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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

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.

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.

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).

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

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.

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.

The incidence of clinically significant thrombosis in a cancer patient varies from 5 to 60%. Venous thrombosis remains more common than arterial thrombosis, and combined arterial and venous thrombosis in cancer patients is rare [1]. We report a rare case of combined pulmonary thromboembolism and complete thrombotic occlusion of the renal artery in a patient with non-small cell lung cancer (NSCLC) while receiving chemotherapy.

Granulomatosis with polyangiitis (GPA, formerly known as Wegener's granulomatosis) is a rare necrotizing vasculitis of small and medium-sized blood vessels known to cause inflammation of the respiratory tract (e.g. rhinitis, pulmonary capillaritis) and kidney disease (ranging from microhematuria to rapidly progressive glomerulonephritis) [1]. More than 75% of patients with GPA eventually develop renal involvement which can progress to end-stage renal disease. The classic renal biopsy finding is pauci-immune crescentic or segmental necrotizing glomerulonephritis [1]. We report here a 14-year-old male who presented with a 3-week history of sinusitis, arthralgias, epistaxis, conjunctivitis and a petechial rash over his lower extremities. His laboratory workup was significant for high titer cytoplasmic anti-neutrophil cytoplasmic antibodies (c-ANCA) at 1:640; however, anti-proteinase 3 (PR3) and anti-myeloperoxidase (MPO) antibodies were initially negative. Serologic testing also revealed an elevated ESR at 35 mm/h (35 mm/h), elevated CRP at 52.4 nmol/L (5.5 mg/L), and an elevated rheumatoid factor at 36 kIU/L (36 IU/mL). His initial serum creatinine was 61.88 µmol/L (0.7 mg/dL), and his urinalysis showed hematuria with no leukocyturia and no proteinuria (random urine protein/to/creatinine ratio was 0.14). Plasma protein and serum albumin were normal at 77 g/L (7.7 g/dL) and 41 g/L (4.1 g/dL), respectively. He had a pulmonary nodule and right maxillary sinus opacification revealed by radiography. The patient was diagnosed with GPA without significant renal involvement and was started on daily prednisone (0.5 mg/kg/day) and weekly methotrexate (15 mg/m2/week). Monthly cyclophosphamide infusions (750 mg/m2 per dose) were initiated soon after due to the severity of the symptoms. Despite 3 months of therapy, however, the patient suffered from worsening arthritis, fatigue, cough, rash and elevation in CRP to 187.6 nmol/L (19.7 mg/L). His prednisone dose was subsequently increased to 1 mg/kg/day. Six months after the onset of symptoms, anti-PR3 antibodies were positive. Concern grew for poor response to the standard therapy given the persistent symptoms and worsening serology despite treatment with steroids, methotrexate and cyclophosphamide for more than a year. Fifteen months after the onset of symptoms, and 1 year after the initiation of therapy, the patient experienced an 8 kg weight loss, fatigue, continued epistaxis and sinusitis, and development of nephrotic-range proteinuria (3400 mg/day). Serum albumin remained normal at 44 g/L (4.4 g/dL). The serum creatinine mildly increased from 53 µmol/L (0.6 mg/dL) to 70.7 µmol/L (0.8 mg/dL). A kidney biopsy was performed. Light microscopy revealed 16 glomeruli, with 5 showing segmental sclerosis; 3, global sclerosis; and 1, fibrous crescent (Figure 1A). Immunofluorescence (IF) showed comma-shaped C1q and trace granular IgG deposits in the glomeruli, as well as C3 deposition in the blood vessels (Figure 1B). Electron microscopy (EM) demonstrated focal foot process effacement as well as focal subendothelial and paramesangial electron dense deposits. Based on these biopsy findings, the patient was diagnosed with C1q nephropathy (C1qN). Given the lack of clinical response to the original therapy, prednisone, methotrexate and cyclophosphamide were discontinued and tacrolimus was started at 1 mg twice daily. Plasmapheresis and rituximab were considered as therapeutic options; however, due to the patient's good response to tacrolimus, these treatments were not performed. A month later, lisinopril was initiated to treat the patient's hypertension. Fig. 1. Renal histological findings and response to treatment with tacrolimus and lisinopril. (A) Light microscopy shows focal segmental and global glomerulosclerosis along with varying degrees of interstitial inflammatory infiltrate and fibrosis. Arrow points ... The patient has been followed for 2 years since diagnosis. After initiation of tacrolimus, an improvement in his pulmonary, musculoskeletal and ophthalmic symptoms was observed. His proteinuria decreased from a peak of 3389 to 598 mg/day (Figure 1C); the c-ANCA titer decreased from a peak of 1:640 to 1:320; and the anti-PR3 antibody titer decreased from a peak of 72 to 62 units. C1qN was originally defined by Jeanette and Hipp as a disease process characterized by nephrotic-range proteinuria, with kidney biopsy findings demonstrating dominant C1q staining in a predominantly mesangial pattern on IF [2]. The glomeruli may show minimal abnormalities, focal segmental glomerulosclerosis or mesangial proliferation. Widespread effacement of the podocyte foot processes can also be seen on EM. Exclusion criteria for C1qN include evidence of systemic lupus erythematosus, IgA nephropathy or membranoproliferative glomerulonephritis type I [2]. Clinical manifestations can range from relatively benign cases of isolated hematuria or proteinuria to severe cases of nephrotic syndrome, nephritic syndrome or a combination of the two [2]. Very few cases of ANCA-associated vasculitis with C1qN have been reported to date [3, 4], and to our knowledge, C1qN has not been reported specifically in association with anti-PR3-positive GPA. In our patient, we postulate that B-cell activation may have resulted in glomerular immunoglobulin deposition, allowing for binding of C1q to the Fc portion of the IgG antibodies. This case may also represent two concurrent rare diseases in one individual without a causal relationship. Since the overall pathogenesis of C1qN remains incompletely understood, the exact mechanism by which the patient developed C1qN in the background of GPA remains unknown. According to recent case series reports, most patients with C1qN and steroid-resistant nephrotic syndrome achieved remission with the addition of a calcineurin inhibitor, e.g. cyclosporine or tacrolimus [5]. We hypothesize that in our patient with GPA and C1qN resistant to conventional therapy, treatment with tacrolimus resulted in systemic immunomodulation leading to a decrease in the intensity of the symptoms of systemic autoimmune disease, as well as reduction of proteinuria. Lisinopril likely further assisted in the resolution of proteinuria. This is the first case to our knowledge of a patient with C1qN associated with GPA, who demonstrated dramatic improvement of his nephrotic-range proteinuria and extra-renal symptoms with tacrolimus. While this represents a rare case of C1qN in the setting of GPA, consideration should be given to this entity in patients with refractory GPA and proteinuria, as these manifestations could portend a worse prognosis. Moreover, this report suggests that tacrolimus could be considered as a therapeutic option in such cases.

Take home message Sporting events in the most extreme of places and conditions can safely take place provided adequate medical facilities and resources are available, along with adequate education of the participants. The Everest marathon is a biannual race run from 5184 m near Everest base camp and finishing in the Sherpa capital of Namche Bazaar at 3446 m. It is recognised as the highest and possibly the toughest marathon race in the world. The runners start at a height at which the atmospheric pressure and inspired oxygen pressure are 50% of the value at sea level.1 It began in 1987 to an outcry from many altitude experts who felt the risks of running at that altitude were unjustifiable.2 However, it has proven to be a safe if tough race. There have been no fatalities. On average over the seven marathons, 5–10% of contestants have been unable to complete the whole race, some completing part of the course.3 In 1995 the course was unsafe because of a heavy snowfall, and only a half marathon was run. The previous races have been held in late November after the monsoon season. This year for the first time it was held in April, a warmer time of year. Daytime temperatures were typically around freezing, falling at night to −10°C. The main medical problems facing previous medical teams have been altitude sickness, diarrhoea and vomiting, chest infections, and musculoskeletal disorders, especially anterior knee pains, contusions, and blistering of the feet.4 Knowledge of previous problems and the use of drug formularies from previous marathons helped to ensure that the expedition was adequately equipped. This isolated route is away from medical access for long parts of the trek, requiring the medical team to be completely self sufficient. The race has potential for …

Atypical haemolytic-uraemic syndrome (aHUS) is a disease of uncontrolled complement alternative pathway activation. Eculizumab induces terminal complement blockade (TCB), and is safe and effective for aHUS treatment as evidenced by its recent approval by the US Food and Drug Administration and the European Commission. A 26-year-old woman was admitted 1 week after her first childbirth for aHUS with creatinine 6.2 mg/dL (550 µmol/L), haemoglobin 3.6 g/dL (36 g/L), lactate dehydrogenase 2155 U/L (upper normal limit 248), 9% schizocytes and platelet count 49 × 103/µL (49 × 109/L). She had a medical history of Crohn's disease 5 years earlier and a skin melanoma 3 years earlier. Family history was remarkable with her father's brother presenting two renal graft losses related to aHUS despite plasma exchange (PE). The patient and her uncle both carried combined heterozygous mutations in genes coding for Factor H (p.Lys1186Thr) and Factor I (p.Ile322Thr). Daily PE was started with 60 mL/kg fresh frozen plasma substitution for 80 kg body weight with an initial positive haematological response without improvement of renal function requiring haemodialysis. Due to family history and suspected genetic background that was confirmed later, the patient was switched to eculizumab [1–3], 900 mg on Day 3 post-admission (PA). Placental retention was subsequently diagnosed and treated but a second 900 mg eculizumab infusion 10 days-PA was not effective in controlling aHUS (decreasing platelet count). Daily PE was re-started without supplemental eculizumab. During eculizumab treatment, complement activity measured with a validated sensitized sheep erythrocytes lysis assay (CH50) is expected to be

A 43-year-old woman with a history of psoriasis vulgaris was admitted for nephrotic syndrome that had started 6 months before. Renal biopsy revealed membranous glomerulonephritis (MGN). She did not receive any therapy for MGN. Two months later she started therapy for psoriasis with adalimumab, which resulted in disappearance of psoriatic skin lesions with progressive reduction of 24-h proteinuria. This is the first report of therapeutic efficacy of adalimumab in MGN. Idiopathic membranous glomerulonephritis (MGN) is the most common cause of nephrotic syndrome in adults. It is considered an autoimmune disorder in which antibodies against some antigens result in generation of immune complex with subsequent activation of the complement cascade [1]. Recently, the M-type phospholipase A2 receptor (PLA2R), expressed in podocytes, has been identified as the autoantigen [2]. Psoriasis is an immune-mediated chronic inflammatory skin disease with a strong genetic background. Chronic glomerulonephritis associated with psoriasis vulgaris has been reported in the literature [3]. However, because of the limited number of cases and the lack of specific histological findings, the pathogenetic mechanisms of these associations remain unclear [4].

Sir, Following the study of effects of endurance training on proteinuria and hematuria in untrained young females [1], we conducted an investigation surrounding the effects of resistive training (RT) on proteinuria and hematuria in 36 trained (regular practice during prior 2 years) healthy women. They aged 20–25 years (22.19 ± 1.81) with body mass index of 21.8 ± 1.51 kg/m2 and VO2max of 38.4 ± 1.54 mL/kg/min. The participants were randomly assigned into Group A (intermittent RT), Group B (continuous RT) and control Group C (each, n = 12). Two days before the RT program, the participants of Groups A and B met in a training session with the intensity of 20% of one-repetition maximum (1RM), while urine samples were obtained at pre-training1 and post-training1 (0 and 1 h) stages. A1RM is the maximum weight that can be lifted one time with proper technique, which was calculated for each movement in each trainee. The participants performed the training protocol (3 days/week) during 8 weeks with an increasing intensity rate of 5% of 1RM per week from 20 to 55%. Each session consisted of two circuits including seven 2.5-min movements consisting attempts against compression on different organs (breast, arm and foot) and lateral traction. There were 2- and 1-min resting intervals between two circuits and two movements, respectively. Indeed, the total time for each session was 65 min which included: a 10-min light warming up, RT protocol for 47 min and a cool-down exercise for 5–10 min. Group B performed each movement with a constant speed (V = one attempt per 2.5 s), continuously. Group A was asked to do each movement with different speed (2V for 10 and ½V for 20 s), intermittently. The speed of movements was controlled by a metronome. Two days after termination of training workouts, following an effort of 20% of 1RM, similar urine samples were collected as pre-training2 and post-training2 stages. Table 1 shows urinary protein levels at different stages. Table 1 Urinary protein levels of participants at different stagesa A significant increase in all urinary protein levels (mixed type, predominantly albuminuria) was observed compared to basal levels, particularly following RT program (P = 0.02, 0.001 and 0.002 for total protein, albumin and β2 microglobulin, respectively), without any significant difference between the two experimental groups (all P > 0.05). No microscopic hematuria was detected in urine samples (all in luteal phase). It seems that different types of physical training (resistive, endurance, continuous or intermittent) have no preference each other in urinary protein loss [1], however, some studies oppose this finding [2]. In addition, physical training may have a protective effect against exercise-induced hematuria in untrained and trained females. Undoubtedly, further researches regarding this issue are needed.

A five-year-old boy presented (Day 0) with gingival bleeding and pancytopenia (white blood cells: 1.7 × 109/L; hemoglobin: 7.3 g/dL; platelets: 16 × 109/L). A coagulation panel was unremarkable. Peripheral blood smear revealed dysmorphic promyelocytes with red-blue granules, folded reniform nuclei and no Auer rods. Bone marrow examination showed immature myeloid cells (>60% promyelocytes) that were positive for myeloperoxidase (MPO), CD117, CD13 and CD33, and negative for CD34 and HLA-DR. Cytogenetic analysis showed a male karyotype with 46,XY, t(15;17)(q24;q21). Quantitative real-time polymerase chain reaction was positive for PML-RARα. A diagnosis of acute promyelocytic leukemia (APL) was established. Induction chemotherapy with daunorubicin (50 mg/m2 Days 1, 3 and 5), cytarabine (100 mg/m2 every 12 h, Days 1–10) and thioguanine (100 mg/m2 every 12 h, Days 1–10) along with all-trans retinoic acid (ATRA; 45 mg/m2 per day in two divided doses starting on Day 1) was initiated on admission Day 2. Prophylactic dexamethasone (0.1 mg/kg twice daily) was administered along with ATRA. On Day 9, the patient developed a hypertensive crisis, bilateral lower extremity edema, proteinuria (24-h urine protein 1000 mg) and hyperlipidemia (triglycerides: 525 mg/dL, total cholesterol: 275 mg/dL). His serum albumin at this time was 3.2 g/dL. Given the above presentation and the definition of nephrotic-range proteinuria in children (>40 mg/m2/h), a diagnosis of nephrotic syndrome (NS) (most likely minimal change disease) was established and steroids (prednisone 2 mg/kg/day) were initiated. Proteinuria and other manifestations of NS resolved on admission Day 26, after which steroids were quickly tapered and eventually discontinued. The patient has now completed the second course of DAT without signs or symptoms of NS. During the second course, he only received prophylactic doses of steroids. The association of NS with acute myeloid leukemia (AML) is rare, with only 10 cases reported previously (Table 1). There was a remarkable male predominance (80%), and the median age at diagnosis was 33 (range: 3–81) years. Surprisingly, 45% of all cases and all three pediatric cases were APL. NS was present before treatment in 45% of cases, suggesting a direct pathogenic role of leukemia. In other cases, anthracycline therapy was the main culprit. Histopathological findings on renal biopsy did not reveal a unique pattern and varied from minimal change disease (MCD) to focal segmental glomerulosclerosis (FSGS), immune complex deposition, macrophage infiltration, membranous glomerulonephritis, proliferative glomerulonephritis and detachment of epithelial cells from the glomerular basement membrane. From the nine patients who received some form of treatment for NS, steroids were the chosen treatment in seven patients, with a response rate of 86%; the other two patients were treated only with chemotherapy and NS responded to treatment in both. Table 1. Summary of previous reports on the association between AML and NS A number of mechanisms may explain the rare association between NS and AML. Disruption of podocyte integrity and function due to cytokine release has been proposed as a mechanism of nephrotic syndrome during ATRA-induced differentiation syndrome in APL [1]. A causal relationship between NS and AML is further supported by the response of proteinuria to chemotherapy for AML and the association between higher leukemia burden and more proteinuria [1, 2]. Anthracyclines have been proposed as a culprit in the development of NS following treatment of AML since they can cause acute renal tubulointerstitial toxicity [3, 4]. Also, adriamycin rapidly increases the expression of the ligands on podocytes for advanced glycation end products, leading to podocyte stress and glomerulosclerosis in mouse models [5]. Adriamycin is now often used to induce experimental FSGS [6, 7]. Finally, NS in AML may reflect a local immune complex-mediated process [8, 9]. Given the absence of proteinuria before AML treatment in our patient, we believe daunorubicin was the most likely cause of NS in the present case. However, a direct effect of ATRA (e.g. terminal differentiation of promyelocytes and toxic effects of the released granules) cannot be ruled out. He had no signs of recurrent NS after re-exposure to chemotherapy, suggesting re-challenge may be safe in drug-induced NS.

The concomitant presentation of tubulointerstitial nephritis and uveitis is known as tubulointerstitial nephritis and uveitis (TINU) syndrome, also known as the Dobrin syndrome. Since first described in 1975

Tumor lysis syndrome (TLS) is a group of metabolic abnormalities that are usually seen in cancer patients treated with chemotherapy although it can occasionally occur spontaneously without chemotherapy in patients with a high tumor burden. It is due to the rapid lysis of tumor cells resulting in the release of large amounts of intracellular contents in the blood stream. This results in the rapid development of high levels of phosphate, potassium and uric acid accompanied by a profound decrease in serum calcium. TLS usually occurs in bulky tumors with a high turnover such as leukemias and lymphomas. The malignancy can be undiagnosed at the time of development of TLS [1]. In this report we present a case in which the patient presented with spontaneous TLS (STLS) and was later diagnosed with high-grade B-cell non-Hodgkin's lymphoma (NHL).

Orthostatic proteinuria is characterized by elevated levels of urinary protein excretion while in the upright or lordotic position and normal excretion when in the supine or recumbent position, such as that during bed rest. This type of proteinuria is the most frequent cause of isolated proteinuria in children and adolescents. In adolescents, the prevalence of orthostatic proteinuria is reported to be between 2 and 5% [1]. However, it is an uncommon disorder in individuals over 30 years of age [2]. As it is a benign condition requiring no further evaluation or specific therapy, the differential diagnosis of orthostatic proteinuria is crucial in clinical practice to avoid unnecessary interventions such as a kidney biopsy.

IgA nephropathy is the most common cause of idiopathic glomerulonephritis in the developed world. Although this disorder was initially thought to follow a benign course, it is now recognized that slow progression to end-stage renal disease occurs in up to 50% of affected patients. The two major clinical presentations of IgA nephropathy are gross hematuria and persistent asymptomatic microscopic hematuria with or without mild to moderate proteinuria, which can also be seen in nutcracker syndrome caused by nutcracker phenomenon. The nutcracker phenomenon refers to the compression of the left renal vein between the abdominal aorta and the superior mesenteric artery with impaired blood outflow accompanied by distention of the distal portion of the vein. Nutcracker syndrome is the clinical manifestation of nutcracker phenomenon characterized by a wide spectrum of symptoms, such as hematuria, orthostatic proteinuria, pain or gonadal vein syndrome, and varicoceles.

Cystic fibrosis (CF) is the most common autosomal-recessive condition affecting the white population, with an incidence ranging between 1:2500 and 1:1800 births. It is caused by a mutation in the CFTR gene, encoding the polyprotein CF transmembrane conductance regulator (CFTR), which functions as an ATP-responsive chloride channel in the apical membrane of epithelial cells. Pathologic changes related to CFTR mutations mostly affect secretory cells, resulting in low secretion volume and increased viscosity and promoting mucosal obstruction in the lung, pancreas, biliary tract, sinuses and reproductive tract [1]. Patients with CF currently show a continuing improvement in their life expectancy, an improvement that allows for better multidisciplinary monitoring and earlier therapeutic interventions. Owing to their longer life expectancy, CF patients present complications that were not recorded before [2]. This is illustrated by the following report of two cases of renal AA amyloidosis in women with CF.

Hidradenitis suppurativa (HS), also known as Verneuil's disease [1] or acne inversa, is characterized by hyperkeratosis of the follicular epithelium, resulting in obstruction of the follicular stoma and chronic perifollicular inflammation with remissions and relapses, usually involving skin overlying the axillary, inguinal, perianal, perineal and inframammarian regions. It usually presents in the second and third decades of life, has a female preponderance, no racial predilection and a prevalence of 4%. Some causing factors might be obesity and related hormonal changes, hyperandrogenism, immunologic and genetic status, diet and smoking [2]. The diagnosis is based on the presence of relapsing lesions in typical anatomical regions. HS may be localized with chronic, relapsing, superficial papulopustular lesions, as it may be associated with deep, widespread abscesses, sinus tracts, fistulas, malignancies like squamous cell carcinoma and systemic complications like arthropathy or anaemia [3]. Besides topical and surgical care, therapy with antibiotics, steroids, retinoids and anti-TNF agents is usually considered. Rarely, amyloidosis may complicate the cutaneous disease [4]. A 42-year-old male was referred to our hospital for nephrotic syndrome. Three years before he was diagnosed with hidradenitis suppurativa when papulopustular lesions over the inguinal, perineal, perianal and axillary regions appeared. Over these 3 years, he had relapses with fever, extensive perineal tenderness and partial remissions leaving fibrotic scar tissue following treatment with topical steroids, keratolytics and antibiotics. His temperature was 37.1°C, blood pressure 140/90 mmHg and heart rate 76/min. He had bilateral pretibial pitting oedema and active bilateral inguinal, perineal, perianal and left axillary papulonodular and pustular, hyperaemic, tender lesions of 2–3 cm diameter, some of which fluctuating and draining, scar tissue, sinus tracts of the older lesions and bilateral inguinal and left axillary tender lymphadenopathies, the largest of which being 2 cm in diameter (Figure 1). Fig. 1. Left axillary active lesion (a) and sinus opening on the right lateral scrotal wall (b). No pathogen was isolated in the cultures of sinus openings and in his blood. Topical keratolytic and anti-inflammatory drugs combined with roxithromycin, rifampicin and clindamycin treatment for 1 month resulted in partial remission of the active lesions. A biopsy of the perineal skin revealed a non-specific inflammatory reaction without amyloid deposition. He was found to have a heterozygous M680I mutation of the exon 10 of the MEFV gene. Kidney biopsy revealed glomerular, perivascular and interstitial deposits that stained with Gentian violet, compatible with amyloidosis that was identified immunohistochemically as AA amyloidosis (Figure 2). Despite treatment with colchicine, kidney failure and proteinuria showed progression. Fig. 2. Interstitial eosinophilic amorphous amyloid deposition on haematoxylin and eosin stained section (a), strong positive glomerular and perivascular staining with amyloid A (b) and P component positivity (c). Amyloidosis and nephrotic syndrome are rare complications of HS with only four such cases in the literature [4]. One had rectal biopsy-proven symptomatic gastrointestinal amyloidosis, another one had infiltrative cardiomyopathy, assumed to be caused by amyloidosis. In our case, there was no amyloid deposition in skin biopsy and the abdominal computed tomography scan was normal with no hepatosplenomegaly. The patient did not have diarrhoea or gastrointestinal bleeding. His echocardiography was normal and he had no neuropathy. Although seen prevalently in endemic regions, carriers of MEFV gene mutations may have an increased risk of inflammatory diseases resulting in amyloidosis. The clinical course of inflammatory diseases like rheumatoid arthritis may be more severe in MEFV gene mutation carriers [5]. Despite its benign nature, hidrosadenitis must be early and actively treated as any chronic suppuration to avoid the development of AA amyloidosis, especially in carriers of the MEFV gene mutation.

Rothia mucilaginosa is a Gram-positive, coagulase-negative, encapsulated, non-spore-forming coccus considered part of the normal flora of the upper airway in humans. It is considered to have low virulence, but has been reported to cause infections in various organs in immunocompromised patients. Only two cases of R. mucilaginosa peritonitis in chronic peritoneal dialysis (PD) patients have been reported previously, and we report the third case here in a patient with human immunodeficiency virus, who was successfully treated with intraperitoneal vancomycin.

The most frequent complications that occur after the completion of an internal arteriovenous fistula are thrombotic. Other complications, such as infection, cardiac decompensation, aneurysm/pseudoaneurysm or median nerve injury, are less common. Nonetheless, after transplantation, adjuvant immunosuppression has long-term side effects, such as the development of malignancies. Here, we report the case of a patient subjected to renal transplantation who developed an angiosarcoma located in an internal arteriovenous fistula.

A 75-year-old male was admitted for investigation of acute kidney injury. His medical history was significant for hypothyroidism and transfusion-dependent myelodysplastic syndrome. A bone marrow biopsy 1 month prior to admission had categorized him as having refractory anaemia with excess blasts (RAEB) Stage-II. His medications included thyroxine, cholecalciferol and the cytotoxic agent azacitadine. Over the preceding 6 months, he had noticed progressive lethargy, loss of weight and functional decline. Examination was unremarkable. Biochemistry demonstrated a serum creatinine level of 350 µmol/L, which had markedly worsened over 2 months. This was associated with 1.06 g/day proteinuria but no haematuria. Haematology showed normocytic anaemia (Hb 70 g/L), thrombocytopaenia (Plt 48 × 109/L) and marked leucocytosis (WCC 38.8 × 109/L). Dysplastic changes and occasional blasts were noted on the blood film (Figure 1). Serum protein electrophoresis, uric acid, autoimmune studies, hepatitis and HIV serology were unremarkable. Ultrasound demonstrated normal-sized kidneys of normal echogenicity and no evidence of obstruction. Fig. 1. May–Grunwald–Giemsa staining of the peripheral blood film shows pleomorphic population of blasts with an open chromatin and high nuclear:cytoplasmic ratio (thick arrows). Dysplastic neutrophils are also noted with abnormal segmentation ... A renal biopsy was performed, which showed renal cortex with heavy infiltration of atypical cells within the interstitium and lumina of small vessels. These cells had irregular nuclear membranes, prominent nucleoli and granular cytoplasm, and showed positive immunoperoxidase staining with myeloperoxidase, confirming the diagnosis of acute myeloid leukaemia (AML) with renal infiltration (Figures 2 and ​and33). Fig. 2. Highly cellular infiltration in the renal interstitium, atypical myeloid blasts with irregular nuclear membranes, prominent nucleoli and granular basophilic cytoplasm (H&E ×200). Fig. 3. Positive immunohistochemical staining for myeloperoxidase (MPO IHC ×100). A repeat bone marrow biopsy was subsequently performed which showed transformation into AML. The cause of the progressive kidney dysfunction was thus attributed to renal infiltration from AML. In view of the patient's poor prognosis and functional state, community-based palliative care was instituted. He passed away several weeks later. Malignant infiltration of the kidneys as a cause of renal failure has been well described [1–3]. The commonest causes are low-grade non-Hodgkin's lymphoma and acute lymphocytic leukaemia [4]. AKI due to diffuse kidney infiltration from AML has been reported in the setting of other precipitants [5]. Our case is unique, in that it demonstrates acute kidney injury resulting directly from malignant infiltration of renal parenchyma from AML. Conflict of interest statement. None declared.

Hereditary haemorrhagic telangiectasia (HHT), or Osler–Weber–Rendu syndrome, is inherited in an autosomal-dominant fashion. There are two different forms of HHT: HHT type 1, caused by mutations in the endoglin gene, located in chromosome 9 (which encodes endoglin), and HHT type 2, caused by mutations in the gene encoding activin A receptor type II-like 1 (ALK1) on chromosome 12. Mucocutaneous telangiectasias, arteriovenous malformations, epistaxis, gastrointestinal bleeding and iron-deficiency anaemia are the commonest clinical manifestations of HHT [1]. Hepatic involvement, characterized by different arteriovenous malformations within the liver parenchyma, occurs in up to 74% of patients with HHT [2]. As far as we know, no information has been published on therapeutic alternatives for haemodialysis patients suffering from severe complications of HHT. We report on a 59-year-old woman with chronic renal failure secondary to bilateral renal hypoplasia and undergoing haemodialysis, who received the diagnosis of HHT. She had presented relapsing epistaxis during the last year, with severe anaemia and hypotension. Due to the need for weekly transfusions and the poor tolerance to haemodialysis sessions, we consider treatment with raloxifene (60 mg/day), a selective estradiol receptor modulator. Raloxifene increases the expression of endoglin and ALK1, whose synthesis is defective in HHT patients, at the surface of endothelial cells [3]. A remarkable improvement of HHT symptoms along with a significant decrease in the number and severity of epistaxis was observed after raloxifene treatment. However, 6 months after the onset of raloxifene treatment, the patient presented with signs and symptoms of high-output cardiac failure, with severe ascites and a left pleural effusion. Increase of haemodialysis ultrafiltration along with large-volume paracentesis were started, but the patient showed a poor tolerance to these measures, owing to the presence of anaemia, hypotension and chronic liver disease. Serum biochemistry demonstrated a progressive cholestasis. A computed tomography (CT) scan showed liver cirrhosis with splenomegaly and massive arteriovenous malformations (Figure 1). Prompted by the progressive clinical deterioration of the patient, we decided to start treatment with bevacizumab, a humanized recombinant monoclonal antibody against the vascular endothelial growth factor (VEFG). The VEGF is a key regulator of angiogenesis and is upregulated in a variety of diseases. On the other hand, endoglin and ALK1 are involved in the transforming growth factor-β signalling pathway, which is a potent stimulator of VEFG production. Bevacizumab has been shown to be effective in diseases of abnormal angiogenesis, improving survival and symptomatology [4, 5]. Bevacizumab has been also used for the treatment of liver complications of HHT, inducing a clear improvement [6]. After obtaining the patient's informed consent, six courses of bevacizumab (5 mg/kg) were administered during a 3-month period and raloxifene was maintained without changes. A further reduction in the frequency of epistaxis was observed besides a remarkable improvement of ascites and liver enzymes. As shown in Figure 1, serial CT scans demonstrated a clear diminution of hepatic vascularity and a smooth contour of the liver. Fig. 1. CT scan of the liver with intravenous contrast before and 6 months after bevacizumab treatment, showing a dramatic reduction of vascularity and improvement of liver surface. Many different therapies have been proposed for epistaxis and hepatic involvement in HHT, but none of them have shown conclusive results. Hormonal therapy with estradiol for epistaxis and gastrointestinal management of HHT has shown a variable degree of efficacy depending on the patient. According to our experience, both raloxifene and bevacizumab are very effective alternatives for the treatment of severe HHT in haemodialysis patients.

Sir, Collapsing glomerulopathy (CG) represents a distinct pattern of renal response to injury characterized by segmental to global collapse of capillaries in association with hyperplasia and hypertrophy of the visceral epithelial cells (VECs) associated with marked tubulointerstitial damage [1]. The reporting of CG in the literature has increased with the growing awareness among the nephrologists and pathologists of its association with disorders other than human immunodeficiency virus-1 infection [1–3]. Currently, it is classified as a variant of focal segmental glomerulosclerosis (FSGS) [3]. However, more recently, some authors have suggested that this relationship with FSGS may not last longer, and sooner or later it may be classified as a separate nosologic entity [2, 3]. With increasing awareness, the vascular lesions and thromboembolic phenomenon with consequent ischaemia have also emerged as important etiopathogenetic mechanisms in the development of CG in both the native and the transplanted kidneys [4–7]. More recently, the direct causal relationship between patchy infarction and de novo CG in transplanted kidneys has been reported [8]. However, no such link with acute cortical necrosis (ACN) secondary to post-partum haemorrhage (PPH) and hypovolaemic shock in native kidneys of young patients with no vasculopathy has been reported till date. We herein report two cases of CG involving the glomeruli in the vicinity of patchy ACN found on biopsies from native kidneys in two patients. Both patients were young females, 17 and 26 years, respectively, and presented with acute renal failure (ARF) following PPH. No history of drug intake or past medical illness of note was elicited. Ultrasound findings were not typical of ACN. Urine analysis was non-contributory. Relevant viral and autoimmune serology was negative. Both patients required dialysis initially, but one is off dialysis and maintaining serum creatinine at 221 μmol/L 8 months post-biopsy, whereas the other is on haemodialysis, waiting for kidney transplantation 10 months after diagnosis. Renal biopsies in both cases showed patchy infarction. In addition, both biopsies showed variable numbers of glomeruli in the vicinity of infarction, with segmental to global collapse of capillaries associated with hyperplasia and hypertrophy of VECs (Figure 1). There was moderate mixed inflammatory cell infiltration in the interstitium. However, no vasculopathy or thrombotic lesions were noted. Immunofluorescence was performed on snap-frozen tissue and showed segmental positivity of immunoglobulin M (IgM) and C3 in areas of collapsed tufts of viable glomeruli, whereas IgG, IgA and C1q were negative. Thus, both cases showed typical glomerular changes of CG involving the glomeruli in close proximity to patchy ACN. Fig. 1. High-power view showing a glomerulus from one of the renal biopsy specimens showing global collapse of capillary tufts associated with marked hypertrophy and hyperplasia of the podocytes. These show marked cytoplasmic vacuolization and protein resorption ... A report of three cases of zonal distribution of CG in the vicinity of patchy infarction secondary to severed accessory renal vessels in the transplanted kidneys has recently been published [8]. Similarly, occasional reports are also available in the literature, in which an association of FSGS and CG in the native kidneys with the vascular lesions has been observed [4–6]. However, this is the first report of CG in association with ischaemic ACN secondary to hypovolaemia resulting from PPH in native kidneys in two young females and provides evidence for the broad etiopathogenetic pathways leading to the final common pattern of CG. We also believe that this lesion is of secondary or reactive nature, rather than primary or idiopathic CG [9]. There is very little information in literature on the clinical behaviour, treatment and prognosis of secondary forms of CG, but these might be determined by the underlying disease. In conclusion, this report highlights the close association of ischaemia with CG and further expands the spectrum of associations of this renal lesion.

Hepatic biotransformation of gut microbiota-derived trimethylamine (TMA) to trimethylamine N-oxide (TMAO) may enhance cardiovascular risk [1, 2]. The source of TMA is fish-derived TMAO [3], meat-derived betaine/choline/phosphatidylcholine [1, 2], and the medicine l-carnitine [4]. There is no clear information on the metabolic fate of TMA/TMAO in patients receiving hemodialysis and treated with l-carnitine orally and intravenously. We report data showing that plasma TMA/TMAO concentrations in hemodialysis patients may be in the same range as those of healthy subjects consuming a typical diet in Japan. Fourteen subjects, randomly selected from a cohort of 18 male and 6 female Japanese patients (47–89 years) with diabetes mellitus or chronic glomerulonephritis who had undergone hemodialysis for several years, were divided into five untreated controls, five treated with 1000 mg of l-carnitine (l-Cartin injection, Otsuka, Tokyo, Japan) intravenously on 3 days (Days 1, 3 and 5) over 1 week, and four treated with 300 mg of oral l-carnitine (l-Cartin tablets, Otsuka) three times per day for 7 days. Ten healthy volunteers (22–59 years) were also enrolled. This study was approved by the ethics committees of Minami Ikebukuro Clinic and Showa Pharmaceutical University. Total carnitine and TMA/TMAO concentrations were determined by Kainos laboratories (Tokyo, Japan) and by gas chromatography [3]. Carnitine concentrations for 2–8 weeks after treatment with l-carnitine were significantly higher than those in the untreated group (Figure 1). Plasma TMA concentrations after oral treatment with l-carnitine were higher than those of the untreated group. TMAO concentrations did not increase significantly after treatments and were in the range of daily interindividual variations. In separate observations in 22 of the 24-patient cohort, pre-dialysis plasma concentrations of carnitine (33 ± 4 µM, mean ± SD), TMA (34 ± 20 µM) and TMAO (189 ± 94 µM) were decreased by hemodialysis (12 ± 8, 25 ± 8 and 140 ± 77 µM, respectively). These concentration ranges were comparable with TMA (26 ± 17 µM) and TMAO (197 ± 100 µM) in healthy volunteers (n = 10). The present plasma levels of TMA and/or TMAO in Japanese patients were one or two orders of magnitude higher than the reported concentrations in Caucasians [1, 2], but were consistent with a review of patients undergoing hemodialysis [4]. Fig. 1. Plasma concentrations of total l-carnitine (A), TMA (B) and TMAO (C) in untreated patients (circles) and in patients treated with l-carnitine intravenously (triangles) and orally (squares). The three bars are averages of the three groups (n = 4 or 5). ... Some TMA formation in a Japanese cohort treated with l-carnitine orally was confirmed, but the levels of TMA/TMAO both pre-/post-dialysis in patients not receiving l-carnitine were in the same ranges as those of the control subjects.

Take home message The duration of exposure to environmental hypoxia during physical exercise is a potential mediator of immune function and athletic performance. Continuous hypoxic training resulted in overt immunodepression whereas intermittent hypoxic training increased physical exercise performance considerably. Although most elite athletes invest a considerable amount of time and resources training at altitude, the practical benefits gained remain to be clearly established despite almost half a century of investigation. Elucidating the potential factors that affect physical performance after return to sea level has been the subject of much interest and controversy. The time spent exposed to the hypoxia of altitude would appear to be an important mediator of sea level performance. A combination of physical exercise and intermittent hypoxia (defined as an exposure time of 30 minutes to 12 hours a day) has been shown to accelerate the normal adaptations invoked by a comparable programme of normoxic training with cardioprotective and performance enhancing benefits.1 In contrast, increased free radical mediated oxidative stress,2 decreased cell mediated immunity,3 and increased incidence of infectious episodes4 have been reported in continuous hypoxia (defined as an exposure time of 24 hours a day). We have previously reported two cases of infectious mononucleosis following chronic exposure to 1500–2000 m.5 Glutamine has been identified as a conditionally essential amino acid required for lymphocyte proliferation and macrophage phagocytosis, and it has been suggested that any physiological decrease in plasma glutamine may impair the host's defence against opportunistic infections.6 In the light of these findings, …

Background—There is a dearth of evidenced based research into sports injury in professional cricket. Aim—To investigate the incidence, nature, and site of acute injuries sustained by professional cricketers at one English county club over the period 1985–1995. Methods—Injuries in a sample of 54 cricketers who had played in the first team for the same county cricket club in any or all seasons between 1985 and 1995 were investigated. Injury was defined as the onset of pain or a disability resulting from either training for or playing cricket, which caused the player to seek medical attention. Results—An acute injury rate of 57.4 injuries per 1000 days of cricket played was found, with most injuries sustained during April, the month in which the least number of days were played. The lower limb was the region most vulnerable to injury, accounting for 44.9% of all injuries, followed by the upper limb (29.4%), the trunk (20.0%), and the head and neck (5.7%). No significant difference in injury incidence among player positions was found. Conclusion—There is a need for a system of epidemiological data collection and development of a national cricket injury database to help predict, reduce, and prevent injury at all levels of the game. Key Words: cricket; injury

A rise in serum creatinine without acute kidney injury (AKI) is possible. In the last 5 years, three patients presented to us for high serum creatinine levels after binge drinking. We already reported on two of these three patients [1, 2]. For the first one, dialysis was instituted as the initial diagnosis was AKI. With the experience gained, the next two patients were examined specifically for a particular cause. They were not dialyzed. The data of the third patient were as follows: a 44-year-old male, admitted after a fall following binge alcohol consumption. He complained of painful abdominal distension and was anuric. Serum creatinine was 6.5 mg/dL (575 µmol/L), blood urea: 66 mg/dL (23.5 mmol/L), serum sodium 134 mmol/L and serum potassium 4.3 mmol/L. An abdominal ultrasound examination showed two normal kidneys, a normal urinary tract and presence of peritoneal fluid. In view of these findings, a bladder rupture was suspected and confirmed by cystoscopy. With bladder drainage, serum creatinine diminished to 3.5 and then 1.4 mg/dL (309–123.7 µmol/L). Laparotomy was done and a 4-cm tear on the dome of urinary bladder was surgically repaired. All three patients had similar histories: (i) an alcoholic binge, (ii) a trauma, (iii) sudden onset of abdominal pain and progressive distension (iv) anuria (v) elevated serum creatinine (vi) cystography revealing a tear in the bladder and (vii) improvement in serum creatinine on continuous bladder drainage. The data of these patients are given in supplementary Table S1. In the majority of bladder ruptures, there is a history of significant abdominal trauma. Following heavy alcohol intake, the distended bladder is very susceptible to injury and can be ruptured by a minor trauma. Alcohol-induced polyuria and impaired sensorium that removes cues for voiding cause overdistension of the bladder and rupture. The intoxicated patient may fail to recall the trauma. In a review of 20 isolated intraperitoneal bladder ruptures, the mean time between presentation and diagnosis was 5.4 days [3]. The diagnosis was based on a compatible history: suprapubic pain, anuria, hematuria and rapidly increasing ascites. The diagnosis was strengthened by rapidly rising serum creatinine without features of hypercatabolism. Continuous bladder drainage normalized laboratory abnormalities. Urinary bladder injuries after blunt or penetrating trauma are rare, owing to the bladder's anatomical position [4]. Bladder ruptures can be extraperitoneal, intraperitoneal or both, depending on the site of the injury. Intraperitoneal bladder ruptures are usually associated with blunt abdominal trauma (excluding iatrogenic causes), and unlike extraperitoneal leaks, they are not usually associated with pelvic fractures. Intraperitoneal ruptures usually occur at the dome of the bladder in contrast to extraperitoneal leaks which are most often lateral [4]. Non-traumatic rupture is even rarer and causes may be essentially divided as increase in intravesical pressure or weakening of the bladder wall. In most cases, spontaneous rupture occurs in the presence of a urothelial neoplasm or after pelvic radiation therapy [2]. In neonates, peritoneal entry of urine is a rare complication. The major causes are congenital obstructive uropathy with urine leakage into the peritoneal cavity and bladder perforation as a complication of umbilical artery catheterization [5]. The expression ‘reverse peritoneal dialysis’ was first used in 1991 [5]. It is characterized by a flux of small molecules such as creatinine and urea from urine collected in the peritoneum along a concentration gradient opposite to conventional peritoneal dialysis where small molecules move from the blood to peritoneal cavity, a phenomenon mentioned as ‘reverse autoperitoneal dialysis’. As a result, the blood values of creatinine and urea are elevated mimicking renal failure despite normally functioning kidneys. This was described as ‘pseudo acute renal failure’ in the literature.

Torregrosa reports a rare case of dramatic increase in intact parathyroid hormone (iPTH) and hypocalcaemia after administration of denosumab in a kidney-transplanted patient [1]. However, the author does not comment on another important finding of this case which is the unusually prolonged hypocalcaemia. In the only study to have investigated this issue so far, Block et al. report that in the chronic kidney disease (CKD) 4 subgroup, adjusted serum calcium (ACa) levels return to normal within 15 days [2], but in Torregrosa's report the patient still remains hypocalcaemic 6 months after denosumab [1]. We report a similar case of a 64-year-old female with an allogeneic renal transplant 3 years prior to presenting to the clinic with stable CKD4 and tertiary hyperparathyroidism, and presented with sustained multiple fragility fractures secondary to osteoporosis. Her medication included alfacalcidol 500 ng daily, cinacalcet 60 mg daily, tacrolimus, and prednisolone. Biochemistry was as follows: ACa 2.37 mmol/L (9.48 mg/dL) (always within the normal range in the last year), estimated glomerular filtration rate (eGFR) 16 mL/min/1.73 m2, iPTH >190 pmol/L (1.79 ng/dL) and 25(OH)vitamin D 34.2 nmol/L (13.7 ng/mL). Following administration of denosumab 60 mg, ACa concentrations decreased to 1.96 mmol/L (7.84 mg/dL) at Day 16, returning to normal at Day 93. iPTH remained persistently elevated at >100 pmol/L (943 pg/mL). Throughout this period, the patient had adequate dietary calcium intake and did not change medication. Block also reports that in the CKD 5 subgroup, ACa returns to normal by Day 60 after denosumab [2]. We report an unusually prolonged (almost 5 months) and poor response to treatment for hypocalcaemia following administration of 60 mg denosumab in a patient with CKD5. A 64-year-old female presented with osteoporosis and a femoral fragility fracture. Past medical history included CKD5 secondary to IgA nephropathy, 11 years of haemodialysis treatment, tertiary hyperparathyroidism and treated non-metastatic breast cancer. Medication included cinacalcet 60 mg daily, alfacalcidol 1 µg daily and letrozole (all taken long term in an unchanged dose). Biochemistry was as follows: ACa 2.45 mmol/L (9.8 mg/dL) (always within the normal range in the last 12 months), eGFR 9 mL/min/1.73 m2 and PTH 54.8 pmol/L (517 pg/dL). Following denosumab, ACa decreased to 1.97 mmol/L (7.88 mg/dL) at Day 30 and remained low for the following 3 months [2.04 mmol/L (8.16 mg/dL) at Day 91]. Similarly to Torregrosa's case, iPTH rose from 54.8 to 108 pmol/L (1.02 ng/dL) at the nadir of hypocalcaemia. Throughout this period, medication and dialysis settings were not changed and the patient had adequate dietary calcium intake. On Day 91, alfacalcidol was increased to 4 µg daily and cinacalcet was reduced to 30 mg daily, but this resulted in only a modest improvement in ACa to 2.26 mmol/L (9.04 mg/dL) at Day 139. From our two cases and from Torregrosa's case, it appears that hypocalcaemia following denosumab can be more prolonged than previously thought even with adequate calcium and vitamin D supplementation. We hypothesized that in our two cases, the prolonged hypocalcaemia was due to the combined effect of denosumab and cinacalcet, both of which are known to lower serum calcium levels. However, Torregrosa's case points out that there might be other possible causes and there is scope for further studies.

The approval of febuxostat, a non-purine analogue inhibitor of xanthine oxidase, by the European Medicines Agency and US Food and Drug Administration, heralds a new era in the treatment of gout [1]. The most commonly reported adverse drug reactions were liver function abnormalities, diarrhoea, headache, nausea, and dizziness and/or altered taste. Only one case of cutaneous leukocytoclastic vasculitis has been reported with febuxostat [2]. In this report, we provide the first case of anti-neutrophil cytoplasmic antibody (ANCA)-positive pauci-immune glomerulonephritis (PIGN) during febuxostat treatment.

Rupture of the peritoneal catheter extension is a rare complication in peritoneal dialysis. We report a case of a 75-year-old male with chronic kidney disease of unknown aetiology on continuous ambulatory peritoneal dialysis for 5 months. While manipulating the catheter for the drainage of the first exchange in the morning, the catheter extension broke. In order to not interrupt the drainage, the patient inserted a cylinder of plastic, a straw he had found in his home, as shown in the picture (Figure ​(Figure1).1). The quality of this home remedy showed more than acceptable results, due to the similarity of the cylinder with the catheter in terms of thickness and consistency, so the patient could complete the drainage and the next infusion. Fig. 1. Home remedy with a straw as part of the catheter extension. Once the patient was disconnected, he came to our peritoneal dialysis unit for the replacement of the catheter extension, proud of having solved the problem himself. Prophylactic antibiotic and antifungal treatment was prescribed and the patient, fortunately, did not develop peritonitis. Was this a work of genius or a work of madness?

A previously healthy, 35-year-old woman, mother of two children, presented with a 3-day history of abdominal discomfort, vomiting and anuria for 2 days. She had no history of diabetes or hypertension. She had been using a combination of ethinylestradiol and drospirenone as a contraceptive for the previous 3 years. Her investigations at presentation were: serum creatinine: 7.9 mg/dL (698 μmol/L), blood urea nitrogen: 185 mg/dL (66 mmol/L), serum proteins: 8.2 g/dL, serum albumin: 4.5 g/dL, serum homocysteine: 4.2 μmol/L (0.56 mg/L), haemoglobin: 11.2 g/dL, total leucocyte count: 4800/mm3, platelet count: 340 × 109/L, prothrombin time: 15.0 sec (control: 13.0 sec), activated partial thromboplastin time: 28.0 sec (control: 30.0 sec), thrombin time: 10.0 sec (control: 8.0 sec), bleeding time: 4.0 min (reference range: 2.0–7.0 min), clotting time: 5.0 min (reference range: 5.0–7.0 min), serum fibrinogen: 444 mg/dL (range: 150–400 mg/dL) and D-dimer: 1.7 μg/mL (range: 0.5 μg/mL). Kidney sizes on ultrasound were right: 12.4 × 4.6 cm and left: 11.5 × 4.4 cm. Doppler of the renal arteries revealed severe decrease and pruning of the segmental, inter-lobar and arcuate vessels and absence of the cortical blush in both of the kidneys. Urine dipstick examination for proteins was negative. A renal biopsy was done after a session of haemodialysis. It revealed coagulative necrosis (infarct) of the cortex of the kidney, and the artery included in the biopsy was obstructed by fibrin thrombus (Figure 1). She was not pregnant and had no congenital heart disease. There was no history of acute gastroenteritis, trauma or snakebite. There was no history or clinical features suggestive of haemolytic uraemic syndrome. There were no schistocytes on peripheral smear. Electrocardiogram showed normal sinus rhythm with no ischaemic or chamber enlargement changes. Echocardiography revealed normal cardiac chambers and normal valves. The reports of anti-thrombin III: 0.25 g/L (range: 0.19–0.31 g/L), protein C: 90% (range: 70–160%) and protein S: 80% (range: 60–150%). Prothrombin time and partial thromboplastin times were not prolonged in order to investigate for factor V Leiden mutation. Flow cytometry did not find a reduction in CD 55 and CD 59 on red blood cells, thus excluding paroxysmal nocturnal haemoglobinuria. Anti-phospholipid antibodies, lupus antibody, anti-nuclear antibodies and anti-double-stranded DNA were negative. Fig. 1. Renal biopsy showing cortical necrosis and the artery occluded by fresh fibrin thrombus (arrow) in an artery (SMPASX40). The patient did not regain renal function. She was initiated on continuous ambulatory peritoneal dialysis. One of the adverse effects of oral contraceptive pills is arterial thrombosis. There are experimental reports of acute cortical necrosis in rats induced by oestrone and vasopressin administration [1]. There are a few reports of acute cortical necrosis in patients who used oral contraceptives, but these patients had other features like factor V Leiden mutation [2] and smoking [3].

Sir, The importance of renal function in the prognosis of patients with multiple myeloma (MM) has been well established and rapid reversal of renal failure may offer the best long-term outcome. The use of extracorporeal means of removing immunoglobulin free light chains (FLCs) responsible for cast nephropathy in patients with MM is controversial. Nephrologists are interested in a treatment strategy combining chemotherapy and extracorporeal treatments in patients with biopsy-proven cast nephropathy or a high probability of cast nephropathy (defined as >200 mg/dL on the FLC assay). Some previous studies have shown that the plasma exchange is unable to remove sufficient FLCs for clinical benefits. The issue of whether an extended duration of dialysis with high cut-off (HCO) dialysers is more effective than plasma exchange at removing FLC or reversing renal failure is not settled [1]. Hutchison and Leung reported that a 60% reduction in FLCs by Day 21 is associated with recovery of renal function for 80% of the studied patients [2]. Our experience: a 43-year-old man, who was not complaining of any previous disease and with a previously normal renal function, suffering from biopsy proven lambda myeloma kidney, without any histological sign of chronic renal damage, and renal failure dialysis dependant, in 2 weeks received 10 haemodialysis (HD) treatments with HCO-dialyser (Theralite Gambro). We quantified the concentration of FLCs by nephelometry (Biocite, N latex test; Siemens). Initially, λ FLC concentration was 5500 mg/L. At the end of HCO dialyser HD cycle, the concentration was 94.80 mg/L (Table 1). Table 1. Concentrations and ratios of FLC before and after HCO-dialyser HDa We did not observe any adverse effects. We observed by Day 7 a sustained and >50% reduction of FLCs with dialysis alone before the chemotherapy was initiated. After the third HCO-dialyser HD, the patient started PAD Orlowsky chemotherapy (Bortezomib–Doxorubicin–Dexamethasone) with successful haematological result but with partial renal function recovery. Currently (5 months after HCO-dialyser treatment), the patient is on maintenance HD two times a week. Some reports show a recovery of renal function after several months. If the patient does not recover normal renal function, we think that a new kidney biopsy can help his management.

Stress fractures of the rib have been reported in rowers1–3 and canoeists4–5; this is the first report of a similar fracture in a golfer.