cardiomyopathy is still unknown, it seems that it is associated with excessive sympathetic stimulation, microvascular dysfunction, coronary artery vasospasm, and abnormal myocardial tissue metabolism. The development of patient's symptoms after the initiation of norepinephrine along with their immediate resolution after the discontinuation of the drug might suggest a causal relationship. This is the first time that TCM after renal transplantation is thought to be linked with the administration of exogenous catecholamines.

A comparative randomised study of valacyclovir vs. oral ganciclovir for cytomegalovirus prophylaxis in renal transplant recipients.

An open, prospective, randomised study was conducted to compare the safety and efficacy of valacyclovir vs. oral ganciclovir for cytomegalovirus (CMV) prophylaxis in renal transplant recipients. Eighty-three renal transplant recipients were assigned randomly to receive valacyclovir (n=43) or oral ganciclovir (n=40) for the first 3 months after transplantation. Both groups were similar in terms of demographics, primary renal disease, graft source, HLA matching, immunosuppressive therapy and donor-recipient CMV antibody status. CMV infection was diagnosed by detection of virus DNA in plasma with the Amplicor CMV Test. CMV disease was observed in only one patient belonging to the ganciclovir group, who developed enterocolitis 6 months post-transplantation. No difference was observed between the two treatment groups with respect to detection of CMV DNA, virus infections other than CMV, acute rejection episodes, and serum creatinine levels at 3 and 6 months following transplantation. An increased number of bacterial infections was noted in the ganciclovir group (p 0.003). No adverse reactions with either treatment were reported. The estimated cost of valacyclovir treatment was 20% higher than that of ganciclovir treatment. Overall, both valacyclovir and oral ganciclovir were found to be effective and safe for CMV prophylaxis in renal transplant recipients. Decisions regarding prophylactic regimens should include additional criteria, such as cost or possible development of resistance.