Acute renal failure induced by acute interstitial nephritis secondary to cocaine

Document publicat també en castellàCocaine has been used by 2.6% of the Spanish population aged between 15 and 64 at some point in their life, making it one of the most consumed illegal drugs after cannabis.1 Cocaine use is associated with multiple complications: neurological, cardiovascular, psychiatric, pulmonary, gastrointestinal and nephrological. Renal complications associated with cocaine use have received little attention, despite the existence of several mechanisms, in addition to secondary high blood pressure, that can cause acute renal failure (ARF) or worsen a pre-existing case of chronic renal failure. Drug-induced acute interstitial nephritis (DIAIN) represents a high percentage of acute renal failure in clinical practice. Some studies indicate that DIAIN is the lesion responsible for renal failure in about 15% of biopsies with ARF. Furthermore, in many cases of DIAIN, no biopsy is performed and diagnosis is based on clinical data and recent administration of a new drug which, as described below, is sometimes not very easy to identify

Proteomic Characterization of Urinary Extracellular Vesicles from Kidney-Transplanted Patients Treated with Calcineurin Inhibitors

Use of immunosuppressive drugs is still unavoidable in kidney-transplanted patients. Since their discovery, calcineurin inhibitors (CNI) have been considered the first-line immunosuppressive agents, in spite of their known nephrotoxicity. Chronic CNI toxicity (CNIT) may lead to kidney fibrosis, a threatening scenario for graft survival. However, there is still controversy regarding CNIT diagnosis, monitoring and therapeutic management, and their specific effects at the molecular level are not fully known. Aiming to better characterize CNIT patients, in the present study, we collected urine from kidney-transplanted patients treated with CNI who (i) had a normal kidney function, (ii) suffered CNIT, or (iii) presented interstitial fibrosis and tubular atrophy (IFTA). Urinary extracellular vesicles (uEV) were enriched and the proteome was analyzed to get insight into changes happening during CNI. Members of the uroplakin and plakin families were significantly upregulated in the CNIT group, suggesting an important role in CNIT processes. Although biomarkers cannot be asserted from this single pilot study, our results evidence the potential of uEV as a source of non-invasive protein biomarkers for a better detection and monitoring of this renal alteration in kidney-transplanted patients

Proteomic Characterization of Urinary Extracellular Vesicles from Kidney-Transplanted Patients Treated with Calcineurin Inhibitors

Use of immunosuppressive drugs is still unavoidable in kidney-transplanted patients. Since their discovery, calcineurin inhibitors (CNI) have been considered the first-line immunosuppressive agents, in spite of their known nephrotoxicity. Chronic CNI toxicity (CNIT) may lead to kidney fibrosis, a threatening scenario for graft survival. However, there is still controversy regarding CNIT diagnosis, monitoring and therapeutic management, and their specific effects at the molecular level are not fully known. Aiming to better characterize CNIT patients, in the present study, we collected urine from kidney-transplanted patients treated with CNI who (i) had a normal kidney function, (ii) suffered CNIT, or (iii) presented interstitial fibrosis and tubular atrophy (IFTA). Urinary extracellular vesicles (uEV) were enriched and the proteome was analyzed to get insight into changes happening during CNI. Members of the uroplakin and plakin families were significantly upregulated in the CNIT group, suggesting an important role in CNIT processes. Although biomarkers cannot be asserted from this single pilot study, our results evidence the potential of uEV as a source of non-invasive protein biomarkers for a better detection and monitoring of this renal alteration in kidney-transplanted patients

Acute renal failure induced by acute interstitial nephritis secondary to cocaine

Document publicat també en castellàCocaine has been used by 2.6% of the Spanish population aged between 15 and 64 at some point in their life, making it one of the most consumed illegal drugs after cannabis.1 Cocaine use is associated with multiple complications: neurological, cardiovascular, psychiatric, pulmonary, gastrointestinal and nephrological. Renal complications associated with cocaine use have received little attention, despite the existence of several mechanisms, in addition to secondary high blood pressure, that can cause acute renal failure (ARF) or worsen a pre-existing case of chronic renal failure. Drug-induced acute interstitial nephritis (DIAIN) represents a high percentage of acute renal failure in clinical practice. Some studies indicate that DIAIN is the lesion responsible for renal failure in about 15% of biopsies with ARF. Furthermore, in many cases of DIAIN, no biopsy is performed and diagnosis is based on clinical data and recent administration of a new drug which, as described below, is sometimes not very easy to identify

Acute renal failure induced by acute interstitial nephritis secondary to cocaine

Document publicat també en castellàCocaine has been used by 2.6% of the Spanish population aged between 15 and 64 at some point in their life, making it one of the most consumed illegal drugs after cannabis.1 Cocaine use is associated with multiple complications: neurological, cardiovascular, psychiatric, pulmonary, gastrointestinal and nephrological. Renal complications associated with cocaine use have received little attention, despite the existence of several mechanisms, in addition to secondary high blood pressure, that can cause acute renal failure (ARF) or worsen a pre-existing case of chronic renal failure. Drug-induced acute interstitial nephritis (DIAIN) represents a high percentage of acute renal failure in clinical practice. Some studies indicate that DIAIN is the lesion responsible for renal failure in about 15% of biopsies with ARF. Furthermore, in many cases of DIAIN, no biopsy is performed and diagnosis is based on clinical data and recent administration of a new drug which, as described below, is sometimes not very easy to identify

Urinary vitronectin identifies patients with high levels of fibrosis in kidney grafts

Altres ajuts: The project leading to these results has also received funding from "la Caixa" Foundation (ID 100010434), under agreement CI19-00048. This activity has received funding from the European Institute of Innovation and Technology (EIT). This body of the European Union receives support from the European Union's Horizon 2020 research and innovation program. LCP is sponsored by the Spanish Government FPU grant ("Formación de Personal Universitario", FPU17/01444). MF is supported by ISCIII (MS19/00018), co-funded by ERDF/ESF, "Investing in your future". FEB is a researcher from Fundació Institut de Recerca en Ciències de la Salut Germans Trias i Pujol, supported by the Health Department of the Catalan Government (Direcció General de Recerca i Innovació, Dept. Salut, Generalitat de Catalunya).In kidney transplantation, fibrosis represents the final and irreversible consequence of the pathogenic mechanisms that lead to graft failure, and in the late stages it irremediably precedes the loss of renal function. The invasiveness of kidney biopsy prevents this condition from being frequently monitored, while clinical data are rather unspecific. The objective of this study was to find noninvasive biomarkers of kidney rejection. We carried out proteomic analysis of the urinary Extracellular Vesicles (uEVs) from a cohort of kidney transplant recipients (n = 23) classified according to their biopsy-based diagnosis and clinical parameters as interstitial fibrosis and tubular atrophy (IFTA), acute cellular rejection (ACR), calcineurin inhibitors toxicity (CNIT) and normal kidney function (NKF). Shotgun mass spectrometry of uEV-proteins identified differential expression of several proteins among these different groups. Up to 23 of these proteins were re-evaluated using targeted proteomics in a new independent cohort of patients (n = 41) classified in the same diagnostic groups. Among other results, we found a differential expression of vitronectin (VTN) in patients displaying chronic interstitial and tubular lesions (ci and ct mean > 2 according to Banff criteria). These results were further confirmed by a pilot study using enzyme-linked immunosorbent assay (ELISA). Urinary vitronectin levels are a potential stand-alone biomarker to monitor fibrotic changes in kidney transplant recipients in a non-invasive fashion. The online version of this article (10.1007/s40620-020-00886-y) contains supplementary material, which is available to authorized users

A randomized study comparing parathyroidectomy with cinacalcet for treating hypercalcemia in kidney allograft recipients with hyperparathyroidism

Tertiary hyperparathyroidism is a common cause of hypercalcemia after kidney transplant. We designed this 12-month, prospective, multicenter, open-label, randomized study to evaluate whether subtotal parathyroidectomy is more effective than cinacalcet for controlling hypercalcemia caused by persistent hyperparathyroidism after kidney transplant. Kidney allograft recipients with hypercalcemia and elevated intact parathyroid hormone (iPTH) concentration were eligible if they had received a transplant ≥6 months before the study and had an eGFR>30 ml/min per 1.73 m2. The primary end point was the proportion of patients with normocalcemia at 12 months. Secondary end points were serum iPTH concentration, serum phosphate concentration, bone mineral density, vascular calcification, renal function, patient and graft survival, and economic cost. In total, 30 patients were randomized to receive cinacalcet (n=15) or subtotal parathyroidectomy (n=15). At 12 months, ten of 15 patients in the cinacalcet group and 15 of 15 patients in the parathyroidectomy group (P=0.04) achieved normocalcemia. Normalization of serum phosphate concentration occurred in almost all patients. Subtotal parathyroidectomy induced greater reduction of iPTH and associated with a significant increase in femoral neck bone mineral density; vascular calcification remained unchanged in both groups. The most frequent adverse events were digestive intolerance in the cinacalcet group and hypocalcemia in the parathyroidectomy group. Surgery would be more cost effective than cinacalcet if cinacalcet duration reached 14 months. All patients were alive with a functioning graft at the end of follow-up. In conclusion, subtotal parathyroidectomy was superior to cinacalcet in controlling hypercalcemia in these patients with kidney transplants and persistent hyperparathyroidism

A randomized study comparing parathyroidectomy with cinacalcet for treating hypercalcemia in kidney allograft recipients with hyperparathyroidism

Tertiary hyperparathyroidism is a common cause of hypercalcemia after kidney transplant. We designed this 12-month, prospective, multicenter, open-label, randomized study to evaluate whether subtotal parathyroidectomy is more effective than cinacalcet for controlling hypercalcemia caused by persistent hyperparathyroidism after kidney transplant. Kidney allograft recipients with hypercalcemia and elevated intact parathyroid hormone (iPTH) concentration were eligible if they had received a transplant ≥6 months before the study and had an eGFR>30 ml/min per 1.73 m2. The primary end point was the proportion of patients with normocalcemia at 12 months. Secondary end points were serum iPTH concentration, serum phosphate concentration, bone mineral density, vascular calcification, renal function, patient and graft survival, and economic cost. In total, 30 patients were randomized to receive cinacalcet (n=15) or subtotal parathyroidectomy (n=15). At 12 months, ten of 15 patients in the cinacalcet group and 15 of 15 patients in the parathyroidectomy group (P=0.04) achieved normocalcemia. Normalization of serum phosphate concentration occurred in almost all patients. Subtotal parathyroidectomy induced greater reduction of iPTH and associated with a significant increase in femoral neck bone mineral density; vascular calcification remained unchanged in both groups. The most frequent adverse events were digestive intolerance in the cinacalcet group and hypocalcemia in the parathyroidectomy group. Surgery would be more cost effective than cinacalcet if cinacalcet duration reached 14 months. All patients were alive with a functioning graft at the end of follow-up. In conclusion, subtotal parathyroidectomy was superior to cinacalcet in controlling hypercalcemia in these patients with kidney transplants and persistent hyperparathyroidism