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The qualitative evaluation of proteinuria represents a crucial diagnostic step in clinical practice for the classification of renal diseases according to glomerular, tubulo-interstitial, mixed injury or related to monoclonal gammopathy. Combined with the quantitative evaluation, it also allows an assessment of the disease's severity and prognosis as well as the response to treatment. The development of the urine protein profile (UPP) combines specific urine protein assays on a urine spot analyzing glomerular protein markers such as albumin, transferrin and immunoglobulin G, and tubular markers such as alpha-1microglobulin and retinol binding protein, to generate a detailed quantitative and qualitative proteinuria assessment. This short overview proposes to illustrate the diagnostic and prognostic usefulness of UPP in different common clinical situations., (Copyright © 2019 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Tenofovir disoproxil fumarate (TDF) is a commonly used antiretroviral drug for HIV, rarely causing Fanconi syndrome and acute kidney injury. We retrospectively analyzed the clinico pathological presentation of 20 cases of tenofovir-induced tubulopathy, and investigated the renal expression of the megalin and cubilin proteins, as well as the mitochondrial respiratory chain activity. Estimated glomerular filtration rate (eGFR) before TDF exposure was 92 ml/min/1.73m 2 , decreasing to 27.5 ml/min/1.73m 2 at the time of biopsy, with 30% of patients requiring renal replacement therapy. Proximal tubular expression of megalin and cubilin was altered in 19 and 18 cases, respectively, whereas it was preserved in patients exposed to TDF without proximal tubular dysfunction and in HIV-negative patients with acute tubular necrosis. Loss of megalin/cubilin was correlated with low eGFR and high urine retinol binding protein at the time of biopsy, low eGFR at last follow-up, and was more severe in patients with multifactorial toxicity. Patients with additional nephrotoxic conditions promoting tenofovir accumulation showed a lower eGFR at presentation and at last follow-up, and more severe lesions of acute tubular necrosis, than those with isolated tenofovir toxicity. Altered mitochondrial COX activity in proximal tubules was observed and may be an early cellular alteration in tenofovir nephrotoxicity. In conclusion, altered megalin/cubilin expression represents a distinctive feature in tenofovir-induced tubulopathy, and its severity is correlated with urine retinol binding protein loss and is associated with a poor renal prognosis. Concomitant exposure to other nephrotoxic conditions severely impacts the renal presentation and outcome., (Copyright © 2018. Published by Elsevier Inc.)

There is a need for multiplex, specific and quantitative methods to speed-up the development of acute kidney injury biomarkers and allow a more specific diagnosis. Targeted proteomic analysis combined with stable isotope dilution has recently emerged as a powerful option for the parallelized evaluation of candidate biomarkers. This article presents the development of a targeted proteomic assay to quantify 4 acute kidney injury biomarker candidates in urine samples. The proteins included in the assessed panel consisted of myo-inositol oxygenase (MIOX), phosphoenolpyruvate carboxykinase 1 (PCK1), neutrophil gelatinase-associated lipocalin (NGAL) and liver fatty acid-binding protein (L-FABP). The proteomic assay combined an antibody-free sample preparation and a liquid chromatography-selected reaction monitoring (LC-SRM) analysis pipeline. For accurate quantification of the selected candidates, we used PSAQ (Protein Standard Absolute Quantification) standards which are isotopically labeled versions of the target proteins. When added directly to the biological samples, these standards improve detection specificity and quantification accuracy. The multiplexed assay developed for the 4 biomarker candidates showed excellent analytical performance, in line with the recommendations of health authorities. Tests on urine from two small patient cohorts and a group of healthy donors confirmed the relevance of NGAL and L-FABP as biomarkers for AKI diagnosis. The assay is readily adaptable to other biomarker candidates and should be very useful for the simultaneous and accurate quantification of multiple biomarkers., (Copyright © 2016 Elsevier B.V. All rights reserved.)

There is little data availableon the nephrotoxicity of pemetrexed, a new generation antifolate agent that is increasingly used in the treatment of numerous malignant tumors. We report the observation of two patients suffering from non-small cell lung cancer who developed acute kidney injury (AKI) after administration of pemetrexed. In one case, pemetrexed was used as a single agent treatment. In the other, pemetrexed was first co-administered with cisplatin, then alone, with AKI worsening 2 months after the discontinuation of cisplatin. The two patients concomitantly developed edema of the face, which is a rare adverse side effect of pemetrexed. Renal biopsies showed acute tubular necrosis and interstitial fibrosis. In both cases, chronic kidney disease (CKD) persisted despite drug discontinuation. Herein, we discuss renal presentation, risk factors, and prognosis of pemetrexed-induced nephrotoxicity.

The scleroderma renal crisis is characterized by acute onset of severe hypertension and by rapidly progressive hyperreninemic renal failure. There is, however, a very limited subset of patients with rapidly progressive renal failure who remain normotensive and develop ANCA-positive crescentic glomerulonephritis. We report a case of normotensive acute renal failure secondary to anti-MPO antibody-associated crescentic glomerulonephritis in a patient with diffuse systemic sclerosis. She was referred to our department with normal blood pressure and no extrarenal clinical manifestation ofvasculitis. She presented with rapidly progressive renal failure, microscopic hematuria and minimal proteinuria. P-ANCA were positive by immunofluorescence, with ELISA-confirmed specificity for myeloperoxidase. Renal biopsy revealed typical features of pauciimmune glomerulonephritis with crescent formation and fibrinoid necrosis. The patient was initially treated with i.v. cyclophosphamide only. Because of ongoing deteriorating renal function, additional treatment with intravenous pulses of methylprednisolone followed by oral prednisone was started and allowed renal function improvement. After 9 months, serum creatinine had almost returned to normal level with minimal proteinuria, no hematuria and negative ANCA testing. Control kidney biopsy only revealed scar lesions. The association of ANCA-positive crescentic glomerulonephritis and systemic sclerosis is a very rare event. Treatment with intravenous cyclophosphamide and corticosteroids allows rapid and long-term improvement of renal function. The onset of typical scleroderma renal crisis triggered by high-dose corticosteroids is unlikely but requires a close follow-up of patients with overlapping systemic sclerosis. Diagnosis and treatment are discussed and previously published cases are reviewed.

Background: A 30-year-old HIV-infected woman presented with fever and abdominal pain 4 days after initiation of highly active antiretroviral therapy (HAART), and 1 month after initiation of antimicrobial therapy for Mycobacterium tuberculosis infection. A diagnosis of immune restoration inflammatory syndrome (IRIS) was considered, and corticosteroids were started. Steroid therapy doses were progressively tapered, during which time the patient developed renal failure with enlarged kidneys. A renal biopsy showed acute interstitial nephritis. Extensive investigations failed to detect active infection. The efficacy of HAART was attested by increased CD4+ cell counts and undetectable viral replication., Investigations: Physical examination, plasma viral load and CD4+ cell count, abdominal and renal ultrasound, renal and peritoneal biopsies, renal and liver function, chest X-ray, and bronchoalveolar lavage culture., Diagnosis: Acute renal failure secondary to IRIS., Management: Prednisone therapy.