Sarah Chung

Pretreatment of sildenafil attenuates ischemia-reperfusion renal injury in rats

Sildenafil was the first selective inhibitor of phosphodiesterase-5 (PDE5) to be widely used for treating erectile dysfunction. Many recent studies have investigated the cardioprotective role of sildenafil in animal models. We evaluated the protective effects of sildenafil in experimental renal ischemia-reperfusion (IR) injury in two studies. In study 1, male Sprague-Dawley rats were divided into four groups: sham, sildenafil-treated sham, vehicle-treated IR, and sildenafil-treated IR groups. In study 2, we divided the rats into two groups: sildenafil-treated IR rats and PD98059 (ERK inhibitor)+sildenafil-treated IR rats. Functional parameters of the kidney were evaluated at the molecular and structural levels. Blood urea nitrogen (BUN) and serum creatinine levels were lower in sildenafil-treated IR rats than in vehicle-treated IR rats. The expression of inducible (iNOS) and endothelial nitric oxide synthase (eNOS) proteins in sildenafil-treated IR rats was significantly higher than in vehicle-treated IR rats. Pretreatment with sildenafil in IR rats increased ERK phosphorylation and reduced the renal Bax/Bcl-2 ratio, renal caspase-3 activity, and terminal dUTP nick end-labeling-positive apoptotic cells. In contrast, PD98059 treatment increased BUN and serum creatinine levels and attenuated the sildenafil-induced expression of pERK, iNOS, eNOS, and Bcl-2. PD98059 also increased caspase-3 activity but did not decrease the sildenafil-induced accumulation of cGMP. In conclusion, this study suggests that sildenafil has antiapoptotic effects in experimental IR renal injury via ERK phosphorylation, induction of iNOS and eNOS production, and a decrease in the Bax/Bcl-2 ratio.

Overhydration measured by bioimpedance analysis and the survival of patients on maintenance hemodialysis: a single-center study

Background Bioimpedance analysis (BIA) helps measuring the constituents of the body noninvasively. Prior studies suggest that BIA-guided fluid assessment helps to predict survival in dialysis patients. We aimed to evaluate the clinical usefulness of BIA for predicting the survival rate of hemodialysis patients in Korea. Methods We conducted a single-center retrospective study. All patients were diagnosed with end-stage renal disorder and started maintenance hemodialysis between June 2009 and April 2014. BIA was performed within the 1st week from the start of hemodialysis. The patients were classified into 2 groups based on volume status measured by the body composition monitor (BCM; Fresenius): an overhydrated group [OG; overhydration/extracellular water (OH/ECW) >15%] and a nonoverhydrated group (NOG; OH/ECW ≤15%). Results A total of 344 patients met the inclusion criteria. Of these, 252 patients (73.3%) were categorized into the OG and 92 patients (26.7%) into the NOG. Age- and sex-matching patients were selected with a rate of 2:1. Finally, 160 overhydrated patients and 80 nonoverhydrated patients were analyzed. Initial levels of hemoglobin and serum albumin were significantly lower in the OG. During follow-up, 43 patients from the OG and 7 patients from the NOG died (median follow-up duration, 24.0 months). The multivariate-adjusted all-cause mortality was significantly increased in the OG (odds ratio, 2.569; P = 0.033) and older patients (odds ratio, 1.072/y; P < 0.001). No significant difference of all-cause or disease-specific admission rate was observed between the 2 groups. Conclusion The ratio of OH/ECW volume measured with body composition monitor is related to the overall survival of end-stage renal disorder patients who started maintenance hemodialysis.

Renal actinomycosis with concomitant renal vein thrombosis.

Renal actinomycosis is a rare infection caused by fungi of the genus Actinomyces. A 74-year-old male was admitted to our hospital because of gross hematuria with urinary symptoms and intermittent chills. Computed tomography of the abdomen showed thrombosis in the left renal vein and diffuse, heterogeneous enlargement of the left kidney. After nephrectomy, sulfur granules with chronic suppurative inflammation were seen microscopically, and the histopathological diagnosis was renal actinomycosis. Our case is the first report of renal actinomycosis with renal vein thrombosis.

Spontaneous bladder rupture in a chronic hemodialysis patient.

Spontaneous bladder rupture is very rare. A 67-year-old woman who was nearly anuric and had been on chronic hemodialysis therapy for diabetic end-stage renal disease for 6 years complained of severe low abdominal pain and fever for 2 days. Abdominal computerized tomography and retrograde cystography revealed the extraperitoneal leakage of contrast medium, confirming bladder perforation. Partial cystectomy around the perforation site and repair of the bladder rupture were performed. Microscopic examination of the excised bladder tissue revealed that the bladder mucosa was ulcerated. Severe suppurative inflammation was observed throughout the bladder wall. Antibiotic treatment was continued for 3 weeks postoperatively, and repeated retrograde cystography showed no evidence of contrast extravasation. She was discharged, with no other complications.

Concomitant inhibition of renin angiotensin system and Toll-like receptor 2 attenuates renal injury in unilateral ureteral obstructed mice.

Background/Aims: There has been controversy about the role of Toll-like receptor 2 (TLR2) in renal injury following ureteric obstruction. Although inhibition of the renin angiotensin system (RAS) reduces TLR2 expression in mice, the exact relationship between TLR2 and RAS is not known. The aim of this study was to determine whether the RAS modulates TLR2. Methods: We used 8-week-old male wild type (WT) and TLR2-knockout (KO) mice on a C57Bl/6 background. Unilateral ureteral obstruction (UUO) was induced by complete ligation of the left ureter. Angiotensin (Ang) II (1,000 ng/kg/min) and the direct renin inhibitor aliskiren (25 mg/kg/day) were administrated to mice using an osmotic minipump. Molecular and histologic evaluations were performed. Results: Ang II infusion increased mRNA expression of TLR2 in WT mouse kidneys (p < 0.05). The expression of renin mRNA in TLR2-KO UUO kidneys was significantly higher than that in WT UUO kidneys (p < 0.05). There were no differences in tissue injury score or mRNA expression of monocyte chemotactic protein 1 (MCP-1), osteopontin (OPN), or transforming growth factor β (TGF-β) between TLR2-KO UUO and WT UUO kidneys. However, aliskiren decreased the tissue injury score and mRNA expression of TLR2, MCP-1, OPN, and TGF-β in WT UUO kidneys (p < 0.05). Aliskiren-treated TLR2-KO UUO kidneys showed less kidney injury than aliskiren-treated WT UUO kidneys. Conclusions: TLR2 deletion induced activation of the RAS in UUO kidneys. Moreover, inhibition of both RAS and TLR2 had an additive ameliorative effect on UUO injury of the kidney.

Clinical Characteristics of Overhydration in Patients with Idiopathic Edema.

Background: Idiopathic edema (IE) is a common clinical syndrome. Designing treatment plans for IE is problematic because of the difficulty in assessing volume status. We aimed to evaluate volume status, measured by bioimpedance spectroscopy (BIS), and investigated clinical parameters associated with volume overload (VO) in patients with IE. Methods: Patients with IE were defined as those with symptomatic edema and without abnormal renal function or any other apparent cause of edema. A total of 124 patients were included. Overhydration (OH) and extracellular water (ECW) were calculated using BIS. Relative hydration status (ΔHS) was defined as OH/ECW. Patients were classified into 2 groups: overhydrated group (OG; ΔHS ≥7%) and non-OG (NOG; ΔHS <7). Simple and multiple logistic regression analyses were used to assess the influence of several variables on the incidence of VO. Results: Of 124 patients, 37 (29.8%) were in the OG. The proportion of men in the OG was higher than that in the NOG (p = 0.020). Patients in the OG showed more frequent pretibial pitting edema (PTPE, p < 0.001) and had lower hemoglobin (p = 0.008) and serum albumin levels (p < 0.001). The multivariate analysis showed that the presence of PTPE (OR 10.62, 95% CI 1.98-57.1), low serum albumin level (OR 0.01, 95% CI 0.00-0.25) and lower fat tissue index (OR 0.78, 95% CI 0.63-0.97) were independent risk factors for the presence of VO. Conclusions: BIS helps to identify volume status and body composition in patients with IE.

Rhabdomyolysis in a patient taking nebivolol.

β Blockers such as propranolol and labetalol are known to induce toxic myopathy because of their partial β2 adrenoceptor agonistic effect. Nebivolol has the highest β1 receptor affinity among β blockers, and it has never been reported to induce rhabdomyolysis until now. We report a patient who developed rhabdomyolysis after changing medication to nebivolol. A 75-year-old woman was admitted to our hospital because of generalized weakness originating 2 weeks before visiting. Approximately 1 month before her admission, her medication was changed from carvedilol 12.5 mg to nebivolol 5 mg. Over this time span, she had no other lifestyle changes causing rhabdomyolysis. Her blood chemistry and whole body bone scan indicated rhabdomyolysis. We considered newly prescribed nebivolol as a causal agent. She was prescribed carvedilol 12.5 mg, which she was previously taking, instead of nebivolol. She was treated by hydration and urine alkalization. She had fully recovered and was discharged.

The Impact of Hemodialysis and Arteriovenous Access Flow on Extracranial Hemodynamic Changes in End-Stage Renal Disease Patients

In this study, we characterized cerebral blood flow changes by assessment of blood flow parameters in neck arteries using carotid duplex ultrasonography and predictive factors for these hemodynamic changes. Hemodynamic variables were measured before and during hemodialysis in 81 patients with an arteriovenous access in their arm. Hemodialysis produced significant lowering in peak systolic velocity and flow volume of neck arteries and calculated total cerebral blood flow (1,221.9 ± 344.9 [before hemodialysis] vs. 1,085.8 ± 319.2 [during hemodialysis], P < 0.001). Effects were greater in vessels on the same side as the arteriovenous access and these changes were influenced by arteriovenous access flow during hemodialysis, both in the CCA (r = -0.277, P = 0.015) and the VA (r = -0.239, P = 0.034). The change of total cerebral blood flow during hemodialysis was independently related with age, presence of diabetes, and systemic blood pressure.

Rupture of an infectious pseudoaneurysm of the aortic arch in an end-stage renal failure patient with chronic hemodialysis.

In hemodialysis patients, vascular access infection remains a significant cause of morbidity and mortality. It has various complications, including bacterial endocarditis, spinal epidural abscess, osteomyelitis, septic arthritis, and septic pulmonary emboli. However, aortitis with infected pseudoaneurysm formation is very rare. Here, we report a case of necrotizing aortitis in a hemodialysis patient with an arteriovenous graft infection.

A Case of Membranous Glomerulonephritis with Superimposed Anti-Neutrophil Cytoplasmic Antibody-Associated Rapidly Progressive Crescentic Glomerulonephritis.

Idiopathic membranous glomerulonephritis (IMGN) is commonly diagnosed in adults with proteinuria. Rapid deterioration of renal function is a rare complication of IMGN, except when accompanied by renal vein thrombosis, malignant hypertension, or other underlying disease, including lupus nephritis. Here, we present a case of rapid deterioration of renal function in a patient with MGN superimposed with anti-neutrophil cytoplasmic antibody (ANCA)-associated rapidly progressive crescentic glomerulonephritis (RPGN). Overall, about 20 cases of MGN with ANCA-associated RPGN have been reported. This case of biopsy-proven MGN with ANCA-associated RPGN is the first to be reported in Korea.