Omer Celal Elcioglu

Lowering Uric Acid With Allopurinol Improves Insulin Resistance and Systemic Inflammation in Asymptomatic Hyperuricemia

Background Hyperuricemia is an independent predictor of impaired fasting glucose and type 2 diabetes, but whether it has a causal role in insulin resistance remains controversial. Here we tested the hypothesis that lowering uric acid in hyperuricemic nondiabetic subjects might improve insulin resistance. Methods Subjects with asymptomatic hyperuricemia (n = 73) were prospectively placed on allopurinol (n = 40) or control (n = 33) for 3 months. An additional control group consisted of 48 normouricemic subjects. Serum uric acid, fasting glucose, fasting insulin, HOMA-IR (homeostatic model assessment of insulin resistance), and high-sensitivity C-reactive protein were measured at baseline and at 3 months. Results Allopurinol-treated subjects showed a reduction in serum uric acid in association with improvement in fasting blood glucose, fasting insulin, and HOMA-IR index, as well as a reduction in serum high-sensitivity C-reactive protein. The number of subjects with impaired fasting glucose significantly decreased in the allopurinol group at 3 months compared with baseline (n = 8 [20%] vs n = 30 [75%], 3 months vs baseline, P < 0.001). In the hyperuricemic control group, only glucose decreased significantly and, in the normouricemic control, no end point changed. Conclusions Allopurinol lowers uric acid and improves insulin resistance and systemic inflammation in asymptomatic hyperuricemia. Larger clinical trials are recommended to determine if lowering uric acid can help prevent type 2 diabetes.

Effects of Allopurinol on Endothelial Dysfunction: A Meta-Analysis

Objective: Several studies have assessed the effect of allopurinol on endothelial function, but these studies were relatively small in size and used different methods of evaluating endothelial function. We conducted a meta-analysis to investigate the effect of allopurinol on both endothelial-dependent and -independent vasodilatation. Methods: Electronic databases, Medline, PubMed, EMBASE, SCOPUS, EBSCO and the Cochrane Library Central Register of Clinical Trials were searched from January 1985 to July 2013 on clinical trials (randomized and non-randomized) which assessed the effect of allopurinol on endothelial function. We conducted a sensitivity analysis to assess the contribution of each study to the pooled treatment effect by excluding each study one at a time and recalculating the pooled treatment effect for the remaining studies. Treatment effect was significant if p < 0.05. We assessed for heterogeneity in treatment estimates using the Cochran Q test and the χ2 statistic (with substantial heterogeneity defined as values >50%). Results: The final analysis consisted of 11 studies (2 observational and 9 randomized). For the endothelial-dependent vasodilatation there were 6 studies, including 257 patients, that evaluated flow-mediated dilatation and 5 studies with 87 patients that reported data on forearm blood flow response to acetylcholine or flow-dependent vasodilatation. Overall, there was a significant increase in the endothelium-dependent vasodilatation with allopurinol treatment (MD 2.69%, 95% CI 2.49, 2.89%, p < 0.001; heterogeneity χ2 = 319.1, I2 = 96%, p < 0.001). There was only 1 study (100 patients) assessing nitrate-mediated dilatation and 4 studies (73 patients) evaluating forearm blood flow response to sodium nitroprusside as measures of endothelial-independent vasodilatation. The overall analysis (MD -0.08, 95% CI -0.50, 0.34, p = 0.70; heterogeneity χ2 = 9.0, I2 = 44%, p = 0.11) showed no effect of allopurinol treatment on endothelium-independent vasodilatation. Conclusions: We found that treatment of hyperuricemia with allopurinol is associated with an improvement in the endothelial-dependent, but not with the endothelial-independent vasodilatation.

An unusual case of renal failure due to solitary plasmacytoma: parenchymal invasion of the kidney.

Abstract Solitary extramedullary plasmacytoma (EMP) is a rare plasma cell disorder mostly involving the upper airway; however, retroperitoneal infiltration is very rare. Kidney injury associated with EMP is exceptionally rare with only anecdotal reports. Herein we report a case of retroperitoneal EMP causing renal failure by the way of direct renal parenchymal infiltration. Renal parenchymal invasion should be considered in aggressive and refractory plasma cell dyscrasias with unexplained renal failure.

Reversible posterior leukoencephalopathy in the course of Goodpasture syndrome.

Abstract Reversible posterior leukoencephalopathy syndrome (RPLS) is characterized by headache, altered consciousness, seizures, and cortical blindness. The most frequent etiological factors are hypertension, kidney diseases, and immunosuppressive drugs such as steroids and cyclophosphamide. Herein we present a case of a 22-year-old female patient presented with alveolar hemorrhage and acute renal failure necessitating hemodialysis. In renal biopsy, necrotizing crescentic glomerulonephritis and immunofluorescence pattern compatible with Goodpasture syndrome were found. Anti-glomerular basement membrane antibody result was positive. At follow-up, respiratory failure ensued, steroid pulse treatment was started, and she was transferred to intensive care unit (ICU). In the ICU, she had visual disturbances and blindness together with seizures. Cranial magnetic resonance imaging (MRI) revealed irregular T2- and fluid-attenuated inversion recovery (FLAIR)-weighted lesions in bilateral occipital lobes. On clinical and radiological grounds, RPLS was diagnosed. With the supportive and anti-hypertensive treatment, RPLS was resolved without a sequela. Subsequent cranial MRI was totally normal. In the literature, RPLS associated with Goodpasture syndrome was reported only once. Hypertension and methylprednisolone might be the responsible etiologies in this case.

Chronic rhinosinusitis, endothelial dysfunction, and atherosclerosis.

Background Chronic inflammation is associated with accelerated atherosclerosis, endothelial dysfunction (ED), and cardiovascular diseases. Because chronic rhinosinusitis (CRS) is an inflammatory disease, it may be associated with the development of ED and accelerated atherosclerosis. Objective To investigate the relationship between CRS and carotid intima-media thickness (CIMT), flow-mediated dilation (FMD) of the brachial artery, and microalbuminuria. Materials and Methods This cross-sectional study included 38 patients with CRS and 29 healthy controls. In addition to measuring spot urine albumin-creatinine ratios, FMD of the brachial artery and CIMT were assessed noninvasively. Results Patients with CRS had lower FMD scores (p = 0.031), higher CIMT scores (p = 0.005), and a higher urinary albumin-creatinine ratio (p = 0.036) compared with healthy controls. In a multivariate analysis, CIMT and FMD were independently associated with the presence of CRS. However, the relationship between urinary albumin and creatinine, and the presence of CRS was no longer observed. Conclusions CRS is associated with ED and atherosclerosis, as indicated by decreased FMD and increased CIMT in patients with CRS. Further studies are necessary to identify the exact pathophysiologic mechanisms responsible for our findings.

Retrobulbar blood flow and carotid intima–media thickness alteration may relate to subclinic atherosclerosis in patients with chronic inflammatory diseases

Abstract Objective: AA amyloidosis occurs in the setting of longstanding inflammation. An increased incidence of coronary artery disease (CAD) was noted in patients with chronic inflammatory disease (CID). Retrobulbar blood flow predicts future macrovascular events including CAD. Increase in carotid artery intima–media thickness is regarded as a marker for early atherosclerosis. The relationship between chronic inflammation and atherosclerosis is well known; however, the connection between amyloidosis-advanced CIDs and retrobulbar microvascular function and carotid intima–media thickness (CIMT) is unidentified. We aimed to investigate whether retrobulbar microcirculation and CIMT were impaired or not in amyloidosis-advanced CID patients compared to normal subjects. Methods: Fourteen patients with renal AA amyloidosis and a group of healthy volunteers were included in the study. Measurement of CIMT and retrobulbar blood flow velocities was performed with ultrasound scanner and color Doppler ultrasonography. Results: The CIMT of patients with renal amyloidosis was significantly thicker than that of the normal population (p < 0.001). The resistivity index of the ophthalmic artery (OA) of patients with renal amyloidosis was significantly higher than the study group (p < 0.001). Conclusion: This study demonstrates that accelerated atherosclerosis which can be shown by increased OA resistivity index and CIMT are found in amyloidal-related CID patients.

Phenyramidol Induced Acute Tubular Necrosis

Phenyramidol is a moderately effective, non-narcotic analgesic and muscle relaxant. It acts by interneuronal block in the spinal cord and brain stem. The clearance of the drug becomes in the liver via glucuronidation. Conjugated form of the drug is excreted through the kidneys [1]. It is not available in the US or, with the exception of Turkey, in Europe. It is widely used for musculo-skeletal pain such as acute lumbago and chronic back pain in the Asia and Turkey, with or without NSAA°Ds. It rarely causes gastrointestinal discomfort and there are some reported cases of hepatotoxicity [2]. To the best of our knowledge, nephrotoxicity has not been reported yet. Herein, we reported a case of Acute Tubular Necrosis (ATN) possibly due to the use of phenyramidol for backache.

Crescentic glomerulonephritis due to IgA nephropathy or propylthiouracil-induced Mpo-Anca positive vasculitis?

A 48-year-old male patient with hyperthyroidism who had been treated with propylthiouracil (PTU) 400 mg/day presented with nausea and vomiting. Since serum creatinine was found 4.51 mg/dL and urinalysis revealed hematuria and 7.8 g/day proteinuria, renal biopsy was performed which showed IgA nephropathy and crescentic glomerulonephritis. Myeloperoxidase-antineutrophil cytoplasmic antibody (MPOANCA) was also found to be positive in high titers. PTU was withdrawn promptly and pulse methyl-prednisolone 1 g/day for 3 days and cyclophosphamide 600 mg was started intravenously. Afterwards oral maintenance treatment with methyl-prednisolone was administered in tapering doses. Currently the patient is followed in our Nephrology outpatient clinics with serum creatinine levels of 2 mg/dL without complaints. PTU, which is a common drug used for the treatment of hyperthyroidism, has several severe complications such as granulocytopenia, hepatitis and vasculitis. ANCA-positive crescentic glomerulonephritis due to PTU has also been well documented. 1,2 However IgA nephropathy together with PTU-induced ANCA-positive crescentic glomerulonephritis has been reported only once in the literature. 3 There are multiple possible explanations for the etiology of crescentic glomerulonephritis in our case; patient may have had previously subclinical IgA nephropathy unrelated to PTU use with the present clinical picture being an ANCA-positive glomerulonephritis secondary to PTU therapy or he may have had rapidly progressive IgA nephropathy only and PTU-induced ANCA positivity was only an incidental finding. Alternatively it may be hypothesized that these two cases represent a novel overlap syndrome of PTUinduced IgA nephropathy and ANCA-positive crescentic glomerulonephritis.

Cyclophosphamide induced early-onset interstitial lung disease

A 52-year-old woman was admitted to our hospital with persistent fatigue and pretibial edema. Serum creatinine was 2.7 mg/dL, and urine analysis revealed hematuria and pyuria. Proteinuria was 3 g/day. Tests for anti-neutrophil cytoplasmic antibody (ANCA) and anti-glomerular basement membrane antibody were negative. Based on renal biopsy, ANCA-negative pauci-immune crescentic glomerulonephritis was diagnosed. No abnormal findings were apparent on the baseline thorax computed tomography (CT) image (Fig. 1a). The patient was started on a pulse methylprednisolone regimen (1 g/day for 3 days) followed by 750 mg cyclophosphamide (CPA) per month. Following the pulse treatments, 1 mg/kg prednisolone was continued for an additional month, with tapering of the steriod dose by 4 mg/week. The maintenance dose of methyprednisolone was 4 mg/day. After the third dose of CPA, patient complained of exertional dyspnea and cough. The serum creatinine level and urinalysis results were normal. However, a second thorax CT showed the presence of a reticular interstitial infiltration with a honey-comb appearance (Fig. 1b). As the concomitant use of certain drugs is able to induce interstitial lung disease, we investigated this possibility but found no suspicious drug history. Infectious etiologies as possible causes of the clinical picture were also considered and subsequently excluded. The diagnosis of CPA-induced early-onset interstitial lung disease was established on clinical and radiological grounds. The CPA was withdrawn from the therapeutic regimen, and treatment with 1 mg/kg prednisolone was started. At follow-up, the dyspnea and cough had disappeared. Baseline and followup serum C-reactive protein levels after the treatment were 11.2 and 1.1 mg/dL, respectively. The presence of dyspnea and an interstitial pattern in a patient receiving CPA treatment suggests that a possible CPA-induced lung toxicity should be considered [1]. Prompt discontinuation of CPA and treatment with corticosteroids is usually followed by clinical recovery [2]. CPA-induced interstitial lung disease in patients with renal disease is a rare entity. Pulmonary toxicity of this drug is most commonly encountered in oncology patients. However, there have been several reports of an association between CPA treatment and various renal diseases, such as nephrotic syndrome and membranous glomerulonephritis [3, 4].