An Innovative Ultrasound Technique for Early Detection of Kidney Dysfunction: Superb Microvascular Imaging as a Reference Standard.

BACKGROUND: Superb microvascular imaging (SMI) is an innovative ultrasound image processing technique that provides greater detail and better visualization of small branching vessels. We assume that SMI will provide sufficient information regarding the severity of chronic kidney disease (CKD) and reflecting histological changes. AIMS: The aims was to assess the capabilities of SMI imaging regarding the early detection of kidney dysfunction and renal fibrosis in comparison to the reference standard renal biopsy for the early diagnosis of kidney fibrosis. METHODS: SMI was performed in patients (n = 52) with CKD stage 2-5, where some of them underwent biopsy proven CKD and fibrosis as part of the diagnosis. In addition, biochemical tests were performed, including kidney function tests, urine collection for proteinuria, and the estimation of GFR by MDRD or CKD-EPI eGFR in CKD patients and healthy controls (n = 17). All subjects underwent SMI, where vascularity is expressed as the SMI index (a low index reflects low vascularity/fibrosis and vice versa). RESULTS: The SMI vascular index was significantly lower in CKD patients as compared with healthy controls (72.2 ± 12.9 vs. 49.9 ± 16.7%, p < 0.01). Notably, a moderate correlation between the SMI index and eGFR was found among the CKD patients (r = 0.56, p < 0.001). Similarly, a strong correlation was found between SCr and the SMI index of the diseased subjects (r = -0.54, p < 0.001). In patients who underwent renal biopsy, the SMI index corresponded with the histological alterations and CKD staging. CONCLUSIONS: This study demonstrated that SMI imaging may be utilized in CKD patients of various stages for the evaluation of chronic renal morphological changes and for differentiation between CKD grades.

Impact of pretreatment with carnitine and tadalafil on contrast-induced nephropathy in CKD patients.

Objective: The present study assesses whether phosphodiesterase type 5 (PDE-5) inhibitor or carnitine exert nephroprotective effects against clinical contrast-induced nephropathy (CIN).Materials and Methods: The present study consisted of three groups of CKD patients. The first group was control group, who were treated with N-acetyl-L-cysteine 1 day before and on the day of radiocontrast administration. The second one was carnitine group, where the patients were infused with carnitine over 10 min 2 h prior to the radiocontrast administration and 24 h post CT. The third one was PDE-5 inhibitor group, where patients were given tadalafil 2 h prior to the administration of the radiocontrast and in the subsequent day. Urine and blood samples were collected before and at the following time sequence: 2, 6, 12, 24, 48, and 120 h after the contrast administration, for creatinine and NGAL determination.Results: Pretreated with N-acetyl-L-cysteine prior to administration of contrast media (CM) to CKD patients caused a significant increase in urinary but not of plasma neutrophil gelatinase-associated lipocalin (NGAL) and serum creatinine (SCr). In contrast, pretreatment with carnitine prevented the increase in urinary NGAL and reduced SCr below basal levels. Similarly, tadalafil administration diminished the elevation of CM-induced urinary NGAL.Conclusions: These results indicate that carnitine and PDE-5 inhibitors may comprise potential therapeutic maneuvers for CIN.

Tumor Lysis Syndrome in Chronic Lymphocytic Leukemia: A Rare Case Report from Nephrology.

BACKGROUND Tumor lysis syndrome is common in hematological malignancy, but less frequent in chronic and solid tumors. Almost always it is observed after chemotherapy or radiotherapy initiation, but rarely occurs spontaneously. CASE REPORT A 89-year-old female with stable chronic lymphocytic leukemia was admitted to the hospital because of worsening dyspnea and dry cough. Her vital signs were normal, except for sinus tachycardia. On physical examination, she appeared distressed, dyspneic, sweaty but afebrile, anxious, but alert and well oriented. Lung examination revealed reduced air entry with bibasilar crackles. No peripheral edema was seen, pulses were normal, and no signs of deep vein thrombosis were observed. Laboratory analysis revealed leukocytosis; but normal hematological and biochemical parameters. Intravenous (IV) furosemide and antibiotics (IV ceftriaxone and orally azithromycin) were started along with steroid therapy (methylprednisolone 62.5 mg, IV). The treatment with steroids lasted for 1 day only, and in the following day, the patient was switched to prednisone (20 mg/day orally) for only 1 additional day. White blood cell count increased on day 1, 2 and 3 after admission, along development of hyperuricemia, hyperphosphatemia, hyperkalemia, acute renal failure and elevated troponin levels. Hemodiafiltration/hemodialysis was initiated, and the patient was discharged after serum concentrations of these electrolytes and kidney function were restored. One month after discharge, the patient denied any malaise and was at stable condition. CONCLUSIONS Herein, we present a case of a patient with stable chronic lymphocytic leukemia, who developed spontaneous tumor lysis syndrome after short low dose of steroid therapy. This case highlights the importance of including spontaneous tumor lysis syndrome in the differential diagnosis of any acute renal failure in the constellation of any malignancy.

Effects of carnitine on oxidative stress response to intravenous iron administration to patients with CKD: impact of haptoglobin phenotype.

BACKGROUND: Anemia is a common disorder in CKD patients. It is largely attributed to decreased erythropoietin (EPO) production and iron deficiency. Therefore, besides EPO, therapy includes iron replenishment. However, the latter induces oxidative stress. Haptoglobin (Hp) protein is the main line of defense against the oxidative effects of Hemoglobin/Iron. There are 3 genotypes: 1-1, 2-1 and 2-2. Hp 2-2 protein is inferior to Hp 1-1 as antioxidant. So far, there is no evidence whether haptoglobin phenotype affects iron-induced oxidative stress in CKD patients. Therefore, the present study examines the influence of carnitine treatment on the intravenous iron administration (IVIR)-induced oxidative stress in CKD patients, and whether Hp phenotype affects this response. TRIAL REGISTRATION: Current Controlled Trials ISRCTN5700858. This study included 26 anemic (Hb = 10.23 ± 0.28) CKD patients (stages 3-4) that were given a weekly IVIR (Sodium ferric gluconate, [125 mg/100 ml] for 8 weeks, and during weeks 5-8 also received Carnitine (20 mg/kg, IV) prior to IVIR. Weekly blood samples were drawn before and after each IVIR for Hp phenotype, C-reactive protein (CRP), advanced oxidative protein products (AOPP), neutrophil gelatinase-associated lipocalin (NGAL), besides complete blood count and biochemical analyses. RESULTS: Eight percent of CKD patients were Hp1-1, 19 % Hp2-1, and 73 % Hp2-2. IVIR for 4 weeks did not increase hemoglobin levels, yet worsened the oxidative burden as was evident by elevated plasma levels of AOPP. The highest increase in AOPP was observed in Hp2-2 patients. Simultaneous administration of Carnitine with IVIR abolished the IVIR-induced oxidative stress as evident by preventing the elevations in AOPP and NGAL, preferentially in patients with Hp2-2 phenotype. CONCLUSIONS: This study demonstrates that Hp2-2 is a significant risk factor for IVIR-induced oxidative stress in CKD patients. Our finding, that co-administration of Carnitine with IVIR preferentially attenuates the adverse consequences of IVIR, suggests a role for Carnitine therapy in these patients.

Maxillary and Frontal Bone Simultaneously Involved in Brown Tumor due to Secondary Hyperparathyroidism in a Hemodialysis Patient.

Brown tumors are rare focal giant cell lesions of the bone caused by primary hyperparathyroidism (HPT). Brown tumor was reported in 1891; it presents as the end-stage findings of HPT. Common involvements are skull and pelvic girdle. We describe a case of 46-year-old female hemodialysis patient, with secondary HPT in whom multiple masses lesions of the left maxillary sinus and frontal bone were radiologically suspected to be brown tumor. This unusual manifestation of secondary HPT can be expected to occur with increased longevity of patients with renal failure and illustrates the need to include brown tumor in the differential diagnosis.

Phosphodiesterase-5 inhibition attenuates early renal ischemia-reperfusion-induced acute kidney injury: assessment by quantitative measurement of urinary NGAL and KIM-1.

Acute kidney injury (AKI) is a common clinical problem that still lacks effective treatment. Phosphodiesterase-5 (PDE5) inhibitors possess anti-apoptotic and anti-oxidant properties, making it a promising therapy for ischemia-reperfusion (I/R) injury of various organs. The present study evaluated the early nephroprotective effects of Tadalafil, a PDE5 inhibitor, in an experimental model of renal I/R. Sprague-Dawley rats were divided into two groups: vehicle-treated I/R (n = 10), and Tadalafil (10 mg/kg po)-treated I/R group (n = 11). After removal of the right kidney and collection of two baseline urine samples, the left renal artery was clamped for 45 min followed by reperfusion for 60, 120, 180, and 240 min. Functional and histological parameters of the kidneys from the various groups were determined. In the vehicle-treated I/R group, glomerular filtration rate was significantly reduced compared with that in normal kidneys. In addition, the ischemic kidney showed remarkable cast formation, necrosis, and congestion, a consistent pattern of acute tubular necrosis. Furthermore, urinary excretion of NGAL and KIM-1, two novel biomarkers of kidney injury, substantially increased following I/R insult. In contrast, Tadalafil treatment resulted in a significant improvement in kidney function and amelioration of the adverse histological alterations of the ischemic kidney. Noteworthy, the urinary excretion of NGAL and KIM-1 markedly decreased in the Tadalafil-treated I/R group. These findings demonstrate that Tadalafil possesses early nephroprotective effects in rat kidneys subjected to I/R insult. This approach may suggest a prophylactic therapy for patients with ischemic AKI.

[Neutrophil gelatinase-associated lipocalin (NAGL): a novel biomarker for acute kidney injury].

The incidence of both acute and chronic kidney diseases is persistently increasing and is reaching epidemic proportions. Early therapeutic intervention may significantly decrease the morbidity and mortality rates among these patients. However, the lack of early non-invasive biomarkers has hampered our ability to diagnose kidney diseases as early as possible, and subsequently, to initiate timely, effective, and appropriate treatment. Until recently, no biomarker for kidney disease, except for creatinine was available to clinicians in general and nephrologists in particular. Unfortunately, creatinine is an unreliable indicator during acute and chronic changes in kidney function, since serum creatinine concentrations can vary widely with age, gender, muscle mass, muscle metabolism, medications and hydration status. Secondly, serum creatinine concentrations may not change until a significant amount of kidney function (50-60%) has already been lost. In the last few years various specific biomarkers for kidney diseases were discovered and the most reliable representative is neutrophil gelatinase-associated lipocalin (NGAL), which is the focus of this review. Several studies have demonstrated that plasma and urinary NGAL levels increase two hours after the induction of acute kidney injury (AKI) in several clinical situations such as cardiac surgery, radiocontrast nephropathy, kidney transplantation, hemolytic uremic syndrome and critically ill patients in intensive care unit. Serum and urine concentrations of NGAL increase before those of creatinine, making this biomarker a powerful tool for early detection of renal disease, thus hopefully to reduce the high mortality rate among patients with AKI.