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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.

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

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.

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 …

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

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.

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.

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, …

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.

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.

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].