RESUMEN

Acute and chronic kidney diseases are an evolving continuum for which reliable biomarkers of early disease are lacking. The potential use of glycosidases, enzymes involved in carbohydrate metabolism, in kidney disease detection has been under investigation since the 1960s. N-acetyl-beta-D-glucosaminidase (NAG) is a glycosidase commonly found in proximal tubule epithelial cells (PTECs). Due to its large molecular weight, plasma-soluble NAG cannot pass the glomerular filtration barrier; thus, increased urinary concentration of NAG (uNAG) may suggest injury to the proximal tubule. As the PTECs are the workhorses of the kidney that perform much of the filtration and reabsorption, they are a common starting point in acute and chronic kidney disease. NAG has previously been researched, and it is widely used as a valuable biomarker in both acute and chronic kidney disease, as well as in patients suffering from diabetes mellitus, heart failure, and other chronic diseases leading to kidney failure. Here, we present an overview of the research pertaining to uNAG's biomarker potential across the spectrum of kidney disease, with an additional emphasis on environmental nephrotoxic substance exposure. In spite of a large body of evidence strongly suggesting connections between uNAG levels and multiple kidney pathologies, focused clinical validation tests and knowledge on underlining molecular mechanisms are largely lacking.

RESUMEN

Chronic kidney disease (CKD) is the progressive loss of renal function. Although advances have been made in understanding the progression of CKD, key molecular events in complex pathophysiological mechanisms that mark each stage of renal failure remain largely unknown. Changes in plasma protein profiles in different disease stages are important for identification of early diagnostic markers and potential therapeutic targets. The goal of this study was to determine the molecular profile of each CKD stage (from 1 to 5), aiming to specifically point out markedly expressed or downregulated proteins. We performed a cross-sectional shotgun-proteomic study of pooled plasma across CKD stages and compared them to healthy controls. After sample pooling and heparin-column purification we analysed proteomes from healthy to CKD stage 1 through 5 participants' plasma by liquid-chromatography/mass-spectrometry. We identified 453 proteins across all study groups. Our results indicate that key events, which may later affect the course of disease progression and the overall pathophysiological background, are most pronounced in CKD stage 2, with an emphasis on inflammation, lipoprotein metabolism, angiogenesis and tissue regeneration. We hypothesize that CKD stage 2 is the tipping point in disease progression and a suitable point in disease course for the development of therapeutic solutions.

RESUMEN

Background: We have previously shown that metzincin protease ADAMTS-4 accompanies renal fibrogenesis, as it appears in the blood of hemodialysis patients. Methods: Native kidney (NKB) and kidney transplant (TXCI) biopsy samples as well as plasma from patients with various stages of CKD were compared to controls. In paired analysis, 15 TXCI samples were compared with their zero-time biopsies (TX0). Tissues were evaluated and scored (interstitial fibrosis and tubular atrophy (IFTA) for NKB and Banff ci for TXCI). Immunohistochemical (IHC) staining for ADAMTS-4 and BMP-1 was performed. Plasma ADAMTS-4 was detected using ELISA. Results: ADAMTS-4 IHC expression was significantly higher in interstitial compartment (INT) of NKB and TXCI group in peritubular capillaries (PTC) and interstitial stroma (INT). Patients with higher stages of interstitial fibrosis (ci > 1 and IFTA > 1) expressed ADAMTS-4 in INT more frequently in both groups (p = 0.005; p = 0.013; respectively). In paired comparison, TXCI samples expressed ADAMTS-4 in INT and PTC more often than TX0. ADAMTS-4 plasma concentration varied significantly across CKD stages, being highest in CKD 2 and 3 compared to other groups (p = 0.0064). Hemodialysis patients had higher concentrations of ADAMTS-4 compared to peritoneal dialysis (p < 0.00001). Conclusion: ADAMTS-4 might have a significant role in CKD as a potential novel diagnostic indicator.

RESUMEN

A 31-year-old woman suffering from diabetes type1 and terminal kidney disease, with simultaneously transplanted kidney and pancreas, developed an episode of acute organ rejection caused by antibodies. The management of organ rejection was complicated by cytomegalovirus viremia, with accompanying leukopenia and neutropenia. The patient also developed invasive aspergillosis of the lungs, which progressed and disseminated hematogenously to the thyroid gland and the skin. Due to resistance to classical antimycotic therapy, the patient was treated with a combination of caspofungin and variconazole. In the beginning of treatment, the effects of this combined therapy were not evident due to strong immunosuppression caused by antimycotic immunoglobulin, which the patient had been administered on her previous hospital stay to treat acute kidney transplant rejection caused by antibodies, as well as due to immunosuppression caused by tacrolimus, mycophenolate mofetil and prednisone. On combined therapy with antimycotic drugs and supportive therapy, the patient was completely cured.

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RESUMEN

Polyomavirus virus associated nephropathy (PVAN) is an important cause of graft failure in the renal transplant population. The prevalence of PVAN has increased from 1% to 10% in the past decade, leading to loss of transplanted organ in 30% to 80% of cases. In the absence of specific antiviral drugs, early detection of disease and modification/reduction of immunosuppressive regimen is currently the cornerstone of therapy. In the setting of multiorgan transplantation, like simultaneous pancreas and kidney transplantation (SPKT), diagnosis and therapy of PVAN can be even more challenging problem. We report a first described case of PVAN in patient after SPKT in Croatia. Patient is a 32 years old Caucasian male with type 1 diabetes mellitus and end stage renal failure, diagnosed for PVAN 6 month after SPKT. Patient was treated with reduced immunosuppressive regimen. At 32 month follow up, patient has preserved kidney and pancreas function with estimated glomerular filtration (eGFR) rate of 91 mL/min and no signs of PVAN on his 2 year protocol kidney biopsy.

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RESUMEN

BK virus associated nephropathy (BKVAN) in transplanted kidney, although recognized as a distinct entity in the 1970-es, continues to represent a challenge in kidney transplantation, mainly because the optimal treatment approach has not been determined yet. The fact that about 10-20% of patients have simultaneously some stage of acute rejection, complicate the treatment even more. Herein we present a case of BK nephropathy in the patient, one year after combined liver and kidney transplantation, complicated by episode of acute T-cell mediated rejection. Identification of decoy cells by cytology urine exam in patient with acute kidney graft function deterioration, raised suspicion of BKVAN. Diagnosis has been made by histological examination and confirmed with immunohistochemical staining for BK virus in kidney graft biopsy. One month after he had been treated for BKVAN with intravenous immunoglobulin, leflunomide and overall immunosuppression therapy reduction, there was further deterioration of graft function due to an episode of acute T-cell mediated rejection (Banff classification IA). He received 500 mg of metilprednisolon intravenously and mycophenolate mofetil had been reintroduced, which resulted in slow partial recovery of the graft function, but never to the baseline values. For the past two years his renal graft function has been stable, maintaining lower levels of immunosuppressive therapy. According to our knowledge this is the first documented case of BK virus associated nephropathy, diagnosed and confirmed with immunohistochemical staining of tissue from kidney biopsy in Croatia.

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