Relationship between prevalence and severity of restless legs syndrome and anemia in patients with systemic lupus erythematosus.

AIM: Our aim was to evaluate the relationship between the prevalence and severity of restless legs syndrome (RLS) and the anemia in patients with systemic lupus erythematosus (SLE). METHODS: This was a case-control study which was conducted at the rheumatology clinic of a university affiliated hospital, including 62 patients with SLE and 62 age- and sex-matched healthy controls. The patients were divided into two groups in terms of their hemoglobin levels. The criterion for anemia was hemoglobin level lower than 12 g/dL in females and 13 g/dL in males. RESULTS: Nineteen patients (30.6%) in the patient group were diagnosed with RLS, and International RLS Study Group Rating Scale (IRLSSG-RS) score was 10.7 ± 9.5 (median:10.0 [range:0.0-30.0]). Three subjects (4.8%) in the control group had RLS, and the IRLSSG-RS score was 0.7 ± 3.3 (median:0.0 [range:0.0-18.0]). The prevalence of RLS and the IRLSSG-RS score were higher in the patient group than those in the control group (P < 0.001). Ten SLE patients (50%) with anemia had RLS, and their IRLSSG-RS score was 14.5 ± 9.9 (median:21.0 [range:11.0-30.0]). Nine SLE patients (21.4%) without anemia had RLS and their IRLSSG-RS was 9.0 ± 8.9 (median:21.0 [range:11.0-24.0]). Significant differences were present in the prevalence of RLS and the IRLSSG-RS score between SLE patients with and without anemia (P = 0.024, P = 0.044, respectively). CONCLUSION: The present study demonstrated that the prevalence of RLS was higher in patients with SLE than that of the normal population. Results of this study also suggested that anemia was associated with higher frequency of and more severe RLS in patients with lupus.

Hypomagnesemia Among Outpatient Long-Term Proton Pump Inhibitor Users.

Proton pump inhibitors (PPIs) are extensively prescribed drugs usually used for a long period. Recent reports linked PPI use with development of hypomagnesemia. However, there is still uncertainty regarding risk of hypomagnesemia in outpatients who were on long-term PPI use. Thus, we aimed to evaluate frequency of hypomagnesemia among a well-defined outpatient patient cohort with no other possible risk factors affecting serum magnesium levels. This was a case-control study carried out at the outpatient gastroenterology clinic of a University hospital. Patients who were on PPI therapy for at least 6 months without diuretic use and chronic kidney disease were included. Patients who were subjected to the same inclusion and exclusion criteria and not using PPI were included as control subjects. One hundred fifty-four patients and 84 control subjects were included. The mean duration of PPI use was 27.5 ± 2.5 months. Mean serum magnesium levels of PPI users and nonusers were 2.17 ± 0.20 mg/dL and 2.19 ± 0.15 mg/dL, respectively. None of the patient had a serum magnesium level below laboratory lower range of 1.7 mg/dL. Our results showed that for typical gastroenterology outpatient clinic patients with no other risk factors affecting serum magnesium levels, long-term PPI use did not affect serum magnesium levels.

Isotretinoin use for acne vulgaris is associated with increased serum uric acid levels.

A few previous case reports related vitamin A and retinoid use with elevated serum uric acid (SUA) levels. Recently, a population based study showed an independent positive correlation of serum retinol with SUA levels. Despite increasing importance of SUA in a number of disease states, no study has examined the association between retinoids and SUA. We aimed to evaluate the effect of pharmacologic dose isotretinoin on SUA level. This was a cohort study in which 51 consecutive adult patients with severe acne vulgaris who were prescribed oral isotretinoin treatment (0.5 mg/kg) were included. Dermatologic examination was performed and SUA levels were measured at study inclusion for each participant, and then repeated at the first and second months of therapy. SUA levels at first month and second month were significantly higher than baseline SUA levels (p: 0.001, 0.007, respectively). SUA levels at second month were higher than SUA levels at first month, but the difference did not reach statistical significance. This study is the first to show that pharmacologic dose oral isotretinoin treatment significantly increased SUA levels. Since hyperuricemia is associated with renal disease, hypertension, atherosclerosis and metabolic syndrome as well as gout, it is important for the dermatologist to be aware of this potential adverse effect of isotretinoin particularly in vulnerable patients.

Colchicine in Renal Medicine: New Virtues of an Ancient Friend.

Colchicine is a plant-derived alkaloid that disrupts the cell microtubule system and accumulates in neutrophils, inhibiting neutrophil adhesion and recruitment. Colchicine has been used extensively in the prevention and treatment of gouty arthritis attacks, familial Mediterranean fever attacks and resultant AA amyloidosis, and recurrent pericarditis. Colchicine also disrupts the intracellular traffic of additional inflammatory and fibrosis mediators. Renal fibrosis is the final common pathway of chronic renal disease. Colchicine had anti-fibrotic effects in experimental diabetic nephropathy, renal mass reduction, and cyclosporine nephrotoxicity among others and is undergoing clinical trials for non-diabetic metabolic syndrome and diabetic nephropathy. In this review, we summarize the anti-inflammatory and anti-fibrotic properties of colchicine in experimental and clinical studies in renal diseases or other fibrotic disease processes with renal consequences. We also discuss the potential future uses of colchicine in renal medicine and challenges faced with its use in patients with impaired kidney function.

The Association of Vitamin D Status and Vitamin D Replacement Therapy with Glycemic Control, Serum Uric Acid Levels, and Microalbuminuria in Patients with Type 2 Diabetes and Chronic Kidney Disease.

OBJECTIVE: To evaluate the relationship of vitamin D status and vitamin D replacement therapy with glycemic control, serum uric acid (SUA) levels, and microalbuminuria (MAU) in patients with type 2 diabetes (T2DM) and chronic kidney disease (CKD). Subjectsand Methods: A total of 1,463 patients with T2DM and CKD (aged 14-88 years), 927 females and 536 males, were included in this study. The serum data of 25-hydroxyvitamin D, i.e., 25(OH)D, level, SUA, hemoglobin (Hb)A1c, creatinine, estimated glomerular filtration rate, and urine albumin-to-creatinine ratio (UACR) were obtained from the medical records. The Mann-Whitney U test, the χ2 test, the Mantel-Haenszel test, and linear regression models were used for data analysis. RESULTS: Vitamin D deficiency and insufficiency were evident in 770 (52.0%) and 357 (24.0%) patients, respectively. Median HbA1c levels (7.3 [IQR 3.9] vs. 6.5 [IQR 2.3]%; p < 0.01) were significantly higher in patients deficient in vitamin D than in those with a normal vitamin D status. A significantly low level of vitamin D was noted with a high UACR (ß -0.01; 95% CI -0.01 to -0.001; p = 0.017) and HbA1c (ß -1.1; 95% CI -1.6 to -0.6; p < 0.001), but with low levels of SUA (ß 1.3; 95% CI 0.5-2.2; p = 0.002). Vitamin D replacement was associated with a significantly low level of HbA1c (7.4 [2.7] vs. 6.7 [1.9]%; p < 0.001]. CONCLUSION: In this study, there was a high prevalence of hypovitaminosis D among T2DM patients with CKD, with a higher UACR, higher HbA1c, and lower SUA being noted as playing a role in predicting a decrease in vitamin D levels and potential benefits of vitamin D replacement therapy on glycemic control in T2DM management.

Serum Uric Acid and Risk for Acute Kidney Injury Following Contrast.

Contrast-induced acute kidney injury (CI-AKI) is a common cause of hospital-acquired acute kidney injury (AKI). We evaluated the evidence that uric acid (UA) plays a pathogenic role in CI-AKI. Ten studies were eligible for inclusion for meta-analysis. Hyperuricemia predicted risk for cases with AKI in prospective cohort studies. Higher levels of serum UA (SUA), as defined by the authors, were associated with a 2-fold increased risk to develop AKI (pooled odds ratio 2.03; 95% confidence interval [CI] 1.48-2.78). Significant heterogeneity was found in cohort studies ( P = .001, I2 = 85.7%). In 2 clinical trials, lowering of SUA with saline hydration was significantly associated with reduced risk for AKI compared with saline hydration alone or saline hydration with N-acetyl cysteine. An analysis of 2 randomized controlled trials found that allopurinol with saline hydration had a significant protective effect on renal function (assessed by serum creatinine values) compared with hydration alone (mean difference: -0.52 mg/dL; 95% CI: -0.81 to -0.22). Hyperuricemia independently predicts CI-AKI. Two clinical trials suggest lowering SUA may prevent CI-AKI. The mechanism by which UA induces CI-AKI is likely related to acute uricosuria.

Novel Faces of Fibroblast Growth Factor 23 (FGF23): Iron Deficiency, Inflammation, Insulin Resistance, Left Ventricular Hypertrophy, Proteinuria and Acute Kidney Injury.

FGF23 is a hormone that appears as the core regulator of phosphate metabolism. Great deal of data has accumulated to demonstrate increased FGF23 secretion from the bone to compensate for even subtle increases in serum phosphorus long before intact PTH. However, recent evidence points to the fact that actions and interactions of FGF23 are not limited solely to phosphate metabolism. FGF23 may be implicated in iron metabolism and erythropoiesis, inflammation, insulin resistance, proteinuria, acute kidney injury and left ventricular hypertrophy. In this review, we will summarize latest experimental and clinical data examining impact of FGF23 on aforementioned pathophysiologic pathways/disorders.

Sclerostin, cardiovascular disease and mortality: a systematic review and meta-analysis.

BACKGROUND AND AIM: Chronic kidney disease mineral and bone disorder (CKD-MBD) is associated with increased morbidity and mortality. Several cross-sectional studies investigated the association of serum sclerostin levels with mortality and vascular calcification. We aimed to investigate the effect of sclerostin on cardiovascular events (CVE), all-cause/cardiovascular mortality and vascular calcification in patients with CKD through systematic review and meta-analysis. The primary outcome was the association between sclerostin level and development of fatal and nonfatal CVE and all-cause mortality. MATERIALS AND METHODS: A literature search was performed using electronic databases Medline Ovid/Medline, PubMed/Medline, EMBASE and ISI Web of Science. Extracted hazard ratios from the included study protocols were pooled separately using the random-effects model (DerSimonian Laird). The equivalent z test was performed for each pooled HR, and if p < 0.05 it was considered statistically significant. RESULTS: In our final analysis, we included nine observational prospective studies involving 1788 patients (minimum 91 and maximum 673 patients). For the all-cause mortality, three studies with 503 patients showed that sclerostin levels were not significantly associated with all-cause mortality risk (HR = 1.01, 95 % CI 0.99-1.03, p = 0.16; heterogeneity χ 2 = 12.24, I 2 = 84 %, p = 0.002). For cardiovascular mortality, two studies with 412 patients showed that sclerostin levels were not significantly associated with cardiovascular mortality risk (HR = 1.03, 95 % CI 0.99-1.07, p = 0.17; heterogeneity χ 2 = 10.74, I 2 = 91 %, p = 0.001). CONCLUSION: Although the studies are mostly small in size, heterogeneous and have conflicting results, we have demonstrated that serum sclerostin levels were not associated with all-cause and cardiovascular mortality.

The role of sodium intake in nephrolithiasis: epidemiology, pathogenesis, and future directions.

The prevalence of nephrolithiasis has doubled over the last decade and the incidence in females now approaches that of males. Since dietary salt is lithogenic, a purported mechanism common to both genders is excess dietary sodium intake vis-a-vis processed and fast foods. Nephrolithiasis has far-reaching societal implications such as impact on gross domestic product due to days lost from work (stone disease commonly affects working adults), population-wide carcinogenic diagnostic and interventional radiation exposure (kidney stone disease is typically imaged with computed tomographic imaging and treated under imaging guidance and follow-up), and rising healthcare costs (surgical treatment will be indicated for a number of these patients). Therefore, primary prevention of kidney stone disease via dietary intervention is a low-cost public health initiative with massive societal implications. This primer aims to establish baseline epidemiologic and pathophysiologic principles to guide clinicians in sodium-directed primary prevention of kidney stone disease.

Renal functional reserve and renal hemodynamics in hypertensive patients.

The renal functional reserve (RFR) is the ability of the kidneys to increase renal plasma flow and glomerular filtration rate (GFR) in response to protein intake. It is a measure of functional and anatomic integrity of nephrons. It is not known what relation between RFR and kidney Doppler parameters. We aimed to study the relation between the RFR and renal hemodynamic parameters in hypertensive patients with and without nephropathy who had normal kidney function. Twenty-four hypertensive subjects with nephropathy (HTN-n, n = 10) and hypertension without nephropathy (HTN, n = 14) were included in the study. Control group included 11 healthy subjects. Baseline GFR (GFR1) and GFR after intake of egg protein 1 mg/kg of body weight were determined (GFR2). RFR was calculated by the following formula: (GFR2-GFR1)/GFR1 × 100%. Doppler ultrasonography was performed. Arterial blood pressure (BP), body mass index (BMI), and estimated GFR were also recorded. HTN and HTN-n groups had impaired levels of RFR compared with controls (p < 0.05), significantly decreased value of flow velocity parameters (Vmax, Vmin), and increased RRI compared with controls. There was significant negative correlation of RFR with blood pressure levels (sBP, r = -0.435, p = 0.009; dBP, r = -0.504, p = 0.002), RRI (r = -0.456, p = 0.008), micro albuminuria (MAU, r = -0.366, p = 0.031) and positive correlation with Vmax and Vmin (r = 0.556, p = 0.001 and r = 0.643, respectively, p < 0.001). Linear regression showed that RRI and MAU were independent predictors of decreased RFR. RFR is lower in hypertensive patients despite near-normal level of kidney function and is related to particular level of BP. RRI and MAU were independent predictors of decreased RFR.

Splenic artery embolization with Ankaferd blood stopper in a sheep model.

PURPOSE: Splenic artery embolization is a minimally invasive therapeutic procedure utilized in a number of disorders. Ankaferd blood stopper (ABS) is a novel hemostatic agent with a new mechanism of action independent of clotting factors. We aimed to investigate the safety and efficiency of ABS for splenic artery embolization in a sheep model. METHODS: Seven adult female sheep were included in the study. Selective celiac angiography was performed using a 5F diagnostic catheter and then a 2.7F hydrophilic coating microcatheter was advanced coaxially to the distal part of the main splenic artery. Under fluoroscopic guidance, 6 mL mixture composed of half-and-half ABS and contrast agent was slowly injected. Fluoroscopy was used to observe the deceleration and stagnation of the flow. Control celiac angiograms were obtained immediately after the embolization. After the procedure, the animals were observed for one day and then sacrificed with intravenous sodium thiopental. RESULTS: Technical success rate was 100%. None of the animals died or experienced a major systemic adverse event during the procedure. All of the spleens appeared dark on macroscopic examination due to excessive thrombosis. Microscopically, the majority of the splenic sinusoids (90%-95%) were necrotic. CONCLUSION: In our study, splenic artery embolization by ABS was found to be safe and effective in the short-term. Further studies are needed to better understand the embolizing potential of this novel hemostatic agent.

Novel Masters of Erythropoiesis: Hypoxia Inducible Factors and Recent Advances in Anemia of Renal Disease.

Anemia seen in patients with chronic kidney disease is a particular form of 'anemia of chronic disease'. Although multifactorial in origin, erythropoiesis-stimulating agents (ESAs) and adjuvant iron therapy represent the primary treatment for anemia in chronic kidney disease. Subsequent clinical observations revealed that these ESA hyporesponsive patients often had increased systemic inflammation as a consequence of their comorbidities. Use of high ESA doses to overcome this ESA hyporesponsiveness posed some concerns regarding associated adverse events of therapy and increased mortality in this special patient population. Recognizing the pivotal roles of hypoxia inducible factors (HIFs) in orchestrating elements of erythropoiesis opened new avenues in the management of renal anemia. Several phase 1 and 2 studies confirmed the results of early experimental studies supporting the beneficial role of augmenting HIFs for erythropoiesis. In this review, we describe the physiologic functions of HIF in erythropoiesis with special emphasis on interactions with iron and hepcidin metabolism and inflammation.

Is there any potential or additive effect of anemia on hepatorenal syndrome?

BACKGROUND/AIMS: Hepatorenal syndrome (HRS) is a severe complication of advanced cirrhosis and is characterized by renal dysfunction and poor survival rates. Although anemia is a non-rare condition in advanced liver cirrhosis, there is no publication regarding the potential or additive effects of anemia on HRS and renal dysfunction in patients with cirrhosis. We investigated whether severe anemia is a precipitant factor for HRS. MATERIALS AND METHODS: In this prospective study, consecutive patients with cirrhosis with and without renal dysfunction were enrolled. A total of 29 patients with cirrhosis with HRS meeting the HRS diagnostic criteria (9 patients with type 1 HRS and 20 with type 2 HRS) and 37 patients with cirrhosis without HRS were included. The demographic features, laboratory data (particularly anemic parameters), and clinical scores of patients with and without HRS were evaluated. RESULTS: Grades of ascites, Child-Turcotte-Pugh (CTP) scores, and Model of End Stage Liver Disease (MELD) scores were significantly higher in contrast to hemoglobin levels; hematocrit concentrations were significantly lower in patients with type 1 and 2 HRS than in those with non-HRS stable cirrhosis. There was a negative correlation between the hemoglobin-hematocrit and serum creatinine levels. In the logistic regression analysis, the hemoglobin levels and CTP and MELD scores were statistically significant for an onset of HRS. CONCLUSION: Anemia may contribute to HRS and deteriorated renal function in patients with HRS because anemic hypoxia can lead to microcirculatory renal ischemia in the kidneys and anemia can also activate sympathetic activity and hyperdynamic circulation in the pathogenesis of HRS.

Comparison of serum sodium levels measured by blood gas analyzer and biochemistry autoanalyzer in patients with hyponatremia, eunatremia, and hypernatremia.

BACKGROUND: Blood gas analyzer (BGA) electrolyte measurements are frequently used in emergency departments (EDs) pending biochemistry laboratory autoanalyzer (BLA) results. There is lack of data in the literature in terms of agreement of these 2 measurement methods of sodium. We aimed to comprehensively evaluate the agreement in hyponatremia, eunatremia, and hypernatremia groups. METHODS: Retrospectively, adult subjects who presented to ED of a tertiary care teaching hospital and had simultaneous BGA and BLA results were included in the study. Blood pairs were grouped into hyponatremia, eunatremia, and hypernatremia according to BLA results. Agreement of sodium measurements between the methods were evaluated by Bland-Altman plots and Passing and Bablok regression analysis. RESULTS: A total of 2557 blood pairs (1326 males [51.8%]) were included. Median age of the patients was 66 years (18-103). The numbers of patients with hyponatremia, eunatremia, and hypernatremia were 487 (19%), 1943 (76%), and 127 (5%), respectively. The minimum and maximum serum sodium levels measured by biochemistry analyzer were 106 and 171 mmol/L, respectively. The Pearson linear correlation coefficient between BGA and BLA for sodium measurements were 0.574, 0.358, and 0.562 in hyponatremia, eunatremia, and hypernatremia groups, respectively. The absolute mean difference for the 3 groups was greater than 4 mmol/L. Biochemistry laboratory autoanalyzer tended to measure serum sodium higher than BGA in all sodium groups. Passing and Bablok regression analysis showed significant differences between the 2 methods in all sodium groups. CONCLUSION: This is the first comprehensive evaluation of agreement between BGA and BLA in distinct sodium groups. Significant differences should be taken into account when these patients are managed in the ED.

Retrospective analysis of lactic acidosis-related parameters upon and after metformin discontinuation in patients with diabetes and chronic kidney disease.

PURPOSE: To investigate association between renal functions, lactic acid levels and acid-base balance in type 2 diabetes patients with chronic kidney disease under metformin treatment and after metformin discontinuation in a real-life setting. METHODS: A total of 65 patients with diabetes (mean age 68.5 ± 8.9 years, 56.9 % females) in whom metformin treatment was discontinued due to reduced glomerular filtration rate (GFR) were included in this retrospective study. Data on patient demographics, metformin treatment and laboratory findings on the last day of metformin treatment and 2-3 weeks after metformin discontinuation including blood lactate and creatinine, estimated glomerular filtration rate (eGFR) and acid-base balance measurements in blood [pH, bicarbonate, base excess] were collected from medical records. The correlation of lactate levels with eGFR, blood pH and creatinine levels and changes in laboratory findings after metformin discontinuation were evaluated. RESULTS: Before metformin discontinuation, hyperlactatemia was observed in 78.5 % of patients and metabolic acidosis in 36.9 % of patients, but none had lactic acidosis. Patients with normolactatemia and hyperlactatemia were similar in terms of metformin dosage and laboratory parameters. Lactate levels were not significantly correlated with serum creatinine (r = -0.14; p = 0.263) and eGFR (r = 0.11, p = 0.374). After metformin discontinuation, a significant decrease was observed in median lactate levels (from 2.20 to 1.85 mmol/L; p = 0.002). CONCLUSION: In conclusion, our findings support the low risk of MALA among patients with mild-to-moderate renal impairment and the likelihood of metformin to be an innocent bystander without a pathogenic role in the lactic acidosis in most cases.

Hypertension as an autoimmune and inflammatory disease.

Hypertension that is considered idiopathic is called essential hypertension and accordingly has no clear culprit for its cause. However, basic research and clinical studies in recent years have expanded our understanding of the mechanisms underlying the development of essential hypertension. Of these, increased oxidative stress, both in the kidney and arterial wall, closely coupled with inflammatory infiltration now appear to have a prominent role. Discovery of regulatory and interleukin-17-producing T cells has enabled us to better understand the mechanism by which inflammation and autoimmunity, or autoinflammation, lead to the development of hypertension. Despite achieving considerable progress, the intricate interactions between oxidative stress, the immune system and the development of hypertension remain to be fully elucidated. In this review, we summarize recent developments in the pathophysiology of hypertension with a focus on the oxidant stress-autoimmunity-inflammation interaction.

Atherosclerotic renal artery stenosis in the post-CORAL era part 2: new directions in Transcatheter Nephron Salvage following flawed revascularization trials.

Unlike endovascular therapeutic studies for atherosclerosis in many other vascular beds, major trials regarding endovascular renovascular revascularization have resulted in a stagnating equipoise. However, every major trial completed for this topic thus far has suffered from major methodological flaws that limit the validity and external generalizability of their results. Furthermore, certain patient populations who are known to benefit from renovascular revascularization may never be studied because they cannot be ethically withheld from life-saving treatment. Forthcoming percutaneous techniques may one day complement angioplasty and stenting in a burgeoning era of cellular modulation and endovascular-directed renal regeneration.

The role of neutrophil lymphocyte ratio to leverage the differential diagnosis of familial Mediterranean fever attack and acute appendicitis.

BACKGROUND/AIMS: Familial Mediterranean fever (FMF) is an autosomal recessive disorder characterized by attacks of fever and diffuse abdominal pain. The primary concern with this presentation is to distinguish it from acute appendicitis promptly. Thus, we aimed to evaluate the role of neutrophil lymphocyte ratio (NLR) to leverage the differential diagnosis of acute FMF attack with histologically proven appendicitis. METHODS: Twenty-three patients with histologically confirmed acute appendicitis and 88 patients with acute attack of FMF were included in the study. NLR, C-reactive protein and other hematologic parameters were compared between the groups. RESULTS: Neutrophil to lymphocyte ratio was significantly higher in patients with acute appendicitis compared to the FMF attack group (8.24 ± 6.31 vs. 4.16 ± 2.44, p = 0.007). The performance of NLR in diagnosing acute appendicitis with receiver operating characteristic analysis with a cut-off value of 4.03 were; 78% sensitivity, 62% specificity, and area under the curve 0.760 (95% confidence interval, 0.655 to 0.8655; p < 0.001). CONCLUSIONS: This study showed that NLR, the simple and readily available inflammatory marker may have a useful role in distinguishing acute FMF attack from acute appendicitis.