Elerson Carlos Costalonga

The potential role of C-reactive protein in distinguishing cytomegalovirus from tuberculosis and bacterial infections in renal transplant recipients

Abstract:  Introduction:  The delay in the diagnosis of infections can be deleterious in renal transplant recipients. Thus, laboratory tests leading to an earlier diagnosis are very useful for these patients.

Valproic Acid Prevents Renal Dysfunction and Inflammation in the Ischemia-Reperfusion Injury Model

Ischemia-reperfusion injury (IRI) is a major contributor to acute kidney injury (AKI). At present, there are no effective therapies to prevent AKI. The aim of this study was to analyse whether valproic acid (VPA), a histone deacetylase inhibitor with anti-inflammatory properties, prevents renal IRI. Male Wistar rats were divided into three groups: SHAM rats were subjected to a SHAM surgery, IRI rats underwent bilateral renal ischemia for 45 min, and IRI + VPA rats were treated with VPA at 300 mg/kg twice daily 2 days before bilateral IRI. Animals were euthanized at 48 hours after IRI. VPA attenuated renal dysfunction after ischemia, which was characterized by a decrease in BUN (mg/dL), serum creatinine (mg/dL), and FENa (%) in the IRI + VPA group (39 ± 11, 0.5 ± 0.05, and 0.5 ± 0.06, resp.) compared with the IRI group (145 ± 35, 2.7 ± 0.05, and 4.9 ± 1, resp.; p < 0.001). Additionally, significantly lower acute tubular necrosis grade and number of apoptotic cells were found in the IRI + VPA group compared to the IRI group (p < 0.001). Furthermore, VPA treatment reduced inflammatory cellular infiltration and expression of proinflammatory cytokines. These data suggest that VPA prevents the renal dysfunction and inflammation that is associated with renal IRI.

Prostatic surgery associated acute kidney injury

Acute kidney injury (AKI) is associated with extended hospital stays, high risks of in-hospital and long-term mortality, and increased risk of incident and progressive chronic kidney disease. Patients with urological diseases are a high-risk group for AKI owing to the coexistence of obstructive uropathy, older age, and preexistent chronic kidney disease. Nonetheless, precise data on the incidence and outcomes of postoperative AKI in urological procedures are lacking. Benign prostatic hyperplasia and prostate cancer are common diagnoses in older men and are frequently treated with surgical procedures. Whereas severe AKI after prostate surgery in general appears to be unusual, AKI associated with transurethral resection of the prostate (TURP) syndrome and with rhabdomyolysis (RM) after radical prostatectomy have been frequently described. The purpose of this review is to discuss the current knowledge regarding the epidemiology, risk factors, outcomes, prevention, and treatment of AKI associated with prostatic surgery. The mechanisms of TURP syndrome and RM following prostatic surgeries will be emphasized.

Evaluation of Intermittent Hemodialysis in Critically Ill Cancer Patients with Acute Kidney Injury Using Single-Pass Batch Equipment

Background Data on renal replacement therapy (RRT) in cancer patients with acute kidney injury (AKI) in the intensive care unit (ICU) is scarce. The aim of this study was to assess the safety and the adequacy of intermittent hemodialysis (IHD) in critically ill cancer patients with AKI. Methods and Findings In this observational prospective cohort study, 149 ICU cancer patients with AKI were treated with 448 single-pass batch IHD procedures and evaluated from June 2010 to June 2012. Primary outcomes were IHD complications (hypotension and clotting) and adequacy. A multiple logistic regression was performed in order to identify factors associated with IHD complications (hypotension and clotting). Patients were 62.2 ± 14.3 years old, 86.6% had a solid cancer, sepsis was the main AKI cause (51%) and in-hospital mortality was 59.7%. RRT session time was 240 (180–300) min, blood/dialysate flow was 250 (200–300) mL/min and UF was 1000 (0–2000) ml. Hypotension occurred in 25% of the sessions. Independent risk factors (RF) for hypotension were dialysate conductivity (each ms/cm, OR 0.81, CI 0.69–0.95), initial mean arterial pressure (each 10 mmHg, OR 0.49, CI 0.40–0.61) and SOFA score (OR 1.16, CI 1.03–1.30). Clotting and malfunctioning catheters (MC) occurred in 23.8% and 29.2% of the procedures, respectively. Independent RF for clotting were heparin use (OR 0.57, CI 0.33–0.99), MC (OR 3.59, CI 2.24–5.77) and RRT system pressure increase over 25% (OR 2.15, CI 1.61–4.17). Post RRT blood tests were urea 71 (49–104) mg/dL, creatinine 2.71 (2.10–3.8) mg/dL, bicarbonate 24.1 (22.5–25.5) mEq/L and K 3.8 (3.5–4.1) mEq/L. Conclusion IHD for critically ill patients with cancer and AKI offered acceptable hemodynamic stability and provided adequate metabolic control.

Three cases of hypertension and Renal Arteriovenous fistula with a de novo fistula

Fistula Arteriovenosa Renal (FAVR) e uma causa rara e potencialmente reversivel de hipertensao e insuficiencia renal e/ou cardiaca. O tratamento da FAVR visa preservar o maximo de parenquima renal e, concomitantemente, erradicar os sintomas e efeitos hemodinâmicos decorrentes da FAVR. No presente estudo, serao relatados tres casos de FAVR, incluindo um caso de FAVR idiopatica de novo, que se apresentaram com hipertensao e insuficiencia renal e/ou cardiaca, e descrever a terapeutica adotada e os resultados obtidos.The Renal Arteriovenous Fistula (RAVF) is a rare and potentially reversible cause of hypertension and kidney and/or heart failure. The treatment of RAVF aims at preserving the most of the renal parenchyma and, concomitantly, eradicating the symptoms and hemodynamic effects caused by the RAVF. The present study reports three cases of RAVF, including one case of a de novo idiopathic RAVF, which presented with hypertension and kidney and/or heart failure and describes the therapeutic measures used to treat these patients as well as the outcomes.

Assessment of Kidney Function in Patients With Cancer

Cancer patients are living longer. The sequelae of cancer treatment and the role of comorbid conditions present before the diagnosis, such as CKD, have been increasingly recognized. The interface between CKD and cancer is multifaceted. CKD is frequently observed in patients with cancer, and cancer treatment contributes to CKD development and progression. In addition, CKD has been recognized as an important risk factor for cancer development and reduced specific cancer survival. In this context, an accurate evaluation of the glomerular filtration rate (GFR) during oncologic treatment is pivotal and is used to define surgery strategies, program prophylactic management of contrasted examinations, make decisions on cisplatin eligibility, and adjust drug prescriptions, particularly chemotherapy agents. Although the most commonly used equations to estimate GFR based on serum creatinine levels in clinical practice (Cockcroft-Gault, Modification of Diet in Renal Disease Study, and CKD Epidemiology Collaboration equations) have not been validated in patients with cancer in large prospective studies, there is increasingly evidence supporting the use of CKD Epidemiology Collaboration equation to assess the GFR in patients with cancer, including for the use of chemotherapy prescriptions. Many patients with cancer may have changes in nutrition status and clearance measurements such as exogenous filtration markers might be extremely useful when clinical decisions differ depending on the GFR level. Future perspectives include the advent of new serum GFR biomarkers such as cystatin C, beta-trace protein, and beta-2 microglobulin as well as the GFR assessment by measuring total kidney parenchymal volume through image examinations.

Drug-Induced Acute Kidney Injury

Abstract The epidemiology of acute kidney injury (AKI) has changed remarkably over the last few decades. Currently a majority of affected patients are critically ill older individuals hospitalized in an intensive care unit (ICU) with comorbidities and multiple organ failure. In the ICU, either nephrotoxicity alone or, most commonly, associated with ischemia, has been a relevant related factor in the pathogenesis of AKI in almost half of the cases. Virtually all mechanisms or processes potentially leading to renal injury have been associated with drug nephrotoxicity: acute tubular cell injury, changes in renal hemodynamics, intratubular obstruction, acute interstitial nephritis, hypersensitivity vasculitis, thrombotic microangiopathy, osmotic nephrosis, and rhabdomyolysis. Measurement of serum creatinine always should be performed before administration of potentially nephrotoxic drugs, and even small increments in creatinine are an independent risk factor for increased mortality in hospitalized patients. The use of a nonnephrotoxic drug must be considered for patients at higher risk for renal injury. Patients must be adequately hydrated and sodium repleted before receiving a nephrotoxic drug. The concomitant use of two or more different nephrotoxic drugs must be avoided. Drug dosage should be adjusted in accordance with organ functional status, distribution volume, and drug pharmacokinetics. It always should be checked if a nephrotoxic drug had specific measures to prevent or attenuate its potential for renal damage. Currently, numerous drugs have been related to development of AKI. Of the vast array of drugs with potential for nephrotoxicity, those more frequently prescribed for patients in the ICU are discussed in this chapter: antiinfective agents (aminoglycosides, vancomycin, amphotericin B, polymyxins, highly active antiretroviral therapy [HAART]), contrast agents, NSAIDs, and drugs blocking the renin-angiotensin-aldosterone system (ACEI, ARB, and renin inhibitors).

Renal infiltration presenting as acute kidney injury in Hodgkin lymphoma – A case report and review of the literature

Renal involvement in Hodgkin lymphoma (HL) is rare, although extralymphatic disease is usually found. Acute kidney injury is a recognized presentation of non-Hodgkin lymphoma, with bilateral kidney involvement, promptly requiring specific treatment. Regarding to HL, this manifestation is extremely rare and lacks pathologic description and management experiences. Herein, we describe a case of HL with atypical presentation as well as its management, current evaluation by PET-scan and histologic findings. This case report highlights clinical presentation and a successful experience on managing these cases. Moreover, it is important to drive biologic insights for understanding of kidney infiltration mechanism in HL.

Use of regional citrate anticoagulation for continuous venovenous hemodialysis in critically ill cancer patients with acute kidney injury

Purpose: This study aimed to evaluate the safety and efficacy of a regional citrate anticoagulation (RCA) protocol for continuous venovenous hemodialysis (CVVHD) in cancer patients with acute kidney injury (AKI) in the intensive care unit (ICU) setting. Material and methods: One hundred twenty two consecutive ICU cancer patients with AKI treated with citrate‐based CVVHD were prospectively evaluated in this prospective observational study. Results: A total of 7198 h of CVVHD therapy (250 filters) were performed. Patients were 61.3 ± 15.7 years old, 78% had solid cancer and the main AKI cause was sepsis (50%). The in‐hospital mortality was 78.7%. Systemic ionized calcium (SCai) was 4.35 (4.10–4.60) mg/dL, severe hypocalcemia (SCai <3.6 mg/dL) was observed in 4.3% of procedures and post‐filter ionized calcium was 1.60 (1.40–1.80) mg/dL. Median filter patency was 24.8 (11–43) hours. Factors related to filter clotting were: no tumor evidence (OR 0.44, CI 0.18–0.99); genitourinary tumor (OR 1.83, CI 1.18–2.81); platelets number (each 10,000/mm3) (OR 1.02, CI 1.00–1.04); International Normatized Ratio (INR) (OR 0.59, CI 0.41–0.85) and citrate dose (each 10 mL/h) (OR 0.88, CI 0.82–0.95). Conclusion: Filter patency was relatively short and clotting was associated with active cancer disease, genitourinary tumor, lower citrate dose and lower INR. HighlightsRegional citrate anticoagulation was safe and associated with adequated metabolic control.The incidence of electrolytic and acid‐base disorders was similar to that observed in non cancer patients.Filter patency was relatively short 24.8 (11 – 43) hours.Factors related to filter clotting were, genitourinary tumor, platelets number and citrate dose.

Anti-fibrotic effects of valproic acid in experimental peritoneal fibrosis

Background Progressive fibrous thickening of the peritoneal membrane is a complication of long-term peritoneal dialysis (PD). TGF-β/Smad pathway activation, inflammation, and neoangiogenesis play important roles in peritoneal membrane (PM) changes induced by PD. Recently, histone deacetilase inhibitors (HDACi) have shown anti-fibrotic and anti-inflammatory effects in different experimental models. These drugs prevent deacetylation of histones causing a loosen chromatin, which in turn induce the expression of some anti-fibrotic genes. In addition, acetylation may increase the activity of proteins involved in tissue fibrosis, such as Smad7. Here, we explored the effect of valproic acid (VPA), an HDACi, on the development of peritoneal fibrosis (PF) in rats. Methods PF was induced by daily intraperitoneal injections of 0.1% chlorhexidine gluconate (CG) for 15 consecutive days. Male Wistar rats (250–300 g) were divided into 3 groups: CONTROL, control rats receiving only vehicle; PF, peritoneal fibrosis induced in rats; PF+VPA, rats with PF treated with VPA (300 mg/kg/day by gavage). PF was assessed by Masson’s trichrome staining. Inflammation and fibrosis-associated factors were assessed by immunohistochemistry, immunofluorescence, multiplex analysis, and qPCR. Results Treatment with VPA significantly reduced PM thickness and the expression of myofibroblasts, besides preventing loss of ultrafiltration capacity of the PM. The upregulation of profibrotic factors (TGF-β, fibronectin, and Smad3) in the PF group was significantly ameliorated by VPA. VPA modulated the TGF/Smad pathway, inhibiting phosphorylated Smad3 expression and inducing an increased Smad7 expression in the FP+VPA group. The neoangiogenesis and the expression of proinflammatory cytokines (TNF-α, IL-1β, MCP-1) observed in the PF group was significantly reduced by VPA. Conclusions Our results indicate that VPA suppressed experimental PF through modulation of the TGF-β/Smad pathway. Interestingly, VPA treatment induced a higher expression of antifibrotic factors, such as Smad7. These results suggest that VPA may represent a potential strategy for treating long term PD complications.