Search

Graphical Abstract Potential mechanisms contributing to myocardial injury and subsequent elevations in cardiac troponins in patients with COVID-19.

BACKGROUND: This study provides a summary of the 2010 European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry Annual Report (available at www.era-edta-reg.org). METHODS: This report includes data on renal replacement therapy (RRT) using data from the national and regional renal registries in 29 countries in Europe and bordering the Mediterranean Sea. Individual patient data were received from 27 registries, whereas 18 registries contributed data in aggregated form. We present incidence and prevalence of RRT, transplant rates, survival probabilities and expected remaining lifetimes. The latter two are solely based on individual patient records. RESULTS: In 2010, the overall incidence rate of RRT for end-stage renal disease (ESRD) among all registries reporting to the ERA-EDTA Registry was 123 per million population (pmp) (n = 91 798). The highest incidence rate was reported by Turkey (252pmp) and the lowest reported by Montenegro (21 pmp). The overall prevalence of RRT for ESRD at 31 December 2010 among all registries reporting to the ERA-EDTA Registry was 741 pmp (n = 551 005). The prevalence varied from 124 pmp in Ukraine to 1580 pmp in Portugal. The overall number of renal transplantations performed in 2010 among all registries was 29.2 pmp (n = 21 740). The highest overall transplant rate was reported from Spain, Cantabria (73 pmp), whereas the highest transplant rate for living donor kidneys was reported from the Netherlands (28 pmp). For patients who started RRT between 2001 and 2005, the unadjusted 5-year patient survival on RRT was 46.2% [95% confidence interval (CI) 46.0-46.3], and on dialysis 38.6% (95% CI 38.5-38.8). The unadjusted 5-year patient survival after the first renal transplantation performed between 2001 and 2005 was 86.6% (95% CI 86.1-87.1) for deceased donor kidneys and 94.1% (95% CI 93.4-94.8) for living donor kidneys.

Fever in haemodialysis patients is usually attributed to infection, with less frequent causes including malignancy and autoimmune disorders [1]. Sometimes, fever persists despite empirical treatment, and investigations towards the above mentioned diagnoses fail to reveal the cause. Thus, rarer aetiologies need to be considered, which may appear rather unexpected, especially in patients under prolonged medical follow-up.

Background. Little is known about the status of renal replacement therapy (RRT) in the post-Soviet countries. We therefore investigated the epidemiology and treatment outcomes of RRT in Ukrainian patients and put the results into an international perspective. Methods. Data from the Ukrainian National Renal Registry for patients on RRT between 1 January 2010 and 31 December 2012 were selected. We calculated the incidence and prevalence of RRT per million population (pmp) and the 3-, 12- and 24-month patient survival using the Kaplan– Meier method and Cox regression. Results. There were 5985 prevalent patients on RRTon 31 December 2012 (131.2 pmp). Mean age was 46.5 ± 13.8 years, 56% men and 74% received haemodialysis (HD), while peritoneal dialysis and kidney transplantation both represented 13%. The most common cause of end-stage renal disease was glomerulonephritis (51%), while only 12% had diabetes. In 2012, 1129 patients started dialysis (incidence 24.8 pmp), with 80% on HD. Mean age was 48 ± 14 years, 58% men and 20% had diabetes. Three, 12- and 24-month patient survival on dialysis was 95.1%, 86.0% and 76.4%, respectively. The transplant rate in 2012 was 2.1 pmp. Conclusions. The incidence and prevalence of RRT and the transplantation rate in Ukraine are among the lowest in Europe, suggesting that the need for RRT is not being met. Strategies to reduce the RRT deficit include the development and improvement of transplantation and homebased dialysis programmes. Further evaluation of the quality of Ukrainian RRTcare is needed.

Cytomegalovirus (CMV) infection is an important cause of morbidity in renal transplant recipients, due to both direct and indirect effects of the virus on the graft and patient [1]. Ganciclovir (GCV) remains the most common first-line therapy, but its low oral bioavailability was identified as a risk factor for the emergence of resistant strains [1], and intravenous (IV) administration is inconvenient for use in prophylactic or pre-emptive therapy. Valganciclovir (VGCV) is a prodrug of GCV with a much higher oral bioavailability, which makes it very useful for prophylaxis and pre-emptive therapy, as well as for treatment in selected patients [2–4]. Although initially associated with a negligible risk of drug resistance [5], subsequent papers identified patients with GCV-resistant CMV infection after VGCV prophylaxis and treatment [6, 7]. Patients with drug-resistant CMV strains often have more tissue-invasive disease and unfavourable clinical outcomes [8, 9], but there is some heterogeneity, and reports of asymptomatic infection, particularly in non-lung transplant recipients, suggest that some mutations are less pathogenic than others [10]. The therapeutic approach is a challenge and must balance the severity of the infection against the risks of drug toxicity and reduction of immunosuppression. We report two cases of GCV-resistant CMV from our unit: the first is a case of invasive CMV disease in a low-risk renal transplant recipient while on therapy with VGCV, and the second is a high-risk patient who developed GCV-resistant CMV infection while on VGCV prophylaxis.

Bacteremia is a major concern in hemodialysis patients being evaluated for fever, and identifying a source of ongoing infection is often challenging. In the absence of an obvious catheter-related nidus, clinicians typically consider a wide range of entities including endocarditis, osteomyelitis, joint infections and epidural abscesses. Despite advanced CT, magnetic or radionuclide imaging techniques, however, the site of continuing or relapsing infection can remain occult. We believe that endovascular stents are an under-appreciated potential location for such infections. The use of these devices has become increasingly common and is of particular concern when deployed for access-associated venous stenoses in dialysis patients. With the widespread use of endovascular devices, and especially in circumstances when care is rendered at multiple facilities, the patients and their medical providers may be unaware that those devices are present. There is much human and animal model literature describing the use of arterial and venous stents made from bare metal or combined with polymeric materials [1]. Although they are subject to infection upon implantation, it appears that the risk decreases with the endothelialization that historically was thought to occur over approximately 4 weeks. The speed and ultimate coverage area of cell growth is, however, controversial [2]. There is evidence that stents can become infected more than a month post-insertion, perhaps when associated with incomplete endothelial growth, thrombi or local trauma (e.g. needle cannulation) [3]. We present here a patient with persistent bacteremia due to an infected vena cava stent, complicated by the presence of a vegetation. This case highlights the importance of detecting these devices when evaluating febrile hemodialysis patients and the challenges in determining the optimal surgical or medical plan of care.

Retinal detachment (RD) is a serious condition that may lead to permanent loss of vision. Most RDs result from a tear(s) in the retina, through which liquefied vitreous enters the sub-retinal space. Rarely, however, exudative retinal detachment (ERD) occurs due to an underlying ocular or systemic condition that produces excess sub-retinal fluid in the absence of tears and/or tractional pull [1]. The ERD may go unnoticed especially if the patient is severely ill and may not complain of symptoms like floaters, flashes of light and peripheral visual field defect. Severe visual deficit occurs once the macula is involved in advanced ERD. Hence, a high level of suspicion is mandatory to detect ERD in these renal and gastroenterological conditions. We report a series of three patients who had ERD secondary to underlying systemic disease and interestingly were diagnosed only after blurring of vision occurred as their presenting symptom.

Background This article provides a summary of the 2011 ERA–EDTA Registry Annual Report (available at www.era-edta-reg.org). Methods Data on renal replacement therapy (RRT) for end-stage renal disease (ESRD) from national and regional renal registries in 30 countries in Europe and bordering the Mediterranean Sea were used. From 27 registries, individual patient data were received, whereas 17 registries contributed data in aggregated form. We present the incidence and prevalence of RRT, and renal transplant rates in 2011. In addition, survival probabilities and expected remaining lifetimes were calculated for those registries providing individual patient data. Results The overall unadjusted incidence rate of RRT in 2011 among all registries reporting to the ERA–EDTA Registry was 117 per million population (pmp) (n = 71.631). Incidence rates varied from 24 pmp in Ukraine to 238 pmp in Turkey. The overall unadjusted prevalence of RRT for ESRD on 31 December 2011 was 692 pmp (n = 425 824). The highest prevalence was reported by Portugal (1662 pmp) and the lowest by Ukraine (131 pmp). Among all registries, a total of 22 814 renal transplantations were performed (37 pmp). The highest overall transplant rate was reported from Spain, Cantabria (81 pmp), whereas the highest rate of living donor transplants was reported from Turkey (39 pmp). For patients who started RRT between 2002 and 2006, the unadjusted 5-year patient survival on RRT was 46.8% [95% confidence interval (CI) 46.6–47.0], and on dialysis 39.3% (95% CI 39.2–39.4). The unadjusted 5-year patient survival after the first renal transplantation performed between 2002 and 2006 was 86.7% (95% CI 86.2–87.2) for kidneys from deceased donors and 94.3% (95% CI 93.6–95.0) for kidneys from living donors.

Therapeutic plasma exchange (TPE) is a well-established treatment modality for nephrology patients, using two conventional methods: membrane (mTPE) or centrifugal TPE (cTPE). Although the efficacy of both treatments has been described, there are few reports that compare these methodologies. Here we describe three nephrology patients who were treated with both mTPE and cTPE. The mTPE method, but not the cTPE method, was associated with persistent difficulty anticoagulating the extracorporeal circuit in all three patients. In mTPE procedures, the doses of heparin bolus and infusion rate were important determinants of whether the circuit clotted. With a heparin bolus at or below 2000 IU, clotting occurred in 67% of treatments, dropping to 25% with a bolus of >2000 IU. Likewise, a heparin infusion rate during the procedure was indicative of clotting. With a maintenance infusion of

Hyperkalaemia continues to be a major hazard of mineralocorticoid receptor blockade in an effort to retard the progression of chronic kidney disease (CKD). In cardiac patients on mineralocorticoid receptor blockade, RLY-5016 which captures K(+) in the colon has been effective in reducing the risk of hyperkalaemia. This compound might be useful in CKD as well.

Background. Nephrologists develop their work in diverse scenarios. A training programme must qualify trainees to assist different kinds of problems. The aim of this study was to characterize patients and pathologies that Spanish nephrology fellows face while on-call. Methods. This is a descriptive study with clinical and demographic data gathered with a form by 10 nephrology fellows of five university hospitals of Madrid (Spain), throughout their in-hospital 24 h on-call shifts in February and March 2013. Results. We collected 409 episodes over 338 patients, through 72 shifts. Among these, 16.7% had previous normal renal function, 24.6% chronic kidney disease, 39.5% were on dialysis and 18.2% had a kidney transplant. Most of the consults came from the emergency room (35.9%) or the previous on-call team (13.7%). Afterwards, the most usual destiny was admittance to a nephrology department (32.8%) or discharge (20.5%). The most frequent reason for consulting was a decline in renal function (31.6%) and the second motive an infection. Thirty-four episodes (8.3%) were related to dialysis access problems. Medical treatment was prescribed in 79.2% of the cases, primarily fluids (47.2%) and antibiotics (42.2%). The fellow had to place a central venous catheter in 24 cases (5.9%). Renal replacement therapy was prescribed in 19.8% of the episodes. Conclusions. Specific renal reasons for consulting nephrologists are common, such as acute kidney injury or dialysis access complications. These patients benefit from a specialized approach to their problems. Clinical activities during in-hospital out-of-hours shifts are a priceless tool as part of the training programme of nephrology fellows.

Background. Renal replacement therapy (RRT) incidence has increased significantly in Sweden during the past decades. This study analyses variations in time and regional trends in RRT incidence in Sweden, adjusted for age and gender, focusing on the impact change in incidence during the last decade. Methods. Using data from the Swedish Renal Registry (SRR) (21 counties in Sweden, total population 9 million), we identified all incident subjects starting RRT from 1991 through 2010. Only individuals alive following 90 days of RRT start were included. Gender- and age-specific standardized RRT incidences on an annual and regional basis were calculated, and differences between counties and variations over time were examined. We compared the overall age and gender-adjusted RRT incidence rates for Sweden by calendar year. Furthermore, we also calculated the age and gender-adjusted RRT incidence in each county during two time periods (1991–1999 versus 2000–2010). Results. There were 20 172 new subjects treated with RRT between January 1991 and December 2010. The most common cause of end-stage renal disease (ESRD) was diabetes (24%) and hypertension/renal vascular disease (19%), followed by glomerulonephritis (16%). Sixty-four percent of new patients were male; the median age when commencing RRT was 66 years (10–90 percentiles; 39–80). The overall standardized RRT incidence reached its peak in 2000, and slowly decreased thereafter. A decrease in RRT incidence was observed over the study period in eight regions. The standardized RRT incidence varied between the different counties, from 0.82 to 1.19. Conclusions. Adjusted for demographic changes in the population, an overall decrease in RRT incidence was observed from the year 2000 onwards—suggesting that the previously reported steady increase in RRT incidence is coming to an end in Sweden. Noteworthy differences were found between counties and in 8 out of 21 counties, a decreased incidence of RRT was found. Further studies need to identify the factors that contribute to this decrease.

Although peritoneal dialysis (PD) is recognized as an effective renal replacement therapy (RRT) alternative to haemodialysis (HD), its prevalence is around 15% in most of the industrialized countries. In the French-speaking part of Belgium, PD is clearly underused with a prevalence of 8.7% in 2009. The main objectives of this work were to evaluate the nephrologists' perceived obstacles to PD implementation and reflect on possible actions towards PD development. A computer-based 33-item questionnaire was sent by e-mail to all nephrologists affiliated to the French-speaking association. Among 120 adult nephrologists targeted by this inquiry, 97 completed the online questionnaire (response rate 80.8%). Among them, 29% had little experience with PD (treating less than five patients) and 39% reported no specific training with this modality of RRT. However, 88% of responders claimed PD prevalence should be around 20–25%. Half of the responders would choose PD as a first RRT option if they required RRT for themselves. The three main reasons given to the low prevalence of PD were an easy access to HD, patient refusal and lack of nephrologist motivation. Almost all the nephrologists insisted on the need for a dedicated nursing team delivering an effective educational programme and PD management and care. They believe that PD could and should be implemented in Belgium. Enhanced nephrologist motivation and training in PD were identified as predominant factors to be upgraded, as well as patient education programmes.

Dialysis treatment, which is one of the methods of renal replacement therapy, is without a doubt one of the milestones in the development of medicine over the last 100 years. The method dates back to 1913, when John Abel, Leonard Rowntree and Bernard Turner of the USA succeeded in developing the first haemodialysis machine and performed the pioneering experiments on dogs. The first human haemodialysis session was performed in Giessen, Germany by Georg Haas in 1924. One year before that, Georg Ganter, also in Germany, performed the first peritoneal dialysis in human. However, it is the Dutch Willem Kolff who, by general consent, takes the credit for being the pioneer of haemodialysis. During the Second World War, he designed his own haemodialysis machine and used it to save the life of his patient with acute renal failure. After the war, another artificial kidney was designed in Lund, Sweden by Nils Alwall and was first used for haemodialysis in 1946. The Lund clinic went on to become one of the major European dialysis centres, where a number of Polish doctors were trained, later transferring their experience onto the Polish ground. The group included Dr Zygmunt Hanicki of the 2nd Department of Internal Medicine at the Medical University in Krakow, who, in the years 1949–57, having received the prototype of the machine from Nils Alwall, published the first Polish papers on haemodialysis treatment followed by the results of the laboratory studies [1, 2] (Figure 1). Fig. 1. Dr Zygmunt Hanicki (1919–95) and a copy of the title page of the first Polish article on the artificial kidney written by him ‘The Artificial Kidney. Possibilities of Application and Attempt to Explain the Mechanism’ published ... The first haemodialysis session in Poland was performed in Poznan in 1958 by the team of Dr Kazimierz Bączyk from the 2nd Department of Internal Medicine headed by Prof. Jan Roguski. The Krakow centre was the fourth dialysis centre to be established in Poland with the first haemodialysis session performed there on 15 June 1962 under the supervision of Assistant Professor Zygmunt Hanicki. Drs Zbylut Twardowski and Przemyslaw Hirszel, Jozef Bogdal, Adam Wiernikowski and the nurse Marcelina Pacut also participated in the session. Although Alwall's machine was the first artificial kidney used in the centre, later, along with its growth, newer haemodialysis machines were introduced to meet the current trends. Moreover, Prof. Hanicki, the Head of the clinic, started the building of an all-new dialysis unit at the Department of Nephrology [3] (Figures 2 and ​and33). Fig. 2. More than 100-year-old building with the first dialysis unit of the Department of Nephrology inside (photo by Janusz Ostrowski). Fig. 3. During one of the first haemodialyses in the 2nd Department of Internal Medicine at the Medical Academy in Krakow. First left: Dr Zygmunt Hanicki, the founder of the centre, nurse Marcelina Pacut, Dr Zuzanna Pączek and Dr Jozef Bogdal ... Following Prof. Hanicki's retirement, his student, Assistant Professor Wladyslaw Sulowicz took over as the Head of the Department to continue the development of the Department of Nephrology which today is one of the largest and most modern centres of nephrology in Poland, providing all kinds of renal replacement therapy on the highest level. Nowadays, the clinic comprises: the Conservative Management Unit, Dialysis Patient Unit, Post-Renal Transplant Unit, Peritoneal Dialysis Unit, Haemodialysis Unit (41 dialysis stations), Intensive Care Unit, operating theatre, Outpatient Department of Nephrology and Post-Renal Transplant Outpatient Clinic, as well as ultrasonography, X-ray, gastroscopy and rehabilitation facilities [4]. The ‘Progress in Nephrology and Transplantation’ Conference and Educational Course by ERA-EDTA held in Krakow on 10–12 May 2012, and attended by renowned Polish and foreign nephrologists was the capstone of the 50 years' activity of the Department of Nephrology at the Collegium Medicum of the Jagiellonian University in Krakow. Juliusz Slowacki theatre was the venue for the Opening Ceremony of the event. The official part included the speeches by Prof. Wladyslaw Sulowicz—the Chief Organizer, Prof. Wojciech Nowak—Vice-Rector for Collegium Medicum at the Jagiellonian University, Prof. Jacek Majchrowski—the President of Krakow, Prof. Raymond Vanholder—the President of ERA-EDTA, Prof. Goce Spasovski—ERA-EDTA Chairman for Continuous Education, Prof. Andrzej Wiecek—ERA-EDTA Secretary and Treasurer, Prof. Marian Klinger—Member of the Board of ERA-EDTA and the National Specialist for Nephrology and Prof. Jacek Manitius—the President of the Polish Society of Nephrology. To complete the official inauguration, the opening lecture titled ‘The Doctor's Mission in Modern Medicine’ was given by Prof. Tomasz Guzik (Figures 4 and ​and55). Fig. 4. Main building of the Jagiellonian University in Krakow, Poland (photo by Janusz Ostrowski). Fig. 5. Title page of the programme of the conference. The first part of the scientific session was of historical and recollective character with the lectures given by doyens of the Polish nephrology: Prof. Franciszek Kokot, Prof. Zofia Wankowicz and Prof. Zbylut Twardowski. The other subjects discussed during the remaining sessions of the first day included disturbances in calcium and phosphate in patients with renal failure (Prof. Goce Spasovski, Prof. Markus Ketteler, Prof. Tilman Drueke and Prof. Michal Myśliwiec), performance of dialysis in elderly patients (Prof. Marian Klinger), obesity-related glomerulopathy (Prof. Andrzej Wiecek), disaster-related complications in nephrology (Prof. Raymond Vanholder), renal replacement therapy in acute renal failure in the course of acute poisoning (Prof. Miroslav Mydlik), dialysis adequacy (Dr James Tattersall), anaemia therapy (Prof. Dimitros Tsakiris) and carnitine system in haemodialysed patients (Prof. Vincenzo Savica) (Figure 6). Fig. 6. Pioneers of dialysis treatment in Poland. First left: Prof. Zofia Wankowicz and Prof. Zbylut Twardowski (photo by Janusz Ostrowski). The first session on the second day of the conference concentrated on renal transplantation with lectures given by Prof. Przemyslaw Hirszel, Dr Paul Harden and Prof. Magdalena Durlik. In the session ‘Meet the Expert’, the current trends in anaemia therapy, new options in dialysis therapy, the methods of Ca-P metabolism control in Chronic Kidney Disease and the ways to increase the number of kidney transplantations were addressed. The chairpersons of the sessions were respectively: Prof. Jolanta Malyszko, Prof. Ryszard Gellert, Prof. Zbigniew Hruby and Prof. Ryszard Grenda. The speakers giving lectures in the last session included: Prof. Boleslaw Rutkowski (Epidemiology of Chronic Kidney Disease), Prof. Guido Bellinghieri (Pain and Quality of Life in Uraemic Patients), Prof. Andrzej Ksiązek (Hypertension in Dialysis Patients—Pathogenesis and Treatment) and Prof. Jacek Manitius (Atrial Fibrillation in Dialysis Patients—Pathogenesis and Treatment). The Progress in Nephrology and Transplantation Conference was yet another international event prepared by the Krakow Centre of Nephrology, which has been successfully managed by Prof. Wladyslaw Sulowicz for nearly 25 years. Since the conference was attended by numerous domestic and foreign leaders in the field of nephrology, its professional and organizational level was extremely high; it is fitting that the 50th anniversary of the first haemodialysis took place in the former capital city of Poland—Krakow [5].

We describe donor-transmitted Cryptococcus neoformans infection in a renal transplant recipient. The donor had no apparent risk factors for cryptococcal infection. The disease in the recipient, who did not receive prophylaxis, manifested relatively late at 50 days post-transplantation. We discuss the epidemiology and management of cryptococcal disease in solid organ transplant recipients and lessons learned from this case.

Idiopathic infantile hypercalcaemia (IIH) is an autosomal recessively inherited disease, presented in the first year of life with hypercalcaemia, precipitated by normal amounts of vitamin D supplementation. Recently loss-of-function mutations in the CYP24A1 gene, which encodes the vitamin D-metabolizing enzyme 24-hydroxylase, have been found in these patients. We describe a young man homozygous for a novel missense mutation (c.628T>C) of the CYP24A1 gene. He had suffered from severe hypercalcaemia in early childhood. At age 29 he presented with medullary nephrocalcinosis, chronic kidney disease (CKD) stage 2, microalbuminuria, mild hypertension and nephrogenic diabetes insipidus. He had mild hypercalcaemia and moderate hypercalciuria. As a novel finding, fibroblast growth factor 23 (FGF23) was elevated.

In 1996, the first European Union of Medical Specialists (UEMS) minimum standards programme in nephrology was published. Since then, medical practice in an expanded European Union (EU) has evolved significantly. These changes have prompted the UEMS Nephrology Section to update and review the programme on harmonization of nephrology training in the EU. Although directives of the EU indicate that a specialist from one EU member state must be recognized in all EU member states, the current practical implications of these directives are limited due to the important existing differences in the EU member states' training programmes. Although not exhaustive, the present document aims to profile a minimum common framework of nephrology training in the EU for both trainers and higher-specialty trainees. The nephrology programme addresses several topics, among them enrolment requirements, duration and organization of the training and a detailed description of the knowledge, competences, practical skills and attitudes necessary to become a specialist in nephrology. Whilst the development of a standard, pan-EU nephrology training programme is not realistic, the UEMS Nephrology section believes that this does not diminish the need for improving harmonization of training in the EU.

This figure shows the hexadactyly of feet and severe inflammation of the lower limbs of a 32-year-old Iranian female patient with Bardet–Biedl syndrome (BBS) who was referred to us with uraemic symptoms and metabolic acidosis. She had suffered from insulin-resistant type 2 diabetes mellitus for 2 years and moderate hypertension for 6 months. Her parents had noticed progressive decline in her vision and hearing since the age of 7 years. She had mild mental retardation. She had irregular menstrual periods but her secondary sex characteristics were normal. Her parents were not consanguineous. On physical examination, the patient was markedly obese with a body mass index of 31.4 Kg/cm2. She was dyspnoeic and often unwell. The blood pressure was 190/100 mmHg, axillary temperature 39°C, respiratory rate 22 beats/min, and heart rate 78 beats/min. Fundus examination revealed pigmentary retinopathy. Both lungs had coarse crackle in the basal field. Cardiac, abdominal and genital examinations were normal. On admission, her blood glucose level was 482 mg/dL, blood urea nitrogen 190 mg/dL and serum creatinine 12.6 mg/dL. Blood revealed metabolic acidosis. Ultrasonography also showed bilateral small-sized high echogenic kidneys without cyst and hydronephrosis. BBS is a rare autosomal recessive disease characterized by the abdominal obesity, mental retardation, pigmentary retinopathy, polydactyly and hypogenitalism. The degree of polydactyly, a prominent feature of this syndrome, varies from patient to patient, ranging from a wide fifth metatarsal or metacarpal to a complete sixth digit.

Background. When searching for renal literature, nephrologists must choose between several different bibliographic databases. We compared the availability of renal clinical studies in six major bibliographic databases. Methods. We gathered 151 renal systematic reviews, which collectively contained 2195 unique citations referencing primary studies in the form of journal articles, meeting articles or meeting abstracts published between 1963 and 2008. We searched for each citation in three subscription- free bibliographic databases (PubMed, Google Scholar and Scirus) and three subscription-based databases (EMBASE, Ovid-MEDLINE and ISI Web of Knowledge). For the subscription-free data- bases, we determined which full-text journal articles were available free of charge via links to the article source. Results. The proportion of journal articles contained within each of the six databases ranged from 96 to 97%; results were similar for meeting articles. Availability of meeting abstracts was poor, ranging from 0 to 37% (P < 0.01) with ISI Web of Knowledge containing the largest pro- portion (37%, 95% confidence interval (95% CI) 32-43%). Among the subscription-free data- bases, free access to full-text articles was highest in Google Scholar (38% free, 95% CI 36-41%), and was only marginally higher (39%) when all subscription-free databases were searched. After 2000, free access to full-text articles increased to 49%. Conclusions. Over 99% of renal clinical journal articles are available in at least one major biblio- graphic database. Subscription-free databases provide free full-text access to almost half of the articles published after the year 2000, which may be of particular interest to clinicians in settings with limited access to subscription-based resources.

Patients with anti-glomerular basement membrane (GBM) antibody-mediated GN usually present with rapidly progressive glomerulonephritis (GN) [1]. Patients may have isolated renal disease or may also have pulmonary symptoms [1]. The disease is caused by antibodies to the noncollagenous-1 (NC1) domain of the α3 chain of collagen IV, termed Goodpasture's antigen, in the majority of cases [2]. The antibody may cross-react in some patients with alveolar basement membranes and cause pulmonary hemorrhage (Goodpasture's disease) [1]. It is a rare cause of acute kidney injury, with an incidence of 0.5–1 cases per million populations [3]. Diagnosis may be based on the detection of circulating antibodies by immunoassays, and is usually confirmed by a renal biopsy. A renal biopsy shows linear staining of immunoglobulin (Ig) along the GBM by immunofluorescence. The autoantibody is generally IgG, although other Ig classes may be co-deposited. There are isolated reports of IgA or IgM alone being deposited on the GBM and also detected in the circulation [4]. The specificity of the antibody can be confirmed by western blotting [3]. False-negative serology antibody results may occur, generally in patients with isolated mild pulmonary disease [3]. False-positive results can occur in certain assays when circulating antibodies are generated to GBM antigens other than the NC1 domain of the α3 chain of collagen IV or in patients with polyclonal immune stimulation [3]. We report a patient who underwent a renal biopsy because of poorly controlled hypertension, nephrotic range proteinuria and rapidly progressive renal failure. The renal biopsy showed necrotizing crescentic GN superimposed on idiopathic nodular glomerulosclerosis (ING) and linear staining of IgG along the glomerular capillary walls. Circulating anti-GBM antibodies were found to be absent by standard immunoassays. This case illustrates the complexity of renal lesions that may coexist. Implication for establishing the diagnosis of anti-GBM-mediated GN and the need for renal biopsy in making specific diagnosis are also discussed. Case history A 79-year-old man presented with complaint of persistent lower extremity edema, not relieved by diuretics. He had a history of poorly controlled hypertension, nephrotic range proteinuria and rapidly progressive renal failure with rising of serum creatinine from baseline 150.0 to 266.0 mmol/L within 2 months. His past clinical history was significant for hyperlipidemia, chronic obstructive pulmonary disease, benign prostatic hyperplasia, osteoarthritis and hyperparathyroidism. The remaining review of systems was negative. There was a history of smoking for 40 years. There was no history of diabetes mellitus or glucose imbalance. On physical examination, he appeared acutely ill. His blood pressure was 203/90 mmHg, respiratory rate 15/min, pulse rate 79/min and temperature 36.1°C. There was a 2+ pitting edema of the lower extremities. The remaining physical examination was unremarkable. Laboratory studies demonstrated blood glucose levels to be 6.0 mmol/L, sodium 144 mmol/L, potassium 4.4 mmol/L, chloride 107 mmol/L, bicarbonate 29 mmol/L, calcium 2.0 mmol/L, phosphorus 1.7 mmol/L, blood urea nitrogen 7.6 mmol/L, creatinine 266.0 μmol/L and total serum proteins 53.0 g/L with gamma globulin 30.0 g/L. Hemoglobin A1c was 0.06 hemoglobin fraction. His lipid profile was within the normal range. Serum anti-nuclear antibody was negative, anti-double stranded DNA was

Some degree of peripheral oedema is not uncommon following renal transplantation. Bilateral peripheral oedema is seen in the context of congestive heart failure, delayed graft function with extracellular volume expansion or nephrotic syndrome due to glomerular disease. Mild unilateral peripheral oedema is also often seen, typically early after surgery and on the transplanted side. In these cases, it is usually assumed that some form of damage to the lymphatic ducts has occurred during transplant surgery. The swelling is usually mild and often settles over time. However, severe peripheral oedema on the contralateral side is uncommon, especially if deep venous thrombosis has already been excluded. We report such a case, which led to an unusual diagnosis. We also provide a brief review of the relevant literature and discuss recent insight into possible mechanisms and pathways.

Infection is a leading cause of morbidity and mortality among haemodialysis patients. Some of the risk factors specific to this population include repeated access to the blood stream through venous cannulation for dialysis as well as a higher prevalent usage of prosthetic materials like haemodialysis catheters and arteriovenous grafts. In addition, defects in immunity and phagocytosis also contribute to the increased risk of infection. Both iron overload [1] and its treatment, desferrioxamine (DFO), predispose haemodialysis patients to infections [2, 3]. We describe here a fatal case of Cunninghamella bertholletiae infection in a haemodialysis patient with transfusional iron overload while receiving DFO.

The reported incidence of transplant renal artery stenosis (TRAS), as high as 23% in earlier decades [1], ranges between 1.2 and 3.9% in more recent reports [2–5]. TRAS is a frequent cause of refractory hypertension and allograft dysfunction [5], but it is often treatable with percutaneous angioplasty. Therefore, its early recognition is critical. We describe the incidence of TRAS in our center over a 10-year period and report a case of TRAS to illustrate the complexity of the diagnosis in patients with slowly recovering graft function, multiple renal arteries and high immunologic risk for rejection. We highlight the utility of a novel non-contrast renal magnetic resonance angiography.

Gastrointestinal side effects affect ∼20% of renal transplant recipients [1]. Among such side effects, diarrhoea is common [2] but under-recognized [3]. Diarrhoea may relate to immunosuppressive drugs or infectious complications. The latter may be caused by one of the usual microbial pathogens that also cause gastroenteritis in immunocompetent patients, such as campylobacter, salmonella or viruses. Cytomegalovirus (CMV) colitis, for example, is seen as a cause of diarrhoea, usually within the first one or two post-transplant years. Once these usual suspects have been excluded, the clinician is left with a long differential diagnosis of other causes of diarrhoea in the immunosuppressed host. We describe the interesting case of a 49-year-old renal transplant recipient who presented with an unusual cause of diarrhoea 2.5 years after transplantation.

Autogenous arteriovenous fistulas (AVFs) are considered the most reliable long-term vascular access in patients undergoing haemodialysis. Although AVFs generally require fewer interventions than arteriovenous grafts (AVGs) to maintain patency, some sites of venous stenosis account for a large portion of repeated interventions. A particularly troublesome site within brachiocephalic AVFs is the cephalic arch. Cephalic arch stenosis (CAS) has been implicated in 19–77% of brachiocephalic fistula failures [1]. The cephalic arch has a unique architecture. In addition to containing a high concentration of valves and having a steep angulation, it crosses multiple tissue planes, bridging the superficial and deep venous systems while being tethered to rigid extravascular structures. These factors combine to make the cephalic arch particularly vulnerable to the development of stenotic lesions, as changes in vessel compliance produce turbulent flow. When an anastomosis is created between the brachial artery and the cephalic vein, the flow within the cephalic vein increases and the vessel starts dilating. However, the tissues surrounding the cephalic arch preclude its expansion, so that the cephalic vein narrows as it approaches its junction with the central veins. This sudden reduction in the circumference of a high-flow pathway results in an inflow–outflow mismatch, potentiating turbulence and the increased shear stress associated with it [1, 2]. When a CAS occurs, the management is not easy. Angioplasty of stenotic lesions involving the cephalic arch has limited effectiveness, which led investigators to seek surgical alternatives to treat these lesions and to preserve current fistula [1]. The option for cephalic vein transposition (CVT), described by Chen et al., involves surgical revision to redirect the blood flow to the adjacent patient veins. The surgical procedure entailed transecting the healthy portion of the cephalic vein distal to the stenotic segment in the arch, transposing and anastomosing it to the upper basilic [2] (Figure ​(Figure11). Fig. 1. Illustration of the cephalic vein transposition technique. We present the experience of our centre with upper arm CVT procedures in three haemodialysis patients who underwent haemodialysis treatment in the haemodialysis unit of Centro Hospitalar de Setubal E.P.E. Two of the 3 cases did not have the possibility of endovascular treatment. In these cases CVT to basilic vein made possible the preservation of vascular access. Both accesses are patents to date, 6 and 9 months, respectively. In the other case, the CVT allowed the reduction of percutaneous transluminal angioplasties (PTAs)/access-year in a patient with frequent recurrent CAS (requiring angioplasty in

Electrolyte abnormalities are very common problems in clinical practice, and if chronic, their management can be difficult. Hypokalemia, defined as a serum potassium level 20% of hospitalized patients have been reported to have some degree of hypokalemia [1]. Hypomagnesemia is also common and has been observed in as many as 50% of critically ill and Intensive Care Unit patients [2]. Patients with severe electrolyte deficiencies may be treated with intravenous (IV) or oral replacement regimens. We discuss a case in which a patient was treated for 16 years with an IV electrolyte replacement regimen. Using a stepwise approach, we were able to stop the IV replacement therapy and transition the patient to an oral electrolyte replacement.

In daily practice hypokalaemia is frequently observed. It can be accompanied by various adverse events and can even be life threatening. Frequent causes are intestinal and urinary loss, i.e. diarrhoea or use of diuretics. Glycyrrhizin-containing substances, such as liquorice, are a well-known but rare cause of hypokalaemia. They can induce an apparent mineralocorticoid excess-like syndrome, often accompanied by hypertension, metabolic alkalosis, sodium retention and renal potassium wasting [1]. We will discuss a case of liquorice-induced hypokalaemia causing serious electrolyte disorders and severe clinical symptoms.

The Balkan Cities Association of Nephrology, Dialysis, Transplantation and Artificial Organs (BANTAO) was born in Ohrid (Figure 1), Republic of Macedonia, on 9 October 1993 at the first Congress of the Macedonian Society of Nephrology, Dialysis, Transplantation and Artificial Organs (MSNDTAO) [1]. At that very moment, bloody wars raged in former Yugoslavia. Fratricide, destruction and cruelty were the norm. Nevertheless, in spite of the hatred and political intrigue, Balkan nephrologists were willing to cooperate with one another. The war in Yugoslavia created hate among people and between the newly established countries. There were even problems with the recognition of the names of the new countries. To overcome this, the nephrologists in the Balkans decided to apply the ancient principle of using the names of the cities, instead of countries, in founding BANTAO (Figure 2). So it came into being as the Balkan Cities Association of Nephrology, Dialysis, Transplantation and Artificial Organs. The idea was to create a nephrology association from the Balkan cities and form a collaboration across the iron gates of borders and beyond the perverse and bloody political nationalistic ideology. The main goal of BANTAO was to promote scientific and technical cooperation for renal diseases and artificial organs among cities of the Balkan Peninsula and with the international nephrology community. It was important to create opportunities for the exchange of expert experience and knowledge and to take part in collaborative projects. This was a rare opportunity to transcend divisions, obstructions and distrust in this unfortunate and turbulent part of Europe. A task force was formed from representatives of different cities from the Balkans: S. Kodra (Tirana), D. Nenov (Varna), Z. Kirjakov (Sofia), Gj. Masin (Skopje), M. Polenakovic (Skopje), F. Akcicek (Izmir), E.J. Dorhout Mess (Izmir), Lj. Djukanovic (Belgrade), A. Radmilovic (Belgrade) and S. Strahinjic (Nis). Momir H. Polenakovic, President of the MSNDTAO, was elected chairman of this task force. Some Western European nephrologists (H. Klinkman, J. Vienken, E.J. Dorhout Mees, D. Falkenhagen and P. Ivanovich), the European Society of Artificial Organs (ESAO) and the International Faculty for Artificial Organs (IFAO) have greatly assisted our initial efforts to establish the BANTAO. The first BANTAO Congress was held in Varna, Bulgaria from 22 to 24 September 1995 (when the Balkan wars were still at their height) under the presidency of D. Nenov (Varna). The congress in Varna was successful, with >80 papers presented by nephrologists from the Balkans and other European cities. The first BANTAO Congress had a positive impact on the nephrology community in Europe. Our Spanish colleague, the late F. Valderrabano, published a congress report [2]: ‘Nephrologists of the Balkan countries meet across political frontiers and war fronts— an example to politicians! BANTAO: a new European medical association overcomes political obstacles. This is an extraordinary initiative of nephrologists working in cities throughout the Balkan countries who have been able to create a scientific association and to organize its first congress, despite the boundaries of war, the rupture of international relations and other serious political problems which emerged in the Balkan countries after the disappearance of the former Republic of Yugoslavia. The main goal of BANTAO is to promote scientific and technical cooperation in the field of renal diseases and artificial organs between the Balkan cities. This goal will be achieved not only through a periodical congress, but also through lecturer exchange, fellowship exchange, scientific research methods exchange, joint meetings and courses, publications and cooperation in the field of renal transplant. BANTAO wants to work closely with other international societies and especially with EDTA-ERA. BANTAO represents an extraordinary initiative and should receive both scientific and economic support from the EDTA-ERA. The exceptional effort of collaboration shown by our Balkan colleagues, who have been able to carry out scientific activities in extremely adverse human conditions, is an example to the European nephrological community, which should not hesitate to offer all possible help to this new association’. As Valderrabano suggested, ERA-EDTA (four supported CME courses) and also ISN (two events) have given encouragement and practical help to the BANTAO

About 85–90% of children with idiopathic nephrotic syndrome responds to steroid therapy while the remaining 10–15% fails to respond and is defined as steroid-resistant nephrotic syndrome (SRNS). The histopathological lesions in SRNS are minimal changes, focal and segmental sclerosis (FSGS) and mesangial proliferation. The response to cyclosporine alone or in combination with prednisolone therapy is variable. Proteinuria in FSGS in some patients is associated with a permeability factor (PF). Galactose has been shown to bind with PF [1] and prevents its interaction with podocyte glycocalyx, and oral administration of galactose may lead to reduction of proteinuria [2]. In view of this, we report an observational case study where two separate courses of oral galactose were given to three children with steroid-resistant idiopathic nephrotic syndrome with FSGS in order to reduce proteinuria and increase serum albumin levels. The patient characteristics are presented in Table ​Table1.1. They had generalized oedema, urinary protein/creatinine ratio of >200 mg/mmol (>2 mg/mg), hypalbuminaemia serum albumin 5.18 mmol/L (>200 mg/dL). The children did not achieve remission with prednisolone (2 mg/kg/day) therapy administered for 4 weeks. Kidney biopsy tissues, examined in light and immunofluorescent microscopy, demonstrated focal and segmental glomerulosclerosis. The patients were tested for C3, C4, ANA, anti-ds DNA, HIV, Hepatitis B surface antigen and tuberculin test. Chest radiographs were normal. NPHS2 gene analysis showed R229Q polymorphism in Case 1. The protocol of the study was approved by the Institute Ethics Committee. Table 1. Patient characteristics The children were treated with cyclosporine (4–5 mg/kg/day in two divided doses), prednisolone (1.5 mg/kg, single dose alternate days with gradual taper to a minimum of 0.5 mg/kg) and ramipril (0.2 mg/kg/day, single dose). Furosemide (1–2 mg/kg/day) was given to reduce oedema. The patients received cyclosporine, prednisolone and ramipril for 11–14 months duration and had stable serum creatinine levels. Doses of cyclosporine and ramipril remained unchanged. Patients did not achieve remission as urine protein/creatinine ratios of >200 mg/mmol (>2 mg/mg) persisted. Thereafter, oral d-galactose (Manufactured by Hi Media Laboratories Pvt. Ltd., Mumbai, India) was added at a dose of 0.2 g/kg/dose, twice daily. The patients were followed regularly at a 30-day interval during the first course of galactose trial given for 90 days. After an interval of 90 days in Case 1, 60 days in Case 2 and 105 days in Case 3, a second course of galactose treatment at the same doses was reinstituted for 30 days. The changes in urinary protein/creatinine ratios and serum albumin levels are shown in Figure 1. In all three patients, urinary protein/creatinine ratios decreased (by 37.9, 50.6 and 77.5%), and serum albumin levels increased (by 56, 72 and 23.3%) at 90 days from their pre-galactose values. After discontinuation of galactose, urine protein/creatinine and serum albumin values showed deterioration at 120 days. After the second course of galactose, there was again a reduction of urinary protein/creatinine ratios by 46.5% in Case 1, 37.5% in Case 2 and 25.7% in Case 3 and an increase in serum albumin levels in comparison to their values 30 days before. However, parameters became again abnormal after discontinuation of galactose. No adverse events were noted following galactose therapy. Fig. 1 Urine protein/creatinine ratios and serum albumin levels during the two periods of galactose therapy and the interval period. It showed gradual reduction in urine protein/creatinine ratios and rise in serum albumin values during, deterioration after discontinuation ... The galactose had a beneficial effect in all three patients. The galactose helps in reduction of proteinuria as it directly binds with PF and prevents interaction of PF to galactose residues of podocyte glycocalyx. Subsequently, the galactose–PF complex is cleared from plasma by hepatocytes or macrophages [2]. De Smet et al. [3] in one adult and Kopac et al. [4] demonstrated the effect of galactose in reduction of proteinuria and its benefit persisted for about 3 months in one case. In our cases, the effect lasted as long as galactose was given; indicating that a continuous treatment is necessary to maintain its positive effect on proteinuria. Our patients had no remission with cyclosporine and prednisolone therapy given for a sufficient period. Galactose had lead to reduction of proteinuria and increase in serum albumin during the treatment period. Recently, Sgambat et al. [5] observed no significant difference between pre- and post-treatment mean urine protein/creatinine ratios after 16 weeks of galactose administration, and the authors concluded that it failed to improve proteinuria. In our study, though no patient achieved complete remission (urine protein/creatinine ratio

A 42-year-old male with a history of end-stage kidney disease secondary to diabetes mellitus type 1 received a deceased donor simultaneous kidney/pancreas transplant 10 months prior to presentation. The patient had prompt graft function and no other complications. He presented with gross hematuria and kidney allograft dysfunction with serum creatinine elevation from baseline of 114.92 to 221 µmol/L (1.3 to 2.5 mg/dL). Ultrasound and abdominal computed tomography were normal. Polyomavirus and cytomegalovirus (CMV) polymerase chain reaction (PCR) were negative. A kidney biopsy showed patchy necrotizing and vaguely granulomatous tubulointerstitial inflammation (Figure 1A). The infiltrate consisted of neutrophils, macrophages and lymphocytes with abundant epithelial cell destruction. Occasional epithelial cell nuclei had glassy chromatin suggestive of viral cytopathic effect (Figure 1B). Immunohistochemical staining for C4d, SV40, CMV and HSV was negative, while staining for adenovirus showed strong reactivity. Positivity of adenovirus PCR of more than 1 000 000 copy/mL confirmed the diagnosis of adenovirus tubulointerstitial nephritis. Immunosuppressive medications were reduced and one dose of cidofovir and intravenous immunoglobulin (IVIG) was given. Adenovirus PCR decreased to 175 000 after 1 week, and was no longer detected after 1 month. Creatinine gradually decreased to baseline over 3 months. Fig. 1. (A). Lower power image showing patchy tubulointerstitial inflammation (H&E, ×40). (B). Tubular epithelial cell necrosis (arrow heads), and a glassy viral inclusion (arrow) (H&E, ×400). Adenoviruses are non-enveloped double-stranded DNA viruses. Such virus presents as a self-limited respiratory, gastrointestinal and conjunctival disease in immunocompetent patients. In kidney transplant recipients, it manifests as allograft dysfunction, and hemorrhagic cystitis, but can result in severe fatal cases [1]. Infection is rare with an incidence rate of around 4% in kidney transplant recipients [2]. Infection can be de novo, or through reactivation of a latent infection of the recipient or from the allograft. Adenovirus serology is not routinely checked before transplantation, but serology mismatch might be a risk factor for infection [1]. The presence of patchy necrotizing infection, large nuclei with basophilic glassy inclusions and negativity of polyoma and CMV serology should suggest additional work-up for adenovirus, especially in the setting of hemorrhagic cystitis. A PCR offers a highly sensitive tool to confirm the infection and monitor the response of treatment [3]. Management starts with reduction of immunosuppressive medications. Severe cases might require one or two regimens of cidofovir, and administration of IVIG. Outcomes of reported cases showed that clearance of adenovirus viremia occurs within 1–3 weeks [2], and that there is an improvement in kidney allograft function to baseline or near baseline in the majority of cases [4].

Dengue is a common viral infection of the tropics caused by four serotypes of Dengue virus belonging to the family of flavivirus. Clinical presentation of symptomatic Dengue virus infections can be wide, from a mild febrile illness to a life-threatening shock syndrome. We present a case of a young male with unusual presentation of Dengue as acute renal failure secondary to rhabdomyolysis.

Sir, Renal amyloidosis secondary to familial Mediterranean fever (FMF) is one of the common causes of nephrotic syndrome and chronic kidney disease in Turkey [1]. Colchicine is a microtubule-depolymerizing drug widely used for the treatment of gout which may prevent the development of secondary amyloidosis. In end-stage renal disease (ESRD), although the dose of colchicine is suggested to be reduced, there is limited information on efficacy and safety [2]. Inappropriately high doses or co-prescription of CYP3A4 or P-glycoprotein inhibitors have been reported to cause serious adverse effects, including death [3–7]. Herein, we present a case of colchicine-induced rhabdomyolysis after using clarithromycin, a macrolide antibiotic and a potent inhibitor of CYP3A4 and P-glycoprotein ABCB1. A 40-year old male patient on maintenance haemodialysis was admitted with recently developed fatigue, anorexia, headache, dizziness, diffuse myalgia and gastrointestinal symptoms including epigastric pain, diarrhoea and bloating. He presented with FMF in childhood (with frequent attacks of fever and abdominal pain with arthritis) and had developed secondary amyloidosis 10 years previously and ESRD 6 months previously. His long-term medication was colchicine 0.5 mg twice daily, doxazosin 4 mg once daily and 40 mg furosemide on non-dialysis days and sevelamer 1600 mg three times a day. A further history revealed that the patient had recently been diagnosed with acute sinusitis and was prescribed clarithromycin 500 mg twice daily in another hospital a week beofore. On his initial examination the patient's blood pressure was 100/60 mmHg, he was in a euvolaemic state and had no significant finding except diffuse tenderness, but there was no rebound on abdominal palpation. In his biochemistry, his creatine kinase (CK)(5732 U/L- 9035 U/L) and transaminase levels (ALT:110 U/L, AST:309 U/L) were elevated and raised upon follow-up. Due to high CK and transaminases, colchicine-induced rhabdomyolysis was diagnosed and colchicine discontinued. The patient's pain subsided 3 days after discontinuation of colchicine. An EMG was performed because of high levels of CK to exclude the diseases causing myopathie. During outpatient follow-up, the patient's transaminases and CK returned to normal levels and his EMG was normal. After complete recovery, the patient started colchicine 0.5 mg/day again without recurrence of symptoms.

We have read the interesting case of Lyme disease-related cryoglobulinaemic membranoproliferative glomerulonephritis (MPGN) reported by Schneider et al. [1]. After several scarce cases of MPGN secondary to Lyme disease reported to date [2–5], this case report is intriguing due to the concurrence of type II cryoglobulinaemia (CG). The authors support the view that MPGN ‘is to be seen as indirectly Borrelia-related through CG-mediated complement activation’, based on the characteristic finding of subendothelial deposits of crystalloid material as well as the ‘full-house’ histological pattern. The presence of CG in Lyme disease-associated MPGN might indeed be revealing of potential pathogenetic mechanisms not evident in the cases reported earlier. Type I MPGN is an IC-mediated glomerulonephritis caused by the deposition of IgG and C3, involving activation of the classical complement pathway, triggered by an inciting event, such as an infection or a neoplastic or autoimmune disease. In addition, type II CG is caused by the development of IgM–IgG immune complexes (ICs) and is associated with acute or chronic infections and neoplastic and autoimmune diseases. Lyme disease, on the other hand, is a chronic infection inciting by itself IC formation, as evidenced by its concurrence with other IC-mediated manifestations, such as Guillain–Barre syndrome, acoustic mononeuritis and serositis and with increased levels of rheumatoid factor (anti-IgG IgM), etc. [2]. The specific IgM response peak in Borrelia burgdorferi infection, which leads to polyclonal activation of B cells and the formation of ICs, as well as cryoglobulins/IgM rheumatoid factor, takes place several weeks after the initiation of the infection. Later, the specific IgG response develops against an increasing array of spirochetal polypeptides and non-protein antigens, eventually leading to spirochete lysis by the classical complement pathway. Therefore, our understanding is that all three of these conditions are manifestations of the infection-induced immunostimulation and the resulting formation of ICs, which is why the optimal treatment seems to be the combined use of antibiotics and immunosuppressive drugs, such as corticosteroids [1–4, 6]. The prominent common denominator involved in the pathogenesis of this pathology is the activation of the classical complement pathway. In this constellation of manifestations, we think that the infectious as well as the autoimmune parts are closely intercalated and, therefore, indistinguishable. Regarding the ‘full-house’ histological pattern, despite the fact that an MPGN pattern associated with autoimmune diseases is indeed often characterized by the deposition of multiple immunoglobulins and complement proteins (IgG, IgM, IgA, C1q, C3, kappa and lambda light chains), the exact pathophysiological role of C1q immune deposits in propagating glomerulonephritis is yet to be elucidated, and it is questionable whether it represents a pathognomonic finding or just a manifestation of the activated classical complement pathway. To this context, the presence of C1q deposits does not reveal a causative relation of MPGN with CG and, therefore, we believe that such an association is actually speculative, an opinion which is further supported by the fact that the same diagnosis and histological findings were documented in the cases reported earlier even in the absence of CG.

The haemolytic-uraemic syndrome (HUS), a thrombotic microangiopathy, occurs often secondary to an infection due to Shiga-toxin-producing Escherichia coli (E Coli), the most threatening complication being neurological involvement [1]. Plasmata exchange has been shown to have some efficiency [2, 3]. Use of complement cascade-blocking antibody eculizumab is becoming the first-line treatment in the severest cases [4]. At the onset of spring in Europe in 2011, IgG depletion through immunoadsorption was reported to be effective in treating the severe neurological complications of HUS in adults [5, 6]. In October 2011, a 26-month-old girl presented with HUS requiring dialysis, with hepatic, pancreatic and cardiac involvement, seven days after the onset of E. coli enteritis. Eculizumab was administrated to treat severe neurological symptoms (unresponsiveness, comatose state, hypertonic quadriplegia, Glasgow score 8/15) due to bilateral thalamic infarctions seen on MRI one day after the onset of HUS (Figure 1). On day 3, a session of plasmapheresis was performed followed by a second eculizumab infusion because of the absence of neurological recovery. Despite this treatment and a slight increase in the platelet count, the patient's neurological status worsened, with recurrent occipital seizures and the need for mechanical ventilation. A third eculizumab infusion was carried out on day 8. Diffusion MRI sequences showed new lenticular lesions associated with right occipital-cortex lesions. In this life-threatening situation, we decided to perform IgG depletion by immunoadsorption as a rescue therapy (six sessions over five days, starting on day 9). A moderate clinical improvement (cessation of seizures, extubation on day 14) was associated with a rapid improvement in the disease activity (platelet count >150.109/L on day 16). Dialysis was stopped on day 13. The patient was discharged on day 60 with severe neurological sequelae: absence of eye contact, quadriplegia and major cortical and subcortical atrophy on MRI. The creatinine clearance rate was 45 mL/min, with 2 g/L proteinuria. Screening for complement function abnormalities (CFH, CFI, MCP, C3 and C4) and anti-CFH antibodies was negative. Three months later, surprisingly, the patient recovered her previous level of motor function with an independent walk and previous language skills. The creatinine clearance rate stayed at 45 mL/min. Thus, in this child with severe neurological HUS, eculizumab and immunoadsorption treatment were associated with an unexpectedly favourable evolution in the medium term. Fig. 1. Course of a 26-months-old girl with severe post-diarrhoea HUS treated by administration of eculizumab and by immunoadsorption. (a) day 1 MRI: diffusion-weighted image, axial view: marked bilateral hypersignal in thalami. (b) day 8 MRI: diffusion-weighted ... The effectiveness of plasmapheresis is controversial [2, 3], and despite encouraging results with eculizumab [4], this treatment is not effective in all forms of post-diarrhoea HUS with severe neurological involvement. We suggest that immunoadsorption, considered a therapeutic option in severe neurological HUS in adults, also be used as a rescue treatment in children. However, studies and protocols are needed to determine the relevance of the association between the two treatments and their timing in neurological forms of post-diarrhoea HUS in children.

Plasma cell disorders are important in the differential diagnosis of acute kidney injury and of renal impairment with proteinuria. One or more of several mechanisms can be involved, such as cast nephropathy, deposition of monoclonal immunoglobulins, formation of amyloid fibrils, hypercalcaemia, hyperuricaemia and a variety of tubular syndromes. Various tests, such as serum electrophoresis and immunofixation, assays for serum immunoglobulins and free light chains and tests for urinary paraproteins, also known as ‘Bence Jones protein’, are routinely employed in clinical practice. Scribbling these two words on a laboratory form (or ticking a box on a computer screen) raises questions: what is being tested and who is ‘Bence Jones’. Does this eponym honour one physician or two, or perhaps a patient? Here, we provide some insights into the history of this commonly used eponym and aim to put it into context.

Sir, In contrast to the reported poor prognosis of haemodialysis patients, the article by Heaf et al. [1] published in a recent issue of Clinical Kidney Journal reports the remarkable long-term survival of one such patient. We too have a similar story and can confirm that long-term survival is entirely possible. This may offer hope and allay the fears and depression that accompany the prospect of life-long dialysis. Our patient was a woman, born in 1944, who started treatment at the age of 26 for end-stage renal disease due to glomerulonephritis. Our patient received a kidney transplant in 1981, but unfortunately this did not function and she was never able to discontinue dialysis, even for one treatment session. The graft was ultimately removed after 1 week. Like Heaf et al.'s patient, ours underwent total parathyroidectomy with reimplantation in her right forearm, and calcium and PTH levels are now under control with 1 μg calcitriol weekly. What is even more remarkable is that her arterovenous fistula, which was inserted when she first started dialysis, is still working perfectly and is still used to administer treatment three times a week without any problems or signs of malfunction. Despite severe arthropathy and coronary artery disease (she has refused coronary angioplasty), her quality of life is good since she is reasonably independent in her everyday life and still lives at home with her husband. In September 2012, our patient celebrated 40 years of uninterrupted dialysis treatment with the entire dialysis staff, and an article appeared in a local paper to commemorate the event (http://ricerca.gelocal.it/tribunatreviso/archivio/tribunatreviso/2011/09/28/TP5PO_TP505.html). Interestingly, our patient has demonstrated the two essential qualities mentioned by Heaf et al.: ‘good compliance and a will to live’. In our opinion, it is important that these cases are made known, to demonstrate that although it may not be the rule, it is possible to survive for such long periods of time on dialysis and experience a good quality of life.

Anti-glomerular basement membrane (GBM) glomerulonephritis is characterized by rapidly progressive glomerulonephritis (RPGN) with anti-glomerular basement antibodies. Although the underlying pathogenesis is not completely understood, factors such as smoking, cocaine, silica or mechanical stress are known to induce auto-antibody production. Moreover, studies have reported that radiotherapy may trigger auto-immunity: some cases revealed increased immune response to tumour antigens after local radiotherapy. Here, we describe a case of anti-GBM glomerulonephritis which developed post-radiotherapy for early prostate cancer. A 68-year-old Japanese male was admitted to our hospital for acute kidney injury (AKI) with serious rectal bleeding, which was thought to be the adverse effects of previous radiotherapy for prostate cancer. He had been well until he complained of gross haematuria, with increasing prostate-specific antigen (PSA) levels (8.74 ng/mL)(8.74 μg/L).

Infection has been well documented to cause glomerulonephritis (GN), with Streptococcus being the most common pathogen. However, the pattern of the disease has changed over recent decades [1–3]. The bacterial flora now comprises Staphylococcus and Gram-negative strains, and the focus of infection is wider than the throat and the skin [1]. GN secondary to osteomyelitis has rarely been reported. We report a case of immune complex-mediated diffuse proliferative GN with acute on chronic renal failure, superimposed on diabetic nephropathy due to osteomyelitis caused by Enterobacter cloacae.

Malignant hypertension (MHTN) is diagnosed when a patient presents with accelerated hypertension and multiorgan compromise including severe retinopathy. The renal manifestations may be oliguric renal failure or rapidly progressive renal failure. Oliguria in MHTN occurs as a consequence of malignant nephrosclerosis, microangiopathic haemolytic anemia, polyarteritis nodosa, lupus, acute cortical necrosis and scleroderma. However, acute kidney insufficiency (AKI) may be seen in the absence of systemic disease or of nephropathy. The clinical presentation of anuria with MHTN is rare, and in such situations renal recovery is unlikely. There are few case studies reporting reversible renal failure in MHTN [1–16]. A literature search supports the view that the entity of reversible anuric renal failure in MHTN is recognized by early clinical presentation (with anuria/oliguria), the presence of normal sized kidneys, normal main renal arteries and kidney biopsy without significant vascular changes. Herein, we report two such cases with anuria due to MHTN who recovered after remaining on haemodialysis for an average 2 months.

Henoch–Schonlein purpura (HSP) is a systemic vasculitis affecting the small blood vessels of the skin, the gastrointestinal tract and the kidneys. HSP typically affects children and is self-limiting. Less commonly it presents in adults. Several triggers for HSP have been recognized, including infections, medications and malignancy. This report describes a patient presenting with HSP who was found to have an underlying malignancy and highlights that in adults presenting with HSP a careful search for an underlying cause should be undertaken.

Human polyomaviruses have entered the domain of clinical decision-making in renal transplantation and this has coincided with the use of more potent immunosuppressive regimens. BK polyomavirus has predominated, resulting in nephropathy and ureteral strictures with the potential for graft loss [1]. JCV is a type of human polyomavirus, named with the initials of the patient from whom the virus was first isolated. JC polyomavirus is known to cause progressive multifocal leukoencephalopathy (PML) which has been reported in the renal transplant population [2]. Polymerase chain reaction (PCR) screening for BK polyomavirus in the early post-transplant period is routinely performed worldwide but is not known to occur for JC polyomavirus.

A 72-year-old Caucasian man was admitted for dyspnoea and weight loss. He had hypoalbuminaemia (1.6 g/dL) and nephrotic proteinuria (18 g/day), mild renal failure, anaemia and thrombocytopaenia. Physical examination, abdomen ultrasound and computerized tomography scan showed splenomegaly (Figure 1a and b), pleural effusion, oedema in the lower extremities, laterocervical, axillary, ilo-mediastinic, abdominal lymphadenopathy and kidneys enlargement with changed parenchymal echogenicity. Axillary lymph node biopsy showed a non-necrotizing granulomatous process with epithelioid cells and rare giant cells. We performed bone marrow aspiration with diagnosis of B lymphoproliferative process. Search of amyloid in abdominal fat, immunological and virological screening, tumour markers and monoclonal paraprotein were negative. Due to worsening of renal function, the patient began haemodialysis treatment with regression of dyspnoea and significant reduction of pleural effusion and legs oedema. Renal biopsy showed a lymphoproliferative process. On pathological examination, normal kidney architecture was extensively replaced by lymphoma with a diffuse pattern (Figure 2). The neoplasm was composed predominantly of small lymphoid cells with mildly irregular nuclear contours and moderate cytoplasm. The neoplastic cells were CD20+, CD5−, CD10−, CD23− and bcl-2+ve (Figure 3a and b). We made a diagnosis of marginal zone lymphoma Stage IV. Following CVP chemotherapy (cyclophosphamide, vincristine, prednisone), his renal function gradually improved and it was possible to stop dialysis. The creatinine fell to 132 μmol/L and the nephrotic syndrome was in remission (albumen 31 g/L). There has been a progressive increase in the incidence of lymphomas seen over recent decades. Following the improved prognosis and longer survival of lymphoma patients, it is possible to observe more frequently the solid organ involvement. Kidney involvement can be related to obstruction, treatment-induced toxicity and, with more interest for nephrologists, to (i) direct infiltration, (ii) association with kidney malignancies (mostly renal cell carcinoma or urothelial tumours) and (iii) association with glomerular diseases (mainly minimal change disease). Primary infiltration is rarely seen [1]. Fig. 1. (a) Computerized tomography scan abdomen: huge splenomegaly (green arrow) and enlarged right kidney (red arrow). (b) Computerized tomography scan abdomen: enlarged left kidney (red arrow). Fig. 2. Renal biopsy: the normal kidney architecture is extensively replaced by a lymphoma with a diffuse pattern; the neoplasm is composed predominantly of small lymphoid cells with round or slightly irregular contours and moderate cytoplasm. In some fields, ... Fig. 3. (a) Renal biopsy: the neoplastic cells are CD20+ (immunohistochemical stain with haematoxylin counterstain for CD20, ×40). (b) Renal biopsy: the neoplastic cells are bcl-2+ (immunohistochemical stain with haematoxylin counterstain for bcl-2, ×40). ...

On the basis on a novel metformin assay, Frid et al. published clinical recommendations on use of the drug in patients with type 2 diabetes and varying severity of chronic kidney disease (CKD). The researchers stated that a threshold of 20 μmol/L (2.8 mg/L) was a ‘preliminary upper therapeutic limit’ [1]. However, the latter work can be questioned for several reasons: (i) the patients with an estimated glomerular filtration rate (eGFR) >60 mL/min/1.73m2 were not given the full therapeutic dose (median: 1500 mg/day); (ii) 22% of the patient population had an eGFR

The nephrology teaching legacy is extensive. Claude Bernard, Carl Ludwig, Homer Smith, William Schwartz, Arnold Relman, Karl Gottschalk, Robert Narins, Jerome Kassirer, Mitchell Halperin and many others made their mark in the area of teaching the internal environment and its regulation, a discipline commonly termed ‘fluid and electrolytes’. Other medical specialties need these skills every day: critical care medicine, anaesthesiology, surgery, paediatrics and many others. However, the duty of teaching this material to medical students and house staff physicians is the purview of nephrologists. Thus, when other doctors cannot come to grips with these problems, we should become introspective and blame ourselves. We must insist that more time be devoted in medical school to house staff training, board examination preparation for medical specialties other than our own and to continuing medical education to pass this information on to younger colleagues. A recent patient underscored the lack of skills inherent in our own university house staff training programme in this regard.

A 26-year-old female patient was introduced to our lipid consultations for further diagnosis and treatment. She had two strokes, occurring at the age of 19 and 24, respectively. In addition, she was suffering from spastic tetraparesis as a consequence of perinatal asphyxia. Because of her history of strokes, a blood coagulation factor analysis was performed. Here, the following blood coagulation disorders were identified: von Willebrand disease type 1, protein S deficiency and increased levels of lipoprotein a (Lp(a)). In sum, these indicate a significantly increased risk of thrombophilia. Recent research has shown two single-nucleotide polymorphisms in the LPA locus (6q26–27) to be strongly associated with increased Lp(a) levels as well as increased risks of coronary heart disease and stroke [1, 2]. A common genetic variant of LPA (rs10455872) was identified in the patient corresponding to her significantly increased Lp(a) levels. Due to the patient's high-risk thrombophilia and taking into account considerably narrowed coronary vessels with a high risk of a cardiovascular event as determined by cardiac MRI, weekly lipoprotein apheresis treatment (LA) was initiated. Furthermore the patient was found to have a positive family anamnesis for different forms of thrombophilia (Table 1). Table 1. Family history for different thrombophilia disorders Prior to the start of LA, the patient had been pregnant twice, but lost the fetus in the 6th and 9th gestation week, respectively, while exhibiting high levels of Lp(a) of around 200 mg/dL (480 nmol/L). It is known that Lp(a) levels may rise during pregnancy [3]. No further examination of the placenta had been carried out in the context of these miscarriages. While receiving weekly LA the patient got pregnant again, but lost the fetus in the 14th gestation week. At the time, the recorded Lp(a) levels varied between 190 mg/dL (456 nmol/L) at the start and 56 mg/dL (134 nmol/L) at the end of an average apheresis procedure. A now conducted histopathological examination of the placenta revealed a fulminant microcirculatory perfusion disorder caused by multiple microthromboli. The patient got pregnant again for the 4th time. Due to this course of events the therapy was intensified by doubling the LA rate to biweekly treatment. Here, thermofiltration (Diamed®; Koln; Germany), using a plasma volume of 4000 mL per treatment, was selected. This regimen allowed the decrease of LDL and Lp(a)-cholesterol levels by >75% when compared with the start of the apheresis treatment. Following LA procedures, Lp(a) was measured within the normal range [25 mg/dL (60 nmol/L)]. Regular thrombophilia screenings were made to regulate the administration of high-dose coagulation factors [von Willebrand factor: ristocetin cofactor (VWF:RCo), factor VIII and factor XIII]. The patient got pregnant again. The pregnancy progressed normally and without complications. Due to the increasing risk of thrombosis, we decided to perform a premature delivery by Caesarean section in the 34th week of pregnancy. A thrombophilia screening of the umbilical cord blood could not be evaluated as of yet. Even though coagulation factors were administered as necessary the patient suffered from smaller bleedings without clinical relevance in the area of the surgical wound. The newborn girl developed well and was able to leave the incubator on Day 14 after the delivery. Up until now, no further clinically significant events have been reported for either the patient or the child. This case illustrates how strong the association of thrombophilia [4] and increased Lp(a) levels [5] can be with regard to miscarriages. Only a high-rate extracorporeal Lp(a) elimination by LA and regular screening and substitution of coagulation factors allowed a pregnancy to be brought a successful end. Furthermore the importance of a well-coordinated interdisciplinary, patient-centred approach to the management of high-risk pregnancy is demonstrated. Whether the therapeutic strategy successfully employed here is transferable to other cases of patients with high-risk thrombophilia who desire children has to be investigated in future studies. Again, this clinical case suggests that Lp(a) is not only relevant to the known artherosclerotic processes (apoplexy of the patient) but seems to play an active role in the coagulation system, further increasing the risk of thrombophilia (in the placenta) as well.

Malaria is a mosquito-borne infection caused by parasites of the genus Plasmodium and may present as a spectrum of diseases ranging from asymptomatic infection to death. The estimated 660 000 fatal cases annually are almost all caused by Plasmodium falciparum, due to the ability of this species to cause high parasitaemia and sequestration of the infected erythrocytes in the microvasculature of vital organs. P. falciparum is also the cause of the vast majority of cases of renal failure in malaria. The incidence of acute kidney injury (AKI) in P. falciparum is ∼1–5% in natives of endemic areas who have some degree of immunity, but is much higher in non-immune subjects, with reported incidences of up to 30% [1]. When AKI occurs, mortality is high and ranges from 15 to 45%. The World Health Organization therefore classifies malaria infection with AKI as severe malaria. We describe a patient with severe P. falciparum infection and AKI, in which renal biopsy revealed an unexpected cause.