TASL Practice Guidance on the Clinical Assessment and Management of Patients with Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is a multisystem disease and is significantly associated with obesity, insulin resistance, type 2 diabetes mellitus, metabolic syndrome, and cardiovascular disease. NAFLD has become the most prevalent chronic liver disease in Western countries, and the proportion of NAFLD-related cirrhosis among patients on liver transplantation waiting lists has increased. In light of the accumulated data about NAFLD, and to provide a common approach with multi-disciplines dealing with the subject, it has become necessary to create new guidance for diagnosing and treating NAFLD. This guidance was prepared following an interdisciplinary study under the leadership of the Turkish Association for the Study of the Liver (TASL), Fatty Liver Special Interest Group. This new TASL Guidance is a practical application guide on NAFLD and was prepared to standardize the clinical approach to diagnosing and treating NAFLD patients. This guidance reflects many advances in the field of NAFLD. The proposals in this guidance are meant to aid decision-making in clinical practice. The guidance is primarily intended for gastroenterology, endocrinology, metabolism diseases, cardiology, internal medicine, pediatric specialists, and family medicine specialists.

Membranous Nephropathy with Lambda Light Chain Restriction: A Rare Form with Serum Negative and Tissue Positive PLA2R Ab.

Membranous nephropathy (MN) is the most common cause of nephrotic syndrome in adults. Subepithelial polyclonal immunoglobulin deposits and >70% M-type phospholipase A2 receptor antibody positivity are typical findings in idiopathic MN. A 58-year-old female patient was admitted with clinical presentation of nephrotic syndrome. Autoimmune diseases, infections, and malignancies were ruled out after clinical and laboratory evaluations. Diagnostic work-up revealed serum PLA2R antibody negativity and diffuse thickening of glomerular capillary wall on biopsy, while glomerular capillary wall IgG, C3, and Lambda monotypic light chain deposition and PLA2R1 positivity were detected by immunofluorescence and immunohistochemical examination, respectively. Following prednisolone treatment, creatinine and proteinuria were markedly regressed. The MN cases with a light chain deposits are rare and experience regarding their treatment are insufficient.

A multicenter study of the clinical, laboratory characteristics, and potential prognostic factors in patients with amyloid A amyloidosis on hemodialysis.

INTRODUCTION: While light chain (AL) amyloidosis is more common in western countries, the most common type of amyloidosis is amyloid A (AA) amyloidosis in Eastern Mediterranean Region, including Turkey. Although worse prognosis has been attributed to the AL amyloidosis, AA amyloidosis can be related to higher mortality under renal replacement therapies. However, there are no sufficient data regarding etiology, clinical presentation, and prognostic factors of AA amyloidosis. The objective of our study is to evaluate the clinical, laboratory characteristics, and possible predictive factors related to mortality in patients with AA amyloidosis undergoing hemodialysis (HD). METHODS: This multicenter, cross-sectional study was a retrospective analysis of 2100 patients on HD. It was carried out in 14 selected HD centers throughout Turkey. Thirty-two patients with biopsy-proven AA amyloidosis and thirty-two control patients without AA amyloidosis undergoing HD were included between October 2018 and October 2019. There was no significant difference between the groups in terms of age and dialysis vintage. Causes of AA amyloidosis, treatment (colchicine and/or anti-interleukin 1 [IL] treatment), and the number of familial Mediterranean fever (FMF) attacks in the last year in case of FMF, systolic and diastolic blood pressures, biochemical values such as mean CRP, hemoglobin, serum albumin, phosphorus, calcium, PTH, ferritin, transferrin saturation, total cholesterol levels, EPO dose, erythropoietin-stimulating agents resistance index, interdialytic fluid intake, body mass indexes, heparin dosage, UF volume, and Kt/V data in the last year were collected by retrospective review of medical records. FINDINGS: Prevalence of AA amyloidosis was found to be 1.87% in HD centers. In amyloidosis and control groups, 56% and 53% were male, mean age was 54 ± 11 and 53 ± 11 years, and mean dialysis vintage was 104 ± 94 and 107 ± 95 months, respectively. FMF was the most common cause of AA amyloidosis (59.5%). All FMF patients received colchicine and the mean colchicine dose was 0.70 ± 0.30 mg/day. 26.3% of FMF patients were unresponsive to colchicine and anti-IL-1 treatment was used in these patients. In AA amyloid and control groups, erythropoietin-stimulating agents resistance index were 7.88 ± 3.78 and 5.41 ± 3.06 IU/kg/week/g/dl, respectively (p = 0.008). Additionally, higher CRP values (18.78 ± 18.74 and 10.61 ± 10.47 mg/L, p = 0.037), lower phosphorus (4.68 ± 0.73 vs. 5.25 ± 1.04 mg/dl, p = 0.014), total cholesterol (135 ± 42 vs. 174 ± 39 mg/dl, p < 0.01), and serum albumin (3.67 ± 0.49 mg/dl, 4.03 ± 0.22, p < 0.01) were observed in patients with AA amyloidosis compared to the control group. DISCUSSION: In this study, we found that long-term prognostic factors including higher inflammation, malnutritional parameters, and higher erythropoietin-stimulating agents resistance index were more frequent in AA amyloidosis patients under HD treatment.

Warfarin is associated with the risk of vascular calcification in abdominal aorta in hemodialysis patients: a multicenter case-control study.

BACKGROUND: Vascular calcifications (VCs), recognized risk factor for increased mortality, are highly prevalent in hemodialysis (HD) patients. We aimed to investigate the relation between VC and warfarin use with plain radiography. METHODS: VCs were assessed using Adragao (radial and digital) and Kauppila (aortic) scores in 76 HD patients from six centers. Out of a total 711 HD patients, there were 32 (4.5%) who had been treated with warfarin for at least 1 year, and we included 44 control patients. RESULTS: Of the patients, 47% were females, the mean age was 66 ± 9 years, 23% were diabetics, the mean dialysis vintage was 68 ± 38 months. In warfarin group, median Kauppila score was higher than in control group [11 vs 6.5, (25%-75% percentile, 5 vs. 15), p = 0.032] and the percentage of the patients with a Kauppila score of >6 was higher, as well (76.6% vs. 50%; p = 0.029). Median Adragao score was not significantly different between the two groups [7 vs. 6, (%25,%75 percentile 6 vs. 8), p = 0.17]. Logistic regression analysis revealed that warfarin treatment was independently associated with Kauppila scores of >6 (OR 3.60, 95% CI 1.18-10.9, p = 0.024). DISCUSSION: In this study, we found that warfarin is associated to vascular calcifications, especially in aorta of HD patients.

Does maternal hydronephrosis have an impact on urinary neutrophil gelatinase-associated lipocalin (uNGAL) levels?

OBJECTIVE: To determine urinary neutrophil gelatinase-associated lipocalin (uNGAL) levels and creatinine clearance values in women with different degrees of asymptomatic hydronephrosis during pregnancy. METHODS: A total of 44 pregnant women with different degrees of hydronephrosis and 46 without hydronephrosis were consecutively enrolled in this prospective study. Basic serum and urine parameters, uNGAL levels, and creatinine clearance values were evaluated. All results were compared between the two groups. Regression analysis was used to determine independent predictors, which were mostly related to hydronephrosis. RESULTS: Demographic data, basal laboratory parameters, and creatinine clearance values were similar, whereas significantly higher uNGAL levels were detected in women with hydronephrosis compared to those without hydronephrosis (45.3 versus 33.2 ng/mL, respectively) (p = 0.004). An increasing trend in uNGAL levels was detected with increasing degrees of hydronephrosis; as it was not statistically significant (p = 0.163). Linear regression analysis revealed that the parameter of "pelvic diameter" was found as a significant independent factor influencing uNGAL concentrations (ß = 0.289; 95% CI: 0.522-3.061; p = 0.006). Other independent variables were not found to influence uNGAL concentrations (p > 0.05). CONCLUSION: The results obtained from this study indicate a significant increase of urinary concentration of NGAL in the presence of asymptomatic maternal hydronephrosis. This impact is likely to be more profound in those with severe hydronephrosis although this has not been specifically investigated. This theory needs to be validated in larger populations.

Behçet's: A Disease or a Syndrome? Answer from an Expression Profiling Study.

Behçet's disease (BD) is a chronic, relapsing, multisystemic inflammatory disorder with unanswered questions regarding its etiology/pathogenesis and classification. Distinct manifestation based subsets, pronounced geographical variations in expression, and discrepant immunological abnormalities raised the question whether Behçet's is "a disease or a syndrome". To answer the preceding question we aimed to display and compare the molecular mechanisms underlying distinct subsets of BD. For this purpose, the expression data of the gene expression profiling and association study on BD by Xavier et al (2013) was retrieved from GEO database and reanalysed by gene expression data analysis/visualization and bioinformatics enrichment tools. There were 15 BD patients (B) and 14 controls (C). Three subsets of BD patients were generated: MB (isolated mucocutaneous manifestations, n = 7), OB (ocular involvement, n = 4), and VB (large vein thrombosis, n = 4). Class comparison analyses yielded the following numbers of differentially expressed genes (DEGs); B vs C: 4, MB vs C: 5, OB vs C: 151, VB vs C: 274, MB vs OB: 215, MB vs VB: 760, OB vs VB: 984. Venn diagram analysis showed that there were no common DEGs in the intersection "MB vs C" ∩ "OB vs C" ∩ "VB vs C". Cluster analyses successfully clustered distinct expressions of BD. During gene ontology term enrichment analyses, categories with relevance to IL-8 production (MB vs C) and immune response to microorganisms (OB vs C) were differentially enriched. Distinct subsets of BD display distinct expression profiles and different disease associated pathways. Based on these clear discrepancies, the designation as "Behçet's syndrome" (BS) should be encouraged and future research should take into consideration the immunogenetic heterogeneity of BS subsets. Four gene groups, namely, negative regulators of inflammation (CD69, CLEC12A, CLEC12B, TNFAIP3), neutrophil granule proteins (LTF, OLFM4, AZU1, MMP8, DEFA4, CAMP), antigen processing and presentation proteins (CTSS, ERAP1), and regulators of immune response (LGALS2, BCL10, ITCH, CEACAM8, CD36, IL8, CCL4, EREG, NFKBIZ, CCR2, CD180, KLRC4, NFAT5) appear to be instrumental in BS immunopathogenesis.

Hyponatremia in the outpatient setting: clinical characteristics, risk factors, and outcome.

PURPOSE: Hyponatremia is a common disorder and hyponatremia in the outpatient setting is not extensively studied. Our aim was to investigate the characteristics of hyponatremia in ambulatory patients. METHODS: Seventy-six adult outpatients with hyponatremia were enrolled in this prospective study. Demographic features, presenting symptoms and signs, associating morbidities, medications, laboratory findings, mortalities, and length of hospital stay, were recorded. RESULTS: Mean age was 74.7 ± 12.7 years, and 52 (68.4 %) were female whereas 24 (31.6 %) were male. Mean sodium concentration was 123.6 ± 6.6 mEq/L. Leading cause was thiazide diuretic use (n = 37, 48.7 %) and approximately half of the patients (n = 40, 52.6 %) had a multifactorial etiology. Severe hyponatremia (sodium < 125 mEq/L) was identified in 37 (48.7 %). Thiazide diuretic use, vomiting, and apathy were independent predictors of severe hyponatremia. Eight (10.5 %) patients had a mortal course. A relatively younger age, male gender, presenting sign of lethargy, associating morbidities of malignancy, chronic liver disease, and hypoalbuminemia were risk factors for mortality. CONCLUSIONS: Hyponatremia is prevalent among elderly, especially in women and with thiazide diuretics. Apart from the trend toward sodium depletion observed in healthy elderly which occurs due to changes in the tubular handling of sodium, a multifactorial etiology including thiazides seems to predict the occurrence and the severity of hyponatremia. Hyponatremia may be a significant cause of mortality in seniors. A relatively younger age, male gender, association of cirrhosis, malignancy, and hypoalbuminemia predict mortality. In elderly outpatients, identification of the risk factors for hyponatremia and close monitoring are imperative to reduce the related mortality and morbidity.

Increased risk of contrast-induced acute kidney injury in patients with pulmonary thromboembolism.

INTRODUCTION: Computed tomography pulmonary angiography (CTPA) is currently an effective, reliable and widely employed diagnostic test for pulmonary thromboembolism (PT). PT harbors intrinsic clinical and biochemical abnormalities which may be associated with an increased risk of contrast-induced acute kidney injury (CIAKI). OBJECTIVES: To assess the incidence and risk factors of CIAKI among patients with PT diagnosed with CTPA. METHODS: One hundred and twenty-two consecutive patients who had been diagnosed with PT using CTPA between February 2006 and December 2010 were evaluated retrospectively. In addition to the classical risk factors of CIAKI, arterial blood gases, CTPA and transthoracic echocardiography findings of the patients were also recorded. RESULTS: The incidence of CIAKI was 13.1%. There were statistically important differences with respect to age, the presence of congestive heart failure (CHF), the use of angiotensin converting enzyme inhibitor-angiotensin II receptor blocker drugs (ACEI-ARB), the arterial blood pH (ABpH) and the length of hospitalization between the two groups of patients who developed (n:16) and did not develop (n:106) CIAKI. In the logistic regression analysis, age and ABpH were preserved in the final equation. CONCLUSION: The incidence of CIAKI among PT patients is significantly higher than the expected average. Older age, the presence of CHF, the use of ACEI-ARB, and additionally, low ABpH are important risk factors of CIAKI in patients with PT. Hypoxemia and low bicarbonate levels intrinsic to PT may contribute to the increased risk of CIAKI in this patient population and their correction may carry a prophylactic potential.

Nonsecretory Multiple Myeloma and AL Amyloidosis Presenting with Nephrotic Range Proteinuria.

Nonsecretory multiple myeloma (NSMM) is the absence of a detectable monoclonal protein in serum and urine of a multiple myeloma (MM) patient and immunoglobulin light chain (AL) amyloidosis is a significantly rare complication. A case of NSMM with AL amyloidosis and nephrotic range proteinuria is presented. Sharing clinical, therapeutic, and prognostic characteristics with MM, real challenge may be during initial diagnosis of NSMM and assessment of treatment response. In elderly patients with unexplained renal dysfunction, MM should be in the differential diagnosis and the absence of a monoclonal protein should not rule out MM but should remind us of the possibility of NSMM.

The Rarest of the Rare: Crossed Fused Renal Ectopia of the Superior Ectopia Type.

Crossed fused renal ectopia is a rare congenital anomaly of the urinary system where one kidney crosses over to opposite side and the parenchyma of the two kidneys fuse. Herein, we present an atypical CFRE case whose renal anatomy does not exactly match any of the already defined CFRE types. Both of the kidneys are ectopic with the crossed ectopic right kidney lying superiorly and fused to the upper pole of the left kidney. Renal arteries were originating from the common iliac arteries. A focal 90% stenosis was observed on the right main renal artery. The patient is borderline hypertensive.

Endothelial nitric oxide synthase gene intron 4 polymorphism predicts new onset diabetes mellitus after transplantation in kidney allograft recipients treated with cyclosporin A.

BACKGROUND: Nitric oxide (NO), synthesized from LS: -arginine by the enzyme endothelial nitric oxide synthase (eNOS), is a potent vasodilator and has been implicated in mediating insulin-induced uptake and metabolism of glucose in skeletal muscle. Polymorphisms of the eNOS gene have been associated with altered eNOS activity and NO levels. Although several factors have been demonstrated for new onset diabetes mellitus after transplantation (NODAT), determining a genetic susceptibility for all patients requires further study. In our study, we evaluated the relationship between eNOS gene intron 4 polymorphism and NODAT in kidney allograft recipients. METHODS: A total of 82 consecutive patients who received their first kidney transplantation and maintained graft function for at least a 12-month post-transplant period and who used triple therapy including cyclosporin A (CsA) for maintenance immunosuppression were included. PCR-RFLP was used for genetic analyses. RESULTS: Nine of 82 patients (11%) developed NODAT. Concerning the prevalence of eNOS intron 4 gene polymorphism, a significantly higher percentage of 4a allele carriers developed NODAT than non-carriers [6/26 (23.1%) versus 3/56 (5.4%), P = 0.02]. Compared with non-diabetics, NODAT patients were older (P = 0.04), had higher rate of hepatitis C (P < 0.05) and higher body mass index at the time of transplantation (P = 0.03). In regression analyses, having a 4a allele of the eNOS gene intron 4 polymorphism (P = 0.02) and HCV seropositivity (P = 0.03) were found to be independent risk factors for the development of NODAT. CONCLUSIONS: These findings suggest that carrying a 4a allele of the eNOS gene intron 4 polymorphism is associated with NODAT. This may help us to further understand the individual risk for development of NODAT in kidney allograft recipients under CsA treatment.

Acute renal infarction in a heavy smoker.

Renal infarction is a rare cause of acute abdominal and flank pain. Whether it occurs due to thrombosis or embolism, the occlusion of the renal arteries always results in renal infarction. Cigarette smoking is a known risk factor for arterial thrombosis. Both vasoconstrictor and pro-thrombotic effects of smoking lead to arterial thrombosis. Herein, we report a case of acute renal infarction in a heavy smoker. The definite diagnosis was made by contrast-enhanced abdominal computerized tomography and renal arteriography.

Renal tubular acidosis after kidney transplantation--incidence, risk factors and clinical implications.

BACKGROUND: Renal tubular acidosis (RTA) is a non-anion gap metabolic acidosis and is generally mild and asymptomatic in kidney recipients. Although calcineurin inhibitors, suboptimal allograft function, donor age and acute rejection have been associated with RTA, no detailed study has been conducted to investigate the prevalence and clinical implications of RTA in long-term kidney recipients. METHODS: In this cross-sectional study, we enrolled 109 patients (74 males, 35 females) for the study [patients with glomerular filtration rate (GFR) <30 ml/min/1.73 m(2), unstable allograft function, diarrhoea, and respiratory disease were excluded]. Thirty-six patients (33%) were found to have RTA on the basis of plasma bicarbonate, arterial pH, urine and serum anion gap measurements. RESULTS: Deceased donor transplantation [P = 0.034, 95% confidence interval (CI): 1.10-13.27], female gender (P = 0.017, 95% CI: 1.23-8.50), and lower GFR (55.8 +/- 19.4 in RTA and 66.1 +/- 15.9 ml/min/1.73 m(2) in non-RTA, P = 0.002, 95% CI: 1.10-13.27) were independent risk factors for RTA. Also, C-reactive protein was found to be higher in the RTA group (2.7 +/- 1.5 vs 2.0 +/- 1.5 mg/dl, P = 0.03), while no difference was noticed in body mass index or serum albumin. Analysis of the prevalence of osteoporosis and osteopenia in patients with RTA and without RTA, respectively, revealed no difference in frequency of osteoporosis (33% vs 31%) or osteopenia (33% vs 47%). CONCLUSION: Although long-term kidney recipients have a relatively high prevalence of RTA, it is usually mild and subclinical. Further studies are needed to clarify long-term effects of RTA in kidney recipients.

Pulmonary and peritoneal tuberculosis in a CAPD patient.

Patients with chronic renal failure have an increased incidence of tuberculosis due to decreased cellular immunity. More than half of the tuberculosis infection in these patients presented with extrapulmonary involvement. Tuberculous peritonitis is an important problem in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Simultaneous pulmonary and peritoneal tuberculosis is a very rare condition. We describe a 39-year-old man with culture negative CAPD peritonitis. In spite of conventional antimicrobial therapy the patient had persistent fever, weight loss, and night sweats. Approximately after one month from starting treatment, both sputum specimen and peritoneal fluid were positive for mycobacterium. Quadruple therapy for tuberculosis has been started. The response to treatment was promptly. He is still on treatment for six months and receiving CAPD. Tuberculous peritonitis should always be considered when patients on CAPD develop culture negative peritonitis treated with conventional antibiotics without improvement. In addition, the existence of extraperitoneal tuberculosis, especially pulmonary disease must be investigated.

The safety of gadolinium in patients with stage 3 and 4 renal failure.

BACKGROUND: Although there is a well-documented risk of acute renal failure (ARF) with the iodinated contrast agents, intravenous gadolinium-based contrast agents are considered non-nephrotoxic and have been widely used for magnetic resonance imaging (MRI). However, debate continues regarding the safety issue of gadolinium, especially in patients with kidney failure. Therefore, we aimed to evaluate the safety of gadolinium in patients with stage 3 and 4 renal failure as well as risk factors for nephrotoxicity. METHOD: We retrospectively analysed 473 patients with chronic renal failure who underwent angiographic MRI procedures in our centre from February 1999 to March 2005 in whom gadolinium was used as the sole contrast agent at a dose of 0.2 ml/kg. Among them, 91 patients with stage 3 or 4 renal failure according to K/DOQI definition, who had available data in their files, were enrolled in the study. The ARF was defined as an increase of at least 0.5 mg/dl in serum creatinine level over baseline after using gadolinium. RESULTS: Eleven of 91 (52 males, 39 females; median age 59 years; median estimated glomerular filtration rate (eGFR) 33 ml/min/1.73 m2) patients developed ARF (12.1%). The median eGFR was lower in patients with ARF than in those who did not develop ARF. The risk factors for ARF were baseline eGFR, older age, diabetic nephropathy and low baseline haemoglobin and albumin levels. Baseline eGFR and diabetic nephropathy were determined as the independent risk factors in regression analysis. CONCLUSIONS: An ARF can occur after gadolinium-based contrast agents in patients with moderate to severe chronic renal failure. Risk factors for ARF after gadolinium toxicity include diabetic nephropathy and low GFR.

Tamoxifen in the treatment of idiopathic retroperitoneal fibrosis.

Idiopathic retroperitoneal fibrosis (RF) is a histologically benign, nonspecific inflammatory process of the fibroadipose tissue in the retroperitoneum with an unknown etiology. It may be complicated due to encasement and obstruction of the retroperitoneal structures. Tamoxifen has been known to be an effective agent in regression of desmoid tumors which include similar mesenchymal elements to those seen in RF. Herein, we reported a case of RF presented with ureteral obstruction and acute renal failure. The patient was successfully treated with tamoxifen.

Minimal change nephrotic syndrome with stiff-person syndrome: is there a link?

Stiff-person syndrome is a rare, likely immune-mediated neurological disorder characterized by painful spasms and progressive symmetric rigidity of the axial and proximal limb muscles. Rigidity of truncal muscles and continuous contraction of the agonist and antagonist muscles caused by involuntary motor-unit firing at rest are the hallmarks of stiff-person syndrome. Immunosuppressive therapy has induced remission in patients with stiff-person syndrome. We report a patient with stiff-person syndrome with minimal change nephrotic syndrome (MCNS). The pathophysiologic states of stiff-person syndrome and MCNS are unclear. T-Cell-dependent mechanisms are highly suspected for the pathogenesis of both. The diagnosis of stiff-person syndrome was made on the basis of clinical and laboratory findings, and both MCNS and stiff-person syndrome resolved completely with immunosuppressive therapy. To our knowledge, this is the first case of stiff-person syndrome in association with MCNS in the literature.