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Vitamin D is of paramount importance to skeletal development, integrity and health. Vitamin D homeostatis is typically deranged in a number of chronic conditions, of which chronic kidney disease is one of the most important. The use of vitamin D based therapy to target secondary hyperparathyroidism is now several decades old, and there is a large body of clinical practice, experience, guidelines and research to underpin this. However, there are many unknowns, of significant clinical relevance. Amongst which is what "species" of vitamin D we should be using, in what patient, and, under what conditions. Sadly, there has been a real dearth of randomised controlled trials, and trials with outputs of clinical relevance, which means our clinical practice has not developed and refined adequately ove the last 4 decades. This article will discuss the vexed but critical questions of which vitamin D therapies might suit which kidney patients, and will high-light the many important clinical questions which urgently require answering.

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Patients with cardiac morbidity are known to have increased risk of developing renal disease, and vice versa. Cardiorenal syndrome is a general term describing concomitant cardiac and renal dysfunction, and recently there has been renewed interest in the role of uric acid (UA) in its pathophysiology and management. There is evidence to suggest that UA-lowering drugs, such as the xanthine oxidase (XO) inhibitors allopurinol and Febuxostat, may not only retard deteriorating renal function in the context of chronic kidney disease (CKD) but also confer protective cardiovascular effects. As these diseases represent considerable health burdens, this evidence merits evaluation to determine whether or not hyperuricaemia is a cardiorenal risk factor that necessitates intervention and if existing pharmacological agents are sufficiently efficacious.

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BACKGROUND: Vascular calcification (VC) is common and is both a marker and a cause of increased cardiovascular morbidity and mortality, especially so in chronic kidney disease (CKD) patients. Renal transplantation is the cornerstone of the successful long-term management of CKD, and in order to satisfy transplantation needs, more use is made now of living kidney donors (LKD). Prior to selection for transplantation, much screening of potential LKD takes place, including for cardiovascular issues. It is not known; however, how much these potentially healthy LKD may be prone to clinically silent VC. METHODS: We identified 103 living kidney donors from 2011 renal transplant records. Abdominal aortic calcification (AAC) was assessed using existing abdominal CT imaging using multi-channel CT aortograms (used primarily to assess renal vascular anatomy). Using these CT scans, manual calcium scoring was undertaken to calculate total aortic calcium load (AAC severity score). The prevalence, severity and associations of AAC between calcified and non-calcified donors were then compared. RESULTS: A total of 103 donors were identified from records. Ninety three of these had detailed clinical records to complement their CT scans. Fifty of ninety-three donors were male, and the mean age was 45.9 ± 1.8 years. Mean MDRD eGFR was 88.73 ± 2.97 ml/min/1.73 m(2). 7.14 ± 3.07 % of the aorta in these donors was calcified with a mean AAC severity score of 0.98 ± 0.56. In kidney donors >50 years of age, there was significantly more AAC than in those <50: 2.47 ± 1.56 versus 0.31 ± 0.29, p < 0.001. There was no relationship between the presence or severity of aortic VC and donor GFR, systolic blood pressure, pulse pressure, calcium-phosphate product or smoking. CONCLUSIONS: AAC prevalence, patterns and severity in this important donor population have not previously been described in the literature. There was relatively little VC in what would be regarded as a "healthy" donor population. VC was more common with age, but the other possible risk factors for the presence or severity of VC did not impact on overall AAC scores. VC did not influence vascular stiffness as represented by pulse pressure. Following the evolution of AAC over time in those who have donated a kidney, and lost some global renal function as a consequence, would be of considerable interest.

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Vascular calcification is a major challenge to the long-term health of many patients with chronic kidney disease, and patients receiving peritoneal dialysis therapy are no exception to this. The mechanisms behind vascular calcification are complex and diverse. There are several different imaging techniques that can be used to interrogate the vasculature in these patients, and the relative merits of these as research and screening tools we discuss. There are some recent epidemiological studies which throw fresh light on the implications of the development or progression of vascular calcification. Finally, an animal model experiment is reported which one day may open up the possibility of a successful therapeutic intervention.

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We recently identified an erythrocyte nucleotide accumulating in end-stage renal disease as 4-pyridone-3-carboxamide ribonucleotide triphosphate (4PYTP), a nucleotide never described previously. Plasma tryptophan concentration has been previously reported to be reduced in patients in chronic renal failure that is in turn associated with elevated precursors of tryptophan metabolism, including L -kynurenine and quinolinic acid, both of which have been implicated in the neurotoxic manifestations of chronic renal failure. Here we compare mean erythrocyte 4PYTP, and plasma tryptophan concentrations, in controls and four patient groups with renal impairment (10 per group) and confirmed a reduction in plasma tryptophan in patients on dialysis that corrected with renal transplantation. We found: An inverse correlation between plasma tryptophan and red cell 4PYTP concentrations (R(2)=0.44, P<0.001) when all patients were grouped together. Restoration of both tryptophan and 4PYTP concentrations to control values was only achieved following renal transplantation. 4PYTP was absent from erythrocytes in Molybdenum cofactor (MoCF) deficiency implicating aldehyde oxidase/dehydrogenase, a Molybdenum requiring enzyme. High 4PYTP erythrocyte concentrations in adenine or hypoxanthine-phosphoribosyltransferase deficient patients in severe uremia (113 microM and 103 microM), confirmed the lack of involvement of either enzyme in 4PYTP formation. We propose that 4PYTP is formed by a novel route involving the oxidation of the intermediates of NAD turnover from quinolinic acid by aldehyde oxidase.

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Two organ recipients developed serologic evidence of syphilis infection after renal transplantation from a common deceased donor with a history of treated syphilis. Testing of donor serum for syphilis, which occurred after transplantation, gave results interpreted as consistent with past infection. However, subsequent serologic results in the recipients suggested transmission of infection at transplantation due to active infection of the donor. This may be explained by recent donor re-infection in view of the current syphilis epidemic in the United Kingdom. An initial error in the treatment of recipients further served to highlight unfamiliarity in managing this resurgent infection in the context of organ transplantation.

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In renal transplantation the calcineurin inhibitors (CNIs) have played a crucial role in the reduction in acute rejection rates. Unfortunately this has not been matched by an improvement in long-term graft survival rate. The development of chronic allograft nephropathy (CAN) is the second most common cause of graft loss, after death from cardiovascular causes. CAN has a multifactorial aetiology that includes immunological and nonimmunological factors relating to both donor and recipient. The use of CNIs has been strongly implicated as a risk factor for the development of CAN. With the ongoing development of new immunosuppressant agents the possibility of avoiding the CNIs now exists. Many studies have been designed to investigate strategies to minimise or avoid CNI exposure and to prolong graft survival. To achieve CNI withdrawal whilst avoiding rejection, additional immunosuppressants need to be substituted into the drug regimen. Long-term side effects of the immunosuppressant used need to be taken into account when drug changes are being considered. In light of current evidence, CNI reduction with optimal use of mycophenolate mofetil appears to be the most effective strategy in managing the patient with CAN.

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The case of a man with progressive breathlessness and pulmonary infiltration caused by AL amyloidosis associated with multiple myeloma is presented. There was a marked peripheral eosinophilia, which has not previously been described with amyloidosis.

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We have investigated an unusual nucleotide that accumulates, with precursors, in the erythrocytes of patients in uraemia. This nucleotide is related chemically to the NAD breakdown product, N1-methyl-2-pyridone-5-carboxamide (Me2Py), found in high concentrations in the plasma of uraemic patients. Both Me2Py and the nucleotide accumulate to high concentrations in the blood during uraemia: our investigations of samples from renal out-patients have provided information on a plausible link between the two compounds.

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We show that GTP concentrations rise in the erythrocytes of renal transplant recipients receiving the immunosuppressant MMF, and demonstrate that this effect is not caused by poor renal function after engraftment. We propose a model that is consistent with our observations.

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Cytomegalovirus (CMV) is usually a complication of renal/solid organ or bone marrow transplantation. We describe three cases of severe CMV in the context of vasculitis immunosuppression.

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Rifampicin re-administration may cause immunologically mediated acute tubulo-interstitial injury. Retrospectively, 170 consecutive cases with acute renal failure (ARF) following re-treatment with rifampicin (71% males, 29% females, age 21 to 68 years) were analysed, which accounted for 12% of all ARF patients treated by two large dialysis referral centres in Romania, Timisoara and Iasi, between 1974-2001 and 1988-2001, respectively. The most frequent clinical features of rifampicin-induced ARF were: Anuria, gastro-intestinal (abdominal pain, nausea, vomiting and diarrhoea) and "flu-like" symptoms. Urine analysis revealed sterile leucocyturia in 54%, proteinuria in 31%, haematuria in 26% and haemoglobinuria in 7% of cases. Haemolytic anaemia was frequent, found in 66% of the patients; half of these had Hct values of < 30%, thrombocytopenia and also more severe renal damage (a longer anuric phase and a slower recovery of the renal function), thus suggesting a severe multi-target autoimmune aggression. The association of hepatic injury--not explained by prior hepatic disease, B or C hepatitis virus infection or history of alcohol abuse--was encountered in 17% of the cases, without a significant influence on the renal and the general outcome. The outcome of rifampicin-induced ARF is generally favourable, with complete recovery of the renal function within 30 days in 52% of the cases and within 90 days in 92% of the cases. The mortality rate was 3.5%, compared to 21% for the overall ARF population treated during the same period (p < 0.05).

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Endogenous Aspergillus endophthalmitis (AE) is a rare complication of invasive aspergillosis (IA) in transplant patients. In this report, we describe two patients with polycystic kidney disease, who developed AE with cerebral involvement after renal transplantation. Both patients received intense immunosuppression with methyl prednisolone and mycophenolate mofitil (MMF) because of persistent rejection, which rendered them diabetic and vulnerable to opportunistic infections. Endophthalmitis developed within six months of transplantation and was confirmed by microscopy and culture of the vitreous fluid. Patients were treated with combinations of different anti-fungal agents including liposomal amphotericin B, 5-flucytosine, itraconazole, voriconazole and terbinafine. In an electronic MEDLINE review, we found eight further cases of AE in renal transplant patients between 1959 and September 2002. Based on this review, we identified possible risk factors including CMV infection, diabetes mellitus and treatment for rejection with agents such as methyl prednisolone and MMF. In 70% of cases the histology, microscopy or culture of vitreous fluid confirmed the diagnosis. The outcome of AE in renal transplant patients was poor with 70-100% mortality. The review of reported cases and current practice guidelines suggests that vitrectomy and intravitreal amphoterecin B is the treatment of choice. In addition, new antifungal agents with good CSF and ocular penetration such as voriconalzole should be considered for the treatment of invasive cerebral/ocular aspergillosis.

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A man born in 1944 presented with an episode of macroscopic haematuria during a urinary tract infection in 1988. He was unusually tall at 2 metres. An intravenous pyelogram and an abdominal ultrasound disclosed the presence of bilaterally enlarged polycystic kidneys and a polycystic liver. There was a family history of renal disease. Plasma creatinine (180 micro mol/l) and blood pressure (150/100 mm Hg) were both raised. Despite good blood pressure control his renal function declined progressively and he started renal dialysis treatment in 1995. He received a renal allograft in 1996. In 1994 he had noticed a painful swelling behind his left knee. Computed tomography with contrast showed a large popliteal aneurysm. This was replaced with a vein graft. The right popliteal artery showed milder changes, and this was repaired in 1999. Popliteal aneurysms develop most often in older vasculopaths with multiple risk factors; connective tissue disorders have rarely been associated with their presence in younger patients. Polycystic kidney disease has been associated with several aneurysms, most notably cerebral, but not popliteal. The patient's marfanoid habitus also may have played a part. This case emphasises the mixed aetiology of popliteal aneurysms.

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Cushing's syndrome is characterised by circulating steroid excess; the mainstay of treatment of systemic sarcoidosis is steroid therapy. We describe a case of sarcoidosis emerging after treatment for Cushing's syndrome.

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Renal stones rarely complicate renal transplants. Their causation is diverse. We describe 2 patients with significant staghorn calculi caused by metabolic factors.

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Posterior Leukoencephalopathy Syndrome (PLES) is a rare but serious neurological condition with many aetiologies. In the era of organ transplantation there have been sporadic reports of calcineurin-inhibitor associated PLES. We describe a case, with subsequent uneventful retransplantation using sirolimus.

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