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Acute kidney injury (AKI) is common among hospitalized patients with Coronavirus Infectious Disease 2019 (COVID-19), with the occurrence of AKI ranging from 0.5% to 80%. The variability in the occurrence of AKI has been attributed to the difference in geographic locations, race/ethnicity, and severity of illness. AKI among hospitalized patients is associated with increased length of stay and in-hospital deaths. Even patients with AKI who survive to hospital discharge are at risk of developing chronic kidney disease (CKD) or end-stage kidney disease (ESKD). An improved knowledge of the pathophysiology of AKI in COVID-19 is crucial to mitigate and manage AKI and to improve the survival of patients who developed AKI during COVID-19. The goal of this article is to provide our current understanding of the etiology and the pathophysiology of AKI in the setting of COVID-19.

Background The coronavirus disease 2019 (COVID-19) may be associated with kidney injury, which may impact patient's prognosis. Methods We report a multicentric retrospective case series of patients with COVID-19 who developed acute kidney injury (AKI) and/or proteinuria and underwent a kidney biopsy in Paris and its metropolitan area. Results Forty-seven patients (80.9% men) with COVID-19 who underwent a kidney biopsy between 8 March and 19 May 2020 were included. The median age was 63 years (interquartile range 52–69). Comorbidities included hypertension (66.0%), diabetes mellitus (27.7%), obesity (27.7%), history of chronic kidney disease (25.5%), cardiac diseases (38.6%) and respiratory diseases (27.3%). Initial symptoms were fever (85.1%), cough (63.8%), shortness of breath (55.3%) and diarrhoea (23.4%). Almost all patients developed AKI (97.9%) and 63.8% required renal replacement therapy. Kidney biopsy showed two main histopathological patterns, including acute tubular injury in 20 (42.6%) patients, and glomerular injury consisting of collapsing glomerulopathy (CG) and focal segmental glomerulosclerosis in 17 (36.2%) patients. Two (4.3%) patients had acute vascular nephropathy, while 8 (17%) had an alternative diagnosis most likely unrelated to COVID-19. Acute tubular injury occurred almost invariably in the setting of severe forms of COVID-19, whereas patients with glomerular injury had various profiles of COVID-19 severity and CG was only observed in patients harbouring a combination of APOL1 risk variants. At the last follow-up, 16 of the 30 patients who initially required dialysis were still on dialysis, and 9 had died. Conclusions This study describes the spectrum of kidney lesions in patients with COVID-19. While acute tubular injury is correlated with COVID-19 severity, the pattern of glomerular injury is intimately associated with the expression of APOL1 risk variants.

The aim of this study was to estimate the incidence of COVID-19 disease in the French national population of dialysis patients, their course of illness and to identify the risk factors associated with mortality. Our study included all patients on dialysis recorded in the French REIN Registry in April 2020. Clinical characteristics at last follow-up and the evolution of COVID-19 illness severity over time were recorded for diagnosed cases (either suspicious clinical symptoms, characteristic signs on the chest scan or a positive reverse transcription polymerase chain reaction) for SARS-CoV-2. A total of 1,621 infected patients were reported on the REIN registry from March 16th, 2020 to May 4th, 2020. Of these, 344 died. The prevalence of COVID-19 patients varied from less than 1% to 10% between regions. The probability of being a case was higher in males, patients with diabetes, those in need of assistance for transfer or treated at a self-care unit. Dialysis at home was associated with a lower probability of being infected as was being a smoker, a former smoker, having an active malignancy, or peripheral vascular disease. Mortality in diagnosed cases (21%) was associated with the same causes as in the general population. Higher age, hypoalbuminemia and the presence of an ischemic heart disease were statistically independently associated with a higher risk of death. Being treated at a selfcare unit was associated with a lower risk. Thus, our study showed a relatively low frequency of COVID-19 among dialysis patients contrary to what might have been assumed., Graphical abstract

Over the last three decades, advancements in the diagnosis, treatment, and supportive care of patients with cancer have significantly improved their overall survival. However, these advancements have also led to a higher rate of cancer-related complications. Acute kidney injury (AKI) and chronic kidney disease (CKD) are highly prevalent in patients with cancer, and they are associated with an increased risk of all-cause mortality. This bidirectional interplay between cancer and kidney, termed “the kidney–cancer connection” has become a very active area of research. This review aims to provide an overview of some of the most common causes of AKI in patients with cancer. Cancer therapy-associated AKI is beyond the scope of this review and will be discussed separately.

Background Renal biopsy is the cornerstone of Lupus nephritis (LN) management. However, transcutaneous renal biopsy (TCRB) is hampered by the antithrombotic treatment frequently prescribed in Systemic Lupus Erythematosus (SLE) and Antiphospholipid Antibody Syndrome (APS). Transjugular renal biopsy (TJRB) offers an attractive alternative for patients at increased risk of bleeding. Objectives The primary objective of the study was to describe the safety and the diagnostic performance of TJRB in SLE and APS. Methods A retrospective review of SLE and/or APS patients who consecutively underwent a renal biopsy in our department between January 2004 and October 2016 was performed. Biopsies were divided into four groups: TCRB, TJRB with aspirin treatment (aspirin TJRB), TJRB with anticoagulant treatment (anticoagulant TJRB), and TJRB without anti-thrombotic drug (no-antithrombotic TJRB). Major complications were defined as decease, haemostasis nephrectomy, renal artery embolization, blood transfusion, sepsis and vascular thrombosis. Minor complications were defined as gross haematuria, renal hematoma and arterio-venous fistula. Results Fifty-four TCRB and 256 TJRB were analysed – 69 aspirin TJRB, 68 anticoagulant TJRB and 119 no-antithrombotic TJRB. Major complications rate was 1.9% for TCRB and 2.0% for TJRB (p=1). One patient in the TJRB group suffering from catastrophic antiphospholipid syndrome (CAPS) died suddenly 6 weeks after the biopsy. No patient died of bleeding complication. One patient in the anticoagulant TJRB group required a renal artery embolization and blood transfusion. Four other patients required blood transfusion (1 in the TCRB group, 1 in the aspirin TJRB group and 2 in the anticoagulant TJRB group). Minor complications rate was 1.9% for TCRB and 7.8% for TJRB (p=0.2). Among the 256 TJRB, the rate of complication (major or minor) was higher for patients with glomerular filtration rate CKD-EPI 30 mL/min (16/232 [7%], p 140/90 mmHg, APS or positive antiphospholipid biology without APS, Prothrombin Time 1.2, platelets The number of glomeruli sampled and the performance of the biopsy to establish a histologic diagnostic were similar in the 4 groups. Conclusions TJRB provides diagnostic yield and safety similar to those of TCRB. It should be considered as a first intention procedure for SLE and APS patients at risk of bleeding. Disclosure of Interest None declared

Resume La nephropathie diabetique (ND) est une cause majeure de maladie renale chronique dans le monde. Le traitement de reference necessite l’equilibre glycemique, la normalisation de la pression arterielle et de la proteinurie en utilisant les agents hypoglycemiants, les inhibiteurs de l’enzyme de conversion (IEC) de l’angiotensine ou des bloqueurs des recepteurs de l’angiotensine II. Depuis 2000, de nouvelles strategies therapeutiques ont commence a emerger, ciblant l’activite biochimique des molecules de glucose sur le tissu renal. Diverses substances ont ete etudiees avec differents degres de succes, allant de la vitamine B au lait de chameau. Le silymarin reduit l’excretion urinaire d’albumine, le tumor necrosis factor (TNF)-α et le malondialdehyde chez les patients presentant une nephropathie diabetique, et peut etre considere comme une nouvelle molecule additive de l’arsenal anti-nephropathie diabetique. Bien que certains resultats semblent prometteurs, des etudes a plus grande echelle sont necessaires afin de determiner l’utilite des molecules actuellement en developpement dans le traitement de la ND.

Tetracyclines are broad-spectrum antibiotics that interfere with protein synthesis. They were first widely prescribed by dermatologists in the early 1950s in the treatment of acne. More recently, their biological actions on inflammation, proteolysis, angiogenesis, apoptosis, metal chelation, ionophoresis, and bone metabolism were studied. Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that degrade components of the extracellular matrix (ECM). MMPs have direct or indirect effects on the vascular endothelium and the vascular relaxation/contraction system. The therapeutic effects of tetracyclines and analogues were studied in rosacea, bullous dermatoses, neutrophilic diseases, pyoderma gangrenosum, sarcoidosis, aortic aneurysms, cancer metastasis, periodontitis and autoimmune diseases autoimmune diseases such as rheumatoid arthritis and scleroderma. In addition, downregulation of MMP using doxycycline could be beneficial in reducing vascular dysfunction mediated by MMPs and progressive damage of the vascular wall. We review the nonantibiotic properties of doxycycline and its potential clinical applications.

Kimura's disease (KD) is an angiolymphoid proliferative disorder of soft tissue with eosinophilia, with a predilection for head and neck regions in young Oriental men. Kidney disease is thought to be rare in KD. About a case of adult-onset nephrotic syndrome with minimal change disease, we comment Kimura's disease and its associated kidney damage. Kimura disease should be suspected and included in the diagnosis of adult-onset nephrotic syndrome with minimal change disease.

Arterial hypertension (HTN) is a class effect of anti-vascular endothelial growth factor (VEGF) therapies, including the monoclonal antibody bevacizumab. Data are conflicting regarding the role of the renin-angiotensin system on angiogenesis and recent data suggest that the use of angiotensin system inhibitors (ASIs; angiotensin receptor blockers or angiotensin-converting enzyme inhibitors) is associated with improved survival in metastatic renal cell carcinoma (mRCC), particularly when used with VEGF targeted therapies. The aim of this review is to discuss the available treatment options for mRCC and associated incidence of hypertension as well as summarize the known data about ASIs use and mRCC. Additionally, given that the optimal management of HTN remains unclear, we will focus on prevention strategies and propose potential therapeutic approaches.

Resume Le syndrome hepatorenal (SHR) est une complication severe de la cirrhose. Il resulte d’anomalies hemodynamiques associant une vasodilatation systemique et une vasoconstriction renale. Le risque infectieux augmente, la mise en jeux des systemes vasoconstricteurs et le syndrome de reponse inflammatoire systemique contribuent a la dilatation splanchnique et a l’alteration de l’autoregulation renale. Une fraction d’ejection cardiaque inadaptee et une incompetence systolique augmentent le risque d’insuffisance renale. Le SHR de type I est habituellement initie par un evenement precipitant associe a une reponse inflammatoire systemique exageree resultant en une defaillance multiviscerale. Les vasoconstricteurs sont le traitement de base au cours du SHR de type I avec en chef de file la terlipressine. La norepinephrine peut etre utilisee comme une alternative therapeutique. Le shunt porto-cave intrahepatique transjugulaire (TIPS) peut etre applicable chez un petit nombre de patients avec SHR de type I et dans la majorite des patients avec SHR de type II. La transplantation hepatique est le traitement definitif du SHR. La decision d’une bigreffe rein/foie ou d’une transplantation sequentielle foie puis rein reste tres controversee. En pratique, les patients ayant besoin de plus de huit a 12 semaines de dialyse pretransplantation doivent etre consideres pour une bigreffe rein/foie.

Background The protein kinase mTOR (mammalian target of rapamycin) is a critical regulator of cellular metabolism, growth, and proliferation. Inhibitors of mTOR have immunosuppressive and anti-cancer effects, but their effects on the progression of kidney disease are not fully understood. Their most common side-effects include stomatitis, rash, dyslipidemia, hyperglycemia, fatigue, and pneumonitis. However, to the best of our knowledge these agents have not been previously reported to cause severe acute kidney injury (AKI). Case presentation We describe four cases of patients with cancer who developed AKI after starting mTOR inhibitor therapy. A kidney biopsy showed acute tubular necrosis (ATN) with prominent tubular dysfunction. Withdrawal of the drug leads to a rapid recovery in two cases. However, a fixed renal dysfunction was noted in the other two cases, one of which will remain dialysis-dependent. Such patients lead to a broad differential diagnosis of AKI including prerenal AKI, ATN, cancer-related GN, and drug-induced acute interstitial nephritis. Accurate history, physical examination, laboratory data, and kidney biopsy are highlighted in establishing the correct diagnosis in such patients. Conclusions ATN have not been reported with mTOR inhibitor use. These cases demonstrated a potentially new and serious adverse consequence occurring with the use of an mTOR inhibitor, of which physicians need to be aware.

Thyroid hormones influence renal development, kidney structure, renal hemodynamics, glomerular filtration rate, the function of many transport systems along the nephron, and sodium and water homeostasis. Effects of hypothyroidism and hyperthyroidism on kidney function are the result of direct renal effects, as well as systemic hemodynamic, metabolic, and cardiovascular effects. Most of the renal manifestations of thyroid disorders, which are clinically most significant with hypothyroidism, are reversible with treatment. Patients with hypothyroidism can have clinically important reductions in GFR, so screening for hypothyroidism should be considered in patients with unexplained elevations in serum creatinine. Patients with thyroid disorders are also at risk for immune-mediated glomerular diseases. Finally, patients with nephrotic syndrome, as well as acute and chronic kidney injury, have alterations in thyroid gland physiology that can impact thyroid function and the testing of thyroid function status. Dialysis patients have frequently hypothyroidism whose biological diagnosis must be careful.

The hypereosinophilic syndromes (HESs) are a group of disorders marked by the sustained overproduction of eosinophils, in which eosinophilic infiltration and mediator release cause damage to multiple organs. In idiopathic HES, the underlying cause of hypereosinophilia (HE) remains unknown despite thorough aetiological work-up. Kidney disease is thought to be rare in HES. Renal manifestations described include eosinophilic interstitial nephritis, various types of glomerulopathies, thrombotic microangiopathy (TMA) and electrolyte disturbances. The diagnosis must be made in time, because a recovery of renal function can be obtained if treatment is initiated promptly.

Oncologists and nephrologists usually manage proteinuria related to anti-vascular endothelial growth factor (anti-VEGF) treatment only when it is in the nephrotic range or associated with renal insufficiency. This report is based on our personal experience with 78 patients developing renal problems with anti-VEGF therapy. We found that proteinuria induced by anti-VEGF therapy, even if weak and without associated renal insufficiency, may reflect a serious histological renal disease.

We report a case of renal thrombotic microangiopathy (TMA) in a myeloproliferative variant of hypereosinophilic syndrome (HES) in a 24-year-old man which resolved with imatinib therapy. This is one of a few cases in the literature to date describing TMA in HES, suggesting that the pathogenesis of thrombosis is at least in part related to damage from activated eosinophils.

Background Cardiotoxicity of Molecular Targeted Therapies (MTT) is poorly understood and is being investigated among patients with metastatic solid tumours. The frequency of cardiac events among patients receiving MTT has been evaluated in various ways, particularly troponin elevations. Patients and methods We prospectively evaluated cardiotoxicity among patients included in Phase 1 trials receiving molecular targeted therapies (MTT) for a metastatic solid tumour. At baseline, all patients were examined before the first cycle and monitored including a clinical examination, ECG and troponin I measurement. A trans-thoracic echocardiography was performed at baseline and before each cycle. Patients were enrolled in different trials investigating : an anti-VEGF monoclonal antibody, anti-VEGFR tyrosine kinase inhibitors, and a kinesin inhibitor. Results Among the 90 patients evaluated, 10 (11%) experienced chest pain and troponin I elevation (n = 2,20%) or asymptomatic troponin I elevation (n = 8, 80%) during follow-up. All patients were re-evaluated at the time of symptoms or troponin I elevation with trans-thoracic echocardiography, cardiac magnetic resonance and coronary angiography. All except one patient, had a normal LVEF during their re-evaluation. One patient exhibited ECG changes (T wave inversion). No QTc interval prolongation was found. On cardiac magnetic resonance, no late gadolinium myocardial enhancement was observed. All coronary angiographies were normal (no occlusion, or coronary stenosis >50%). All patients received beta blockers and aspirin. All Patients were re-challenged with the study drug and no cardiotoxicity was observed during follow up. Conclusion Troponin elevations are frequent among patients receiving molecular targeted therapies. Re-challenging these patients after a careful evaluation and under medical treatment seems to be possible. The mechanism underlying troponin elevations does not seem to be associated with coronary occlusion nor with toxic myocarditis.

Background. HIV-associated nephropathy (HIVAN) is usually diagnosed in virologically uncontrolled infected patients. However, HIVAN can occur in some cases with undetectable HIV-1 RNA levels. We suggested that intracellular HIV-1 proviral DNA load can be used as a marker in this particular patient population. Methods. Renal tissue HIV-1 proviral DNA, peripheral blood mononuclear cells (PBMCs) HIV-1 proviral DNA, plasma HIV-1 RNA and peripheral blood CD4-positive lymphocyte counts were quantified and assessed in 100 HIV-1-infected individuals (49 with undetectable HIV-1 RNA level viraemia) who underwent a kidney biopsy for renal abnormalities in a prospective study. Results. A proviral DNA load was detected in patients with HIV-1-associated nephropathy with a negative plasma viral RNA load. None of the patients with a proviral DNA load of

It is now clearly established that anti-vascular endothelial growth factor (VEGF) drug class induces hypertension and proteinuria sometimes related to thrombotic microangiopathy and/or various glomerulopathies, according to capillary and glomerular VEGF and VEGF-receptor expressions. As reported in the literature, anti-epidermal growth factor receptor (EGFR) therapies seem to be less nephrotoxic. Indeed, many reports of anti-EGFR nephrotoxicity are tubular dependent such as acute tubular necrosis, electrolyte disorders (hypophosphatemia, hypomagnesemia, etc.) or both. This is explained by elective tubular expression of renal EGF/EGFR. In this paper, we focus on electrolyte disorders related to anti-EGFR treatment and discuss the tubular involvement of these drugs based on their renal expression.

Proteinuria is a dose-related side-effect occurring after inhibition of vascular endothelial growth factor (VEGF) signalling and may reflect severe glomerular damage. The inhibition of the VEGF signalling axis induces downexpression or suppression of nephrin, an important protein for the maintenance of the glomerular slit diaphragm, sometimes leading to nephritic syndrome and/or glomerular thrombotic microangiopathy, the main-associated kidney disease. A MEDLINE search was carried out using the following criteria: (1) all MEDLINE listings as of 01-01-2000 with abstracts; (2) English language; and (3) Humans. The following phrases were used to query the database: (proteinuria) AND (anti-VEGF OR VEGF inhibition OR bevacizumab OR sunitinib OR sorafenib OR VEGF Trap OR axitinib OR pazopanib OR AZ 2171). The references of each article identified were carefully reviewed for additional reference. The incidence of mild and asymptomatic proteinuria ranges from 21% up to 63%, but heavy proteinuria has been reported in up to 6.5% of renal cell carcinoma patients. Although discontinuation of anti-VEGF agent induced significant reduction, persistence of proteinuria is common. Although angiotensinconverting-enzyme inhibitors and/or angiotensin receptor blockers seem to be preferred, no specific recommendation for an antiproteinuric agent can be made in this context because there are no controlled studies addressing the subject. Periodic monitoring of urinary protein should be carried out in anti-VEGF-treated patients and patients showing proteinuria need special referral to nephrologists.

A patient is admitted in hospital to explore a nephrotic proteinuria associated with milky urine. This is explained by a chyluria (presence of lymphatic fluid in the urines), which is due to a pyelolymphatic fistula probably linked to a lymphatic filariasis. Usually, the diagnosis of chyluria can be confirmed by the presence of urinary chylomicrons. The presence of an urinary-lymphatic fistula can be proved by different techniques (cystoscopy, retrograde pyelography, uroscanner, lymphoscintigraphy). The main cause of chyluria is parasitic infections (filarial infection, echinococcus, cysticercosis), but other causes can be found, such as granulomatosis, neoplasia, lymphatic malformations, or sequela of surgery or traumatism. Chyluria is one of the causes of post-nephronic nephrotic proteinuria. Depending on the impact of the chyluria for the patient, there will either be no treatment, or a treatment by sclerotherapy or surgery.

With significant reductions in mortality and risk of progression to AIDS in the era of highly active antiretroviral therapy (HAART), complications of long-standing HIV infection and treatment have become increasingly important. Such complications include the nephrotoxic effects of HAART, which are the subject of this Review. The most common nephrotoxic effects associated with HAART include crystal-induced obstruction secondary to use of protease inhibitors (mainly indinavir and atazanavir), and proximal tubule damage related to the nucleotide analog reverse transcriptase inhibitor tenofovir. Acute kidney injury (AKI) can occur following tenofovir-induced tubule dysfunction or as a result of severe mitochondrial dysfunction and lactic acidosis induced by nucleoside reverse transcriptase inhibitors. The potential insidious long-term renal toxicity of antiretroviral treatment is probably underappreciated in patients with HIV: a proportion of patients with treatment-related AKI did not recover their baseline renal function at 2-year follow-up, suggesting the possibility of permanent renal damage. Finally, nonspecific metabolic complications might increase the risk of vascular chronic kidney disease in patients on HAART. However, given the benefits of HAART, fear of nephrotoxic effects is never a valid reason to withhold antiretroviral therapy. Identification of patients with pre-existing chronic kidney disease, who are at increased risk of renal damage, enables appropriate dose modification, close monitoring, and avoidance or cautious use of potentially nephrotoxic medications.

CASE PRESENTATION A 69-year-old man was admitted to hospital for the evaluation of refractory hypokalemia and metabolic alkalosis. The patient had a 1-year history of a stage pT4N0M1 non-small cell squamous lung carcinoma (NSCLC) that was managed by Pemetrexed (Alimta 500 mg/m 2 every 21 days) for the last 6 months. The patient had a 45-pack/y history of smoking without history of alcohol abuse, hypertension, or diabetes mellitus. He was married, had 2 children without health problems and used to work as a truck driver. He had no family history of cancer or metabolic problems. He was in his usual state of health until 1 month before admission. His medication list contained only paracetamol every 6 h.

Background: Hepatitis C virus (HCV) co-infection occurs in 25% of HIV-infected persons. The impact of HIV/HCV coinfection on renal and patient outcomes is unclear. Methods: The main objective of the study is the comparison of outcomes (progression to advanced renal failure, initiation of dialysis, and death) in patients with HIV (n = 40), HCV (n = 30) or coinfection (n = 30) during the period between January 1999 and December 2007. Results: Patients were predominantly white men with a mean creatinine clearance of 50.6 ± 32.2 ml per min per 1.73 m2. Membranoproliferative glomerulonephritis (MPGN) and HIV-associated nephropathy were found in 34 and 9%, respectively. Seventeen patients needed transitory or definitive hemodialysis after 2, 2.5, and 12 months in HIV/HCV (n = 5), HIV (n = 6) and HCV (n = 6) infections, respectively. In multivariate analysis, variables found to independently predict outcome in HIV/HCV coinfected patients were younger age, a longer delay to kidney biopsy, cryoglobulinemia and MPGN. Twenty-one patients died, mostly in the HCV (n = 8) and/or HIV/HCV coinfected (n = 12) groups. The relative risk of death for HIV/HCV co-infected patients was 2.1 times more than for HCV-infected patients and 7.5 times more than for HIV-infected patients. HIV/HCV co-infection [odds ratio (OR), = 4; 95% confidence interval (CI), 1.3–12.9; P = 0.015] and MPGN (OR, 6; 95% CI, 2–18.8; P = 0.0018) were independently associated with death. Conclusion: Kidney disease is a relatively frequent complication in HIV or HCV monoinfected individuals. The impact of kidney disease on survival of HIV/HCV coinfected patients seems deleterious but remains largely unknown.

Background Hypertension (HTN) is one of the most frequent side-effects of systemic inhibition of vascular endothelial growth factor (VEGF) signaling. Its incidence and severity are dependent on the type of drugs, dose, and schedule used. The recognition of this side-effect is an important issue because poorly controlled HTN could lead to serious cardiovascular events. On another hand, HTN induced by anti-VEGF agents maybe a predictive factor of oncologic response. Knowledge of this clinical toxicity and/or therapeutic target or novel biomarker of drug activity can aid clinicians choosing the optimal and least toxic regimen suitable for an individual patient. Methods A Medline search was carried out using the following criteria: (i) all Medline listings as of 1 January 2000 with abstracts, (ii) English language, and (iii) Humans. The following phrases were used to query the database: (‘hypertension’, OR ‘blood pressure’) AND (‘anti-VEGF’ OR ‘VEGF inhibition’ OR ‘bevacizumab’ OR ‘sunitinib’ OR ‘sorafenib’ OR ‘VEGF Trap’). The references of each article identified were carefully reviewed for additional reference. Results Lifestyle modification should be encouraged. However, these nonpharmacologic strategies are not always suitable to patients with altered performance status related to metastatic cancer necessitating early drug intervention. Only one randomized study showed a beneficial effect of a calcium channel blocker use to prevent or minimize HTN secondary to antiangiogenic therapy. Nitrates looks as effective in controlling such side-effect. Conclusions No clear recommendation for an antihypertensive agent can be made in this context because there is a lack of controlled studies addressing the subject. Blood pressure-lowering drugs should be individualized to the patient's clinical circumstances and angiogenic inhibitors should be withheld only from patients who experienced hypertensive crisis.

We report a patient with unknown primary undifferentiated carcinoma who developed acute renal failure associated with interstitial fibrosis following pemetrexed therapy. Despite drug withdrawal, renal function remained altered and the patient experienced chronic renal insufficiency. Pemetrexed disodium (Alimta™) is a multitargeted antifolate agent approved by the Food and Drug Administration (FDA) for patients diagnosed with mesothelioma and non-small cell lung cancer. This drug is almost exclusively cleared by renal excretion [1]. The most common side effects are hematologic dose-limiting toxicities and nonhematologic toxicities including fatigue, diarrhea, nausea, mucositis and rash. Although few cases of renal failure have been published, no study has reported on the renal pathological findings in this setting. We present a case of acute tubular necrosis associated with interstitial fibrosis after pemetrexed therapy.

Drug-induced acute interstitial nephritis (AIN) is an established cause of acute kidney injury (AKI). Antibiotics and non-steroidal anti-inflammatory drugs (NSAIDs) are the most frequent offending drugs [1]. Only a few vitamin K antagonist-induced AIN cases have been reported. Some publications describe AIN associated with fluindione (Previscan®), an anticoagulant of the antivitamin K family, derived from indanedione, exclusively marketed in France. We present an additional case of AIN secondary to fluindione and review the available literature. A 70-year-old woman was hospitalized for AKI. Her treatment list included amlodipine and atenolol. In December 2007, the serum creatinine (SCr) level was 70 μmol/L and an asymptomatic atrial fibrillation was detected. Fluindione was hence initiated. SCr rose to 220 μmol/L (04/08). On admission, her SCr level had reached 3.4 mg/dL and fluindione was stopped. Blood pressure was 110/ 80 mmHg, and neither cutaneous rash nor peripheral lymphadenopathy was found. Laboratory tests showed SCr 299.2 μmol/L, proteinuria 2 g/24 h (1 g albumin and low-molecular-weight proteins, each) and negative urine sediment. A renal ultrasound revealed reduced-sized (10 cm) kidneys without obstructive uropathy. Immunological analyses were negative. A transjugular renal biopsy was performed. The renal biopsy included 11 glomeruli; 5 were sclerotic and 6 were normal. A diffuse infiltrate of lymphocytes, eosinophils and monocytes was found in the interstitium associated with severe tubulitis (Figure ​(Figure1).1). Immunostains demonstrated CD3-positive lymphoid cells in the interstitium (Figure ​(Figure2)2) compared to CD20 immunohistochemical staining (Figure ​(Figure3).3). Immunofluorescence was negative. Electron microscopy was not performed. The diagnosis of fluindione-induced AIN (FI-AIN) was made. Despite withdrawal of the offending agent replaced by acenocoumarol, and oral corticosteroid therapy (1 mg/kg/day), renal function did not return to baseline values after 1 month (SCr, 259.6 μmol/L) but improved to 199.8 μmol/L 6 months later. Fig. 1 Renal biopsy specimen showing expansion of the renal interstitium by large lymphocyte inflammatory cell aggregates and severe tubulitis. Masson's trichrome stain; original magnification ×40. Fig. 2 Immunophenotyping analysis showing positive CD3 + T cells. Original magnification ×400. Fig. 3 Immunophenotyping analysis showing few CD20 + lymphocytes. Original magnification ×400. About 15% of the renal biopsies performed on patients with AKI demonstrate drug-induced AIN as the cause of the renal insufficiency. Only 13% of these patients showed the classic triad of rash, fever and eosinophilia. Discontinuation of the offending drug remains the first therapeutic step. Nevertheless, a considerable part of the affected patients may develop ESRD (23.4%). An important clinical prognostic factor is the average duration of the renal dysfunction; a cut-off point of 2–3 weeks seems relatively determining [1–3]. Few cases of vitamin K antagonist-induced AIN have been reported with warfarin, phenindione and fluindione [4]. Hypersensitivity reactions occur in 0.2–2% of cases [5]. Review of the literature revealed 16 biopsy-proven FI-AIN [5–11], including this case (Table ​(Table1).1). AKI appeared 7.5 ± 6.9 weeks (range 2–20) after introducing the offending drug. The average baseline SCr was (102.08 ± 35.2; range 62.5–149.6 μmol/L) obtained 7.5 ± 4.6 (range 0.5–16) months before the onset of FI-AIN. Fifty percent of patients showed proteinuria (0.3–19.7 g/24 h) associated with microscopic haematuria (12.5%) and leukocyturia (12.5%). The highest SCr reached between 135.52 and 824.56 μmol/L with a mean of 425.04 ± 243.76 μmol/L. Two patients (12.5%) required several sessions of haemodialysis [9]. Thirty-one percent (5/16) presented the classical triad of drug-induced AIN: fever, maculopapular rash and eosinophilia. The renal biopsy was obtained in 14 out of the 16 patients. In all cases, a diffuse inflammatory infiltrate composed of lymphocytes, eosinophils, monocytes and plasma cells invading the interstitial compartment was observed. Fluindione was withdrawn in all patients. Eleven patients (68.75%) were treated with steroids. Steroid doses and the duration of treatment were not uniform. The most common scheme consisted of oral prednisone (0.5–1 mg/kg/day) tapering off over 8–12 weeks. Intravenous pulses of methylprednisolone (250–500 mg daily for 3 days) were occasionally used. In 3 out of these 11 steroid-treated patients (27.3%), SCr never reached baseline values. The five patients who did not receive steroids had a complete recovery of baseline renal function 10 days to 3 weeks after withdrawal of the offending drug. However, the largest study to date by Gonzalez et al. demonstrated the beneficial effects of steroids for the treatment of drug-induced AIN, especially when initiated soon after withdrawal of the offending agent [1]. Table 1 Characteristics of patients with fluindione-induced acute interstitial nephritis

A 42-year-old white man was admitted to hospital with a 3-day history of progressive muscle weakness, myalgias and dark urines. He was HIV/hepatitis C virus (HCV) coinfected, with an absolute CD4+ T lymphocyte count of 393 cells/mm3, a serum HIV-1 RNA load of

Background A 58-year-old African American man with an uncontrolled HIV infection presented to hospital with nephrotic syndrome and diffuse lymphadenopathy. The patient had been taking highly active antiretroviral therapy (HAART; lamivudine, abacavir, fosamprenavir and ritonavir) for 10 years. A renal biopsy showed acute granulomatous interstitial nephritis. Despite a negative tuberculin skin test, he was treated with antituberculosis drugs for 12 months without improvement of his renal profile. Two months after antituberculosis treatment was discontinued, the patient was readmitted to hospital because of acute renal failure. Corticosteroid therapy (prednisone) was started and resulted in a marked improvement in renal function. However, 18 months after steroids were discontinued, renal function declined dramatically. Furthermore, the patient had CD8+ lymphocytosis as well as interstitial tissue infiltration by CD8+ T lymphocytes. Investigations Physical examination, plasma HIV viral load, lymphocyte counts, urinalysis, tuberculin skin test, liver function tests, renal ultrasonography, human leukocyte antigen (HLA) typing, renal and minor salivary gland biopsies, ophthalmological examination, chest radiography and culture of bronchoalveolar lavage fluid. Diagnosis Acute granulomatous interstitial nephritis secondary to diffuse infiltrative lymphocytosis syndrome. Management HAART and prednisone. Diffuse infiltrative lymphocytosis syndrome (DILS) is an autoimmune syndrome characterized by the oligoclonal expansion of CD8+ lymphocytes in response to HIV antigens. Izzedine et al. describe the case of an HIV-infected patient who developed acute granulomatous interstitial nephritis secondary to DILS. The pathogenesis of DILS is unclear, but the clinical spectrum of the disease and its diagnosis and treatment are discussed in detail.

International audience; BackgroundHepatitis C virus (HCV) is the aetiological agent for most cases of cryoglobulinaemia vasculitis. Interferon-containing regimens are associated with important side effects and may exacerbate the vasculitis.ObjectiveTo evaluate safety and efficacy of an oral interferon-free regimen, sofosbuvir plus ribavirin, in HCV-cryoglobulinaemia vasculitis.Patients and methodsWe enrolled 24 consecutive patients (median age of 56.5 years and 46% of women) with HCV-cryoglobulinaemia vasculitis. Sofosbuvir (400 mg/day) was associated with ribavirin (200-1400 mg/day), for 24 weeks. The primary efficacy end point was a complete clinical response of the vasculitis at the end of treatment (week 24).ResultsMain features of HCV-cryoglobulinaemia vasculitis included purpura and peripheral neuropathy (67%), arthralgia (58%), glomerulonephritis (21%) and skin ulcers (12%). Twenty-one patients (87.5%) were complete clinical response at week 24. Complete clinical response was achieved in six (25%) patients at week 4, four (16.6%) at week 8, seven (29.2%) at week 12, three (12.5%) at week 16 and one (4.2%) at week 20. The cryoglobulin level decreased from 0.35 (0.16-0.83) at baseline to 0.15 (0.05-0.45) g/L at week 24. The C4 serum level increased from 0.10 (0.07-0.19) to 0.17 (0.09-0.23) g/L at week 24. Seventy-four per cent of patients had a sustained virological response at week 12 post treatment. The most common side effects were fatigue, insomnia and anaemia. Two serious adverse events were observed.ConclusionsSofosbuvir plus ribavirin combination was associated with a high rate of complete clinical response and a low rate of serious adverse events in HCV-cryoglobulinaemia vasculitis.

Drug-induced kidney injury is a major side effect in clinical practice. Renal injury associated with drugs may involve several components of the kidney: glomerulus, tubules, interstitium, and blood vessels. Acute renal failure may occur as a major reaction to many drugs. Moreover, therapeutic agents may induce an allergic reaction leading to interstitial inflammation and tubular damage. In this article, we present an updated version of the bibliography containing the case reports of nephrotoxicity published in the international literature from January 2003 to December 2005.

Thrombotic microangiopathy (TMA) is a microvascular occlusive disorder characterized by predominantly platelet thrombi in the renal and/or systemic circulations. Haemolytic uraemic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) are the clinical entities comprising TMA, with predominantly renal manifestations in the former, while the latter more often presents with systemic and neurological findings. In some cases, TMA includes de novo hypertension and pulmonary or central nervous system symptoms. TMA is a rare condition, which is severe and may be fatal. Globally, two biological abnormalities explain TMA, namely: ADAMTS13 (A Disintegrin-like And Metalloprotease with ThromboSpondin type 1 repeats) deficiency and various complement component deficiencies. Studies aimed at determining these deficiencies in cases of chemotherapy-induced TMA were not systematically available in the articles reviewed. Gemcitabine was approved by the US Food and Drug Administration (FDA) in 1996 for the treatment of patients with metastatic pancreatic cancer and is currently used for the treatment of a wide range of malignancies, including lymphoma, lung, bladder and breast cancer. Casper et al. [1] first linked TMA to gemcitabine therapy in 1994, during a phase II trial of pancreatic cancer patients receiving this agent. The reported incidence of gemcitabine-associated TMA in the literature is very low, with a manufacturer’s estimate of 0.015% (range 0.008–0.078%) according to adverse event reports in 1997 [2], contrasting with the apparent frequency of patients with gemcitabineassociated TMA at local institutions [3,4]. Since most gemcitabine-treated patients presenting with TMA have far advanced disease and some have received other agents known to be associated with TMA, the exact role of the underlying disease and chemotherapeutic agents is not easily delineated. Although microangiopathy caused by disseminated cancer and chemotherapy-associated TMA may represent two distinct syndromes, and distinguishing clinical and histological features have been identified for these two conditions, there may be more similarities than differences. Nevertheless, clinical improvement after gemcitabine withdrawal in some cases and the result from re-exposure to the drug strongly suggest gemcitabine to be causative for TMA. We report three patients who developed gemcitabine-associated TMA from January 2001 to December 2005, and we undertook a retrospective review to investigate the clinical manifestations and outcomes associated with this condition in case reports and Phase II/III trials.

Blood pressure (BP) varies according to cycles characterized by a reduction during sleep and an increase on awakening. The nighttime decrease is absent or blunted in some patients (termed "non-dippers"). Cross-sectional and prospective data have shown that non-dippers have more target organ damage than have dippers in normotensive and hypertensive subjects. We reviewed the English language literature regarding this association. A non-fortuitous association seems to exist between non-dipper status and cardiovascular risk such as stroke and cardiac events. Among diabetic patients, this phenomenon has been described to occur more often in individuals with autonomic neuropathy and with different degrees of diabetic nephropathy. In normoalbuminuric normotensive type I diabetic patients without any degree of autonomic dysfunction, according to traditional cardiovascular tests, diastolic BP (dBP) night/day ratio is associated with an increased glomerular filtration rate and an increased extracellular volume. The disruption of the circadian rhythm of sympathovagal activity in non-dipper patients was associated with higher levels in systolic BP (sBP) and dBP and with a reduced decline in sBP and dBP levels during the night. Therefore, the prognostic implications of the non-dipper status may be important since the overall 24-h blood pressure load is elevated in these individuals. These data suggest that patients in whom blood pressure decreases during the night incur less damage to their brain, kidneys, heart, and blood vessels than people with elevated nocturnal BP.

BACKGROUND To examine the association between hypertension (HTN), angiotensin system inhibitors (ASI) use and survival outcomes in patients with metastatic renal cell carcinoma (mRCC) treated with sunitinib (SU). METHODS We retrospectively reviewed all patients with mRCC who received SU as first-line treatment in Gustave Roussy from April 2004 to November 2013. The HTN (either pre-existing or secondary to SU), use of ASI (either before or during SU) were analysed. Overall survival (OS) and progression-free survival (PFS) of different exposures were compared with log-rank test. The associations between exposures and survival outcomes were estimated with hazard ratios (HRs) and 95% confidence interval (CI) through a multivariable Cox model adjusted for age, gender, International mRCC Database Consortium risk group and histology. RESULTS Among 213 patients with a 3.6-year median follow-up, 134 were hypertensive and 105 were ASI users with a significant association between the two exposures (P < 0.0001). Hypertensive patients have longer OS (median: 41.6 versus 16.4 months, P < 0.0001) and longer PFS (median: 12.9 versus 5.6 months, P < 0.0001) than non-hypertensive patients (n = 79). ASI users (n = 105) had more HTN_PRE compared with those (n = 108) who did not (65% versus 19%, P < 0.001). Multivariable analysis showed that hypertensive patients were significantly associated with OS (P = 0.05) and marginally with PFS (P = 0.06) while ASI intake was significantly associated with better OS [HR = 0.40; 95% CI (0.24-0.66), P < 0.001] and PFS [HR = 0.55 (0.35-0.86), P = 0.009]. The latter remain statistically significantly associated after controlling for the number of metastases. There is no difference on outcome between patients who receive ASI before starting SU and those who received ASI during SU treatment. CONCLUSION Concomitant use of ASI may significantly improve OS and PFS in mRCC patients receiving SU. HTN is marginally associated with the outcome in these patients.

Resume Le dysfonctionnement renal secondaire a l'administration d'un medicament est une situation frequente dans la pratique clinique. L'atteinte medicamenteuse peut toucher les differentes structures du rein : glomerules, tubules, interstitium, vaisseaux. Le diagnostic de toxicite renale d'un medicament est le plus souvent pose devant une alteration aigue de la filtration glomerulaire, ainsi que devant des manifestations tubulaires et immunoallergiques. La mise a jour annuelle d'une veille bibliographique regroupant les cas de nephrotoxicite rapportes dans la litterature internationale est presentee dans cet article.

Methotrexate (MTX) has become the most commonly prescribed disease-modifying anti-rheumatic drug. However, toxicity is an important drawback of MTX therapy and permanent discontinuation of MTX for adverse effects occurs in 1 patient out of 10. Although high-dose MTX is known to be nephrotoxic, data on low-dose MTX renal effects are scanty. We report an insidious and progressive deterioration of renal function during long-term low-dose MTX in a 59-year-old woman. Kidney biopsy revealed advanced kidney fibrosis with extensive interstitial and glomerular fibrosis, and vascular sclerosis. We suggest that patients on low-dose MTX therapy even alone, should be periodically monitored for creatinine levels.

We report a case of biopsy-proven acute interstitial nephritis (AIN) in a 50-year-old diabetic woman, who had been treated with celecoxib for 4 weeks before presentation. She presented with clinical findings of renal proximal tubulopathy, aseptic leukocyturia and acute renal failure. A kidney biopsy specimen showed AIN with intense tubuli and eosinophilic infiltrate in the interstitium. She recovered normal renal function two weeks after cessation of celecoxib and use of a corticosteroid. A review of the literature yielded eight cases of COX-2 inhibitor-associated AIN with a biopsy-proven diagnosis. Among the reported cases, AIN was diagnosed after an average of 8.3 months of therapy (SD 12 months, range 3 days - 3 years) with 25 mg rofecoxib or 200 mg celecoxib daily. Common symptoms included asthenia, anorexia, nausea and vomiting. The classic triad of fever, rash and eosinophilia was uncommon. Typical laboratory features included hematuria, proteinuria, eosinophilia. Renal failure was common at the time of diagnosis. Mean serum creatinine levels were 0.86 +/- 0.11 mg/dl, 5.66 +/- 3.50 mg/dl and 1.15 +/- 0.24 before treatment, at time of diagnosis and 1 - 2 months after COX-2 inhibitor withdrawal, respectively. Three patients required emergency hemodialysis. After cessation of COX-2 inhibitor treatment, patients recovered completely with a normalized serum creatinine level after one to two months. Management consisted of withdrawal of the COX-2 inhibitor drug and in four patients, corticosteroid therapy was well-tolerated and may have been beneficial.

Le recepteur nucleaire PPARγ est exprime majoritairement dans le tissu adipeux. Neanmoins, il est egalement exprime dans le glomerule renal et les parois vasculaires, contribuant par des mecanismes multiples et complexes, a la sclerose vasculaire et glomerulaire, et ainsi, au developpement de la nephropathie. Des etudes realisees avec les glitazones, agonistes pharmacologiques du recepteur nucleaire PPARγ, dans des modeles experimentaux in vitro, ou in vivo dans des modeles animaux, ont montre que les glitazones avaient des effets favorables sur la pression arterielle et sur la prevention et/ou la progression de la nephropathie diabetique. Les etudes cliniques realisees chez des patients diabetiques de type 2, bien que peu nombreuses, sont egalement en faveur d’un effet benefique des glitazones, sur la pression arterielle et la nephropathie chez ces patients. Il est donc important et justifie de realiser des etudes specifiques chez les patients diabetiques de type 2, visant a etablir et a mieux caracteriser ces effets dans differentes situations cliniques (effet antihypertenseur chez des patients hypertendus selon les classes d’antihypertenseurs associes, prevention et/ou effet sur la progression de la nephropathie diabetique, protection renale, etc.). Les glitazones ont egalement des effets indesirables associes (prise de poids, œdemes peripheriques, retention hydrosodee), qui bien que peu frequents, peuvent en limiter l’emploi chez certains patients. Il est important de mieux etudier ces effets, d’en preciser les mecanismes physiopathologiques et leurs eventuelles consequences a long terme. Il faut enfin souligner la possibilite de manier aisement ces medicaments chez le patient insuffisant renal, sans en modifier la posologie, du fait de leurs proprietes pharmacocinetiques.

Tenofovir disoproxil fumarate (TDF) was developed for the treatment of human immunodeficiency virus (HIV) infection. However, controlled data are sparse on the long-term renal tolerability of TDF at the currently approved daily dose of 300 mg in treatment-naive HIV-infected patients.Over 144 weeks, this 600 patient, multicentre randomized, placebo-controlled, double-blind trial compared stavudine (301 patients) and TDF (299 patients), both administered in combination with lamivudine and efavirenz, in antiretroviral-naive patients. TDF or placebo and stavudine or placebo were administered in an open-label fashion. All medications were taken orally. At screening, all patients had serum creatinines1.5 mg/dl, calculated creatinine clearancesor =60 ml/min and a serum phosphorusor =2.2 mg/dl.The incidences of grades 1 (or =0.5 mg/dl increase from baseline), 2 (2.1-3.0 mg/dl) and 3 (3.1-6.0 mg/dl) serum creatinine elevations at week 144 were 4,1 and 0%, respectively, in the TDF group and 2, 0 and1% in the stavudine control group (P = NS). There were no grade 4 (6 mg/dl) serum creatinine elevations. At week 144, there was no change from baseline in the mean (0.83 mg/dl) serum creatinine in the TDF group compared with a 0.1 mg/dl decrease from baseline (0.83 mg/dl) in the stavudine control group. The incidences of grades 1 (2.0-2.2 mg/dl), 2 (1.5-1.9 mg/dl) and 3 (1.0-1.4 mg/dl) hypophosphataemia at week 144 were 4, 3 and1%, respectively, in the TDF group and 4, 2 and1% in the control group (P = NS). No patient experienced grade 4 (1.0 mg/dl) hypophosphataemia. At week 144, the decrease (Delta) of mean serum phosphorus levels from baseline in both groups was similar (Delta 0.2 from 3.6 mg/dl for the TDF group, and 0.1 from 3.5 mg/dl for the stavudine control group). No patient developed Fanconi's syndrome or proximal renal tubular dysfunction during the study.Through 144 weeks, TDF and stavudine, each administered in combination with efavirenz and lamivudine, had similar renal safety profiles in treatment-naive HIV-infected patients with normal renal function at baseline.

The World Health Organization established official recommendations for managing pain in cancer patients. Since then, this stepladder approach has been widely adopted as a conceptual framework to treat all types of pain. However, those guidelines have not been critically evaluated for use in patients with renal insufficiency. In these patients, the questions of drug dosage adjustment and renal toxicity must be considered. This article reviews the pharmacokinetics of major analgesic drugs and data on their use and/or behavior in renal failure and considers their potential nephrotoxicity. Finally, according to available data in the international literature on pharmacokinetics, recommendations for dosage adjustment in patients with renal failure, and their potential nephrotoxicity, the World Health Organization three-step ladder for the treatment of pain was modified and adapted for patients with impaired renal function. Perspective This well-known treatment strategy now adapted for use in patients with renal insufficiency should secure and rationalize pain treatment in those patients.