Can eculizumab be an option in traditional treatment-resistant ulcerative colitis?

Atypical/complement-mediated hemolytic uremic syndrome (A-HUS/CM-HUS) is a hereditary or sporadic disease with thrombotic microangiopathy (TMA). Diarrhea is a trigger that can cause attacks of CM-HUS. Although there are opinions that complement system activation plays a role in intestinal inflammation in patients with inflammatory bowel disease, the association of TMA with inflammatory bowel disease (IBD) has rarely been reported. In our case, a CM-HUS case that developed without an additional triggering factor in the course of ulcerative colitis (UC) was successfully treated with eculizumab, and then UC remission was also achieved. In this context, we would like to point out that the irregularities in the alternative pathway of the complement system may cause clinical findings in extra-renal organs, and the complement system may also play a role in the pathogenesis of inflammatory bowel disease. In addition, we think that our case may guide further studies on the usability of anti-complement therapies in treating patients with IBD who are resistant to conventional treatments.

Acute kidney injury in Turkey: epidemiological characteristics, etiology, clinical course, and prognosis.

BACKGROUND: This study aimed to evaluate the etiologies, comorbidities, and outcomes of acute kidney injury (AKI) in Turkey and determine any potential differences among different geographical parts of the country. METHODS: This prospective observational study was conducted by the Acute Kidney Injury Working Group of the Turkish Society of Nephrology. Demographical and clinical data of patients with AKI at the time of diagnosis and at the 1st week and 1st, 3rd, and 6th months of diagnosis were evaluated to determine patient and renal survival and factors associated with patient prognosis. RESULTS: A total of 776 patients were included (54.7% male, median age: 67 years). Prerenal etiologies, including dehydration, heart failure, and sepsis, were more frequent than other etiologies. 58.9% of the patients had at least one renal etiology, with nephrotoxic agent exposure as the most common etiology. The etiologic factors were mostly similar throughout the country. 33.6% of the patients needed kidney replacement therapy. At the 6th month of diagnosis, 29.5% of the patients had complete recovery; 34.1% had partial recovery; 9.5% developed end-stage kidney disease; and 24.1% died. The mortality rate was higher in the patients from the Eastern Anatolian region; those admitted to the intensive care unit; those with prerenal, renal, and postrenal etiologies together, stage 3 AKI, sepsis, cirrhosis, heart failure, and malignancy; those who need kidney replacement therapy; and those without chronic kidney disease than in the other patients. CONCLUSION: Physicians managing patients with AKI should be alert against dehydration, heart failure, sepsis, and nephrotoxic agent exposure. Understanding the characteristics and outcomes of patients with AKI in their countries would help prevent AKI and improve treatment strategies.

The Prevalence of Fabry Disease in Patients with Chronic Kidney Disease in Turkey: The TURKFAB Study.

BACKGROUND/AIMS: Fabry disease is a treatable cause of chronic kidney disease (CKD) characterized by a genetic deficiency of α-galactosidase A. European Renal Best Practice (ERBP) recommends screening for Fabry disease in CKD patients. However, this is based on expert opinion and there are no reports of the prevalence of Fabry disease in stage 1-5 CKD. Hence, we investigated the prevalence of Fabry disease in CKD patients not receiving renal replacement therapy. METHODS: This prospective study assessed α-galactosidase activity in dried blood spots in 313 stage 1-5 CKD patients, 167 males, between ages of 18-70 years whose etiology of CKD was unknown and were not receiving renal replacement therapy. The diagnosis was confirmed by GLA gene mutation analysis. RESULTS: Three (all males) of 313 CKD patients (0.95%) were diagnosed of Fabry disease, for a prevalence in males of 1.80%. Family screening identified 8 aditional Fabry patients with CKD. Of a total of 11 Fabry patients, 7 were male and started enzyme replacement therapy and 4 were female. The most frequent manifestations in male patients were fatigue (100%), tinnitus, vertigo, acroparesthesia, hypohidrosis, cornea verticillata and angiokeratoma (all 85%), heat intolerance (71%), and abdominal pain (57%). The most frequent manifestations in female patients were fatigue and cornea verticillata (50%), and tinnitus, vertigo and angiokeratoma (25%). Three patients had severe episodic abdominal pain attacks and proteinuria, and were misdiagnosed as familial Mediterranean fever. CONCLUSIONS: The prevalence of Fabry disease in selected CKD patients is in the range found among renal replacement therapy patients, but the disease is diagnosed at an earlier, treatable stage. These data support the ERBP recommendation to screen for Fabry disease in patients with CKD of unknown origin.

Drug Dose Adjustment in Dialysis Patients Admitted in Clinics Other Than Internal Medicine.

Many drugs that are administered during hospitalization are metabolized or excreted through kidneys, consequently require dosage adjustment. We aimed to investigate inappropriate prescription of drugs requiring renal dose adjustment (RDA) in various surgical and medical inpatient clinics. We retrospectively determined dialysis patients hospitalized between January 2007 and December 2010. Inpatient clinics, including cardiology, pulmonary medicine, neurology, infectious diseases (medical clinics) and cardiovascular surgery, orthopedics, general surgery, obstetrics and gynecology, and neurosurgery (surgical clinics), were screened via electronic database. Total and RDA medications were determined. RDA drugs correctly adjusted to creatinine clearance were labeled as RDA-A (appropriate), otherwise as RDA-I (inappropriate). Renal doses of RDA medications were based on the "American College of Physicians Drug Prescribing in Renal Failure, fifth Edition." Two hundred seventeen hospitalization records of 172 dialysis patients (92 men and 80 women) were included in the analysis. Mean age of patients was 59.4 ± 14.6 years, and the mean hospitalization duration was 8.5 ± 7.8 days. In total, 247 (84.3%, percentage in drugs requiring dose adjustment) and 175 (46.2%) drugs have been inadequately dosed in surgical and medical clinics, respectively. The percentage of patients to whom at least 1 RDA-I drug was ordered was 92% and 91.4% for surgical and medical clinics, respectively (P > 0.05). Nephrology consultation numbers were 8 (7.1%) in surgical and 32 (30.4%) in medical clinics. The most common RDA-I drugs were aspirin and famotidine. A significant portion of RDA drugs was ordered inappropriately both in surgical and medical clinics. Nephrology consultation rate was very low. Measures to increase physician awareness are required to improve results.

Serum neutrophil gelatinase-associated lipocalin is associated with cardiovascular events in patients with chronic kidney disease.

BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) is a member of the lipocalin family best known as a novel and early marker of acute kidney injury (AKI). Recent data suggest that NGQueryAL is not only a marker of AKI, but also an important player in the vascular remodeling, atherosclerotic plaque stability and thrombus formation. We conducted this study to investigate the association of serum NGAL levels with fatal and composite (fatal and non-fatal) cardiovascular events (CVE) in a cohort of patients with stage 1-5 CKD. METHODS: This was an observational cohort study in which serum NGAL was obtained from 298 CKD (stages 1-5) patients. Fatal and composite CVE were recorded for a median 41 months. We examined alteration of serum NGAL through CKD groups as well as association with inflammatory markers. We also performed a Cox regression analysis to determine the association of NGAL with predefined clinical outcomes. RESULTS: The median value of NGAL was 50.5 ng/mL (IR 47.6-54.9 ng/mL), and higher NGAL values were recorded in diabetic patients. In a multiple linear regression model, including all univariate associates of NGAL, only log eGFR, log hs-CRP and log HDL cholesterol maintained an independent association with log NGAL. During the observational period, 30 patients died due to cardiovascular causes and 69 non-fatal CVE were registered. In the fully adjusted model, we observed a 2.08-fold increase in the risk of fatal CVE and a 1.50-fold increase in the risk of fatal and non-fatal CVE for each increment of 1 SD in log NGAL values. CONCLUSIONS: This is the first study that shows that serum NGAL is associated with cardiovascular events (fatal and non-fatal) in patients with CKD, independently of traditional risk factors, renal function and inflammation.

Serum uric acid may predict development of progressive acute kidney injury after open heart surgery.

OBJECTIVES: Acute kidney injury (AKI) is a common complication of cardiac surgery developing in 25-35% cases. Recently, neutrophil gelatinase-associated lipocalin (NGAL) was shown to predict AKI development earlier than serum creatinine. Some studies demonstrated the predictive role of post-operative serum uric acid (SUA) as an early marker of AKI. We aimed to study the role of serum and urine NGAL as well as SUA to predict progression of AKI. DESIGN AND METHODS: This is a prospective observational study of patients undergoing cardiac surgery. Blood and urine samples for measurement of uric acid, serum and urine NGAL levels were collected prior to cardiac surgery (0 h), and in the time course at 2nd and 24th hours after surgery. Patients who developed AKI were divided into two subgroups as progressing and non-progressing AKI. RESULTS: Sixty patients (42 males, 18 females) were included. After cardiac surgery, 40 patients developed AKI, 20 of whom non-progressing AKI, and 20 progressing AKI. All of the markers significantly increased in AKI patients. A receiver operator characteristics (ROC) curve analysis showed higher predictive ability of SUA for progressing AKI compared with serum and urine NGAL. When compared markers obtained at the second hour after surgery, UA had significantly large AUC than NGAL to predict AKI developed at 24 and 48 h, particularly in patients, who require renal replacement therapy (RRT). CONCLUSION: Uric acid seems to predict the progression of AKI and RRT requirement in patients underwent cardiac surgery better than NGAL.

Soluble TWEAK independently predicts atherosclerosis in renal transplant patients.

BACKGROUND: Cardiovascular risk is increased in the early stages of chronic kidney disease (CKD) and also found to be ongoing in renal transplant (Rtx) patients. As a sign of atherosclerosis, increased carotid intima-media thickness (CIMT) has been widely accepted as a strong predictor of cardiovascular disease (CVD) and mortality in CKD patients. A novel markers, soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) and neutrophil-to-lymphocyte ratio (NLR) were introduced as potential markers in inflammatory disorders including CKD. The role of Rtx in terms of atherogenesis is still unclear. We aimed to investigate the relationship between sTWEAK, NLR and CIMT in Rtx patients without overt CVD and to compare these results with those obtained from healthy subjects. METHODS: Cross-sectional analysis in which CIMT measurements, NLR and serum TWEAK levels were assessed in 70 Rtx patients (29 females; mean age, 40.6 ± 12.4 years) and 25 healthy subjects (13 females, mean age; 37.4±8.8 years). RESULTS: sTWEAK levels were significantly decreased (p=0.01) and hs-CRP, NLR and CIMT levels of Rtx patients were significantly increased compared to healthy subjects (p<0.0001, p=0.001, p<0.0001, respectively). sTWEAK was also found to be decreased when eGFR was decreased (p=0.04 between all groups). CIMT was positively correlated with sTWEAK and NLR in Rtx patients (r=0.81, p<0.0001 and r=0.33, p=0.006, respectively). sTWEAK was also positively correlated with NLR (r=0.37, p=0.002). In the multivariate analysis only sTWEAK was found to be an independent variable of increased CIMT. CONCLUSION: sTWEAK might have a role in the pathogenesis of ongoing atherosclerosis in Rtx patients.

Peri-aortic fat tissue thickness in peritoneal dialysis patients.

BACKGROUND: Thoracic peri-aortic fat tissue (PFT) and epicardial adipose tissue (EAT) are metabolically active visceral fat deposits surrounding the thoracic aorta and the heart, respectively. Various studies have demonstrated a positive predictive value of both PFT and EAT for coronary artery disease in the general population. In the present study, we aimed to investigate PFT thickness and the independent predictors of PFT in peritoneal dialysis (PD) patients. ♢ METHODS: Our cross-sectional study enrolled 35 PD patients (10 women, 25 men) and 30 age-and-sex-matched healthy subjects (15 women, 15 men). We measured PFT, thoracic artery calcification (TAC), EAT, and coronary artery calcification (CAC) by electrocardiogram-gated 64-multi-detector computed tomography. ♢ RESULTS: The measured PFT, EAT, CAC, and TAC were significantly higher in the PD group than in the healthy subjects (p < 0.05 each). In the PD group, PFT and TAC were significantly correlated (r = 0.33, p = 0.007). Also, PFT measurements were positively correlated with EAT and total CAC in the PD and the control group alike (r = 0.58, p = 0.001 and r = 0.54, p = 0.01 respectively). A stepwise linear regression analysis revealed that age, duration of hypertension, and being a PD patient were independent predictors of PFT. ♢ CONCLUSIONS: Measured PFT was higher in PD patients than in healthy subjects and, in the PD population, was also shown to be related to calcification scores and EAT.

Effects of secondary amyloidosis on arteriovenous hemodialysis fistula outcomes and intradialytic hypotension: a case-control study.

Amyloid fibrils can affect vascular structure through deposition and by causing nitric oxide depletion and increase of asymmetric dimethyl arginine. Patients with amyloidosis are prone to development of hypotension. Hypotension may also affect the maturation of arteriovenous fistula (AVF) and may set the stage for formation of thrombosis and fistula failure. Thus, we aimed to evaluate effects of secondary amyloidosis on AVF outcomes and intradialytic hypotension. This is a case-control study which included 20 hemodialysis patients with amyloidosis and 20 hemodialysis patients without amyloidosis as control group. All patients underwent Doppler ultrasound of AVF. A thorough fistula history and baseline laboratory values along with episodes of intradialytic hypotension and blood pressure measurements were recorded. There was no difference between the groups regarding age, gender, body mass index, presence of comorbidities, hypertension, and drug use. Systolic and diastolic blood pressures were similar (119 ± 28/75 ± 17 and 120 ± 14/75 ± 10 mmHg for patients with and without amyloidosis, respectively). Intradialytic hypotension episodes were also similar. Patients with amyloidosis had significantly lower serum albumin and higher C-reactive protein values compared to control hemodialysis patients. AVF sites and total number of created fistulas were similar in both groups. Flow rates of current functional AVFs were not different between the groups (1084 ± 875 and 845 ± 466 mL/minute for patients with and without amyloidosis, respectively, p:0.67). Patency duration of first AVF was not different between the groups. Clinical fistula outcomes and rate of intradialytic hypotension episodes were not significantly different between patients with and without secondary systemic amyloidosis.

The relationship between neutrophil-to-lymphocyte ratio and inflammation in end-stage renal disease patients.

BACKGROUND: Patients with end-stage renal disease (ESRD) have elevated serum levels of inflammatory mediators including C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukin (IL)-6. Systemic inflammation was found to be correlated with coronary artery disease (CAD) in this population. Neutrophil-to-lymphocyte ratio (NLR) was introduced as a potential marker to determine inflammation in cardiac and non-cardiac disorders. Data regarding NLR and its association with inflammation are lacking. We aimed to determine the relationship between NLR and inflammation in ESRD patients. MATERIAL AND METHODS: This was a cross-sectional study involving 61 ESRD patients (25 females and 36 males; mean age: 48.3 ± 14.5 years) receiving peritoneal dialysis (PD) or hemodialysis (HD) for ≥6 months in the Dialysis Unit of Selcuk University. NLR, CRP, TNF-α, and IL-6 levels were measured. RESULTS: NLR, serum CRP, IL-6, and TNF-α levels were significantly higher in PD patients when compared with HD patients. ESRD patients with NLR ≥ 3.5 had significantly higher TNF-α levels when compared with patients with NLR < 3.5. In the bivariate correlation analysis, NLR was positively correlated with TNF-α in this population. CONCLUSIONS: Simple calculation of NLR can predict inflammation in ESRD patients.

Uncontrolled hypertension secondary to leukemic cell infiltration of kidneys in a hemodialysis patient.

Leukemic infiltration of the kidney is usually silent, and the admission of the patients with renal dysfunction or acute kidney injury is uncommon. We present a 34-year old hemodialysis patient with new onset of uncontrolled hypertension, erythropoietin-resistant anemia, thrombocytopenia, and Bell's palsy. On admission, his blood pressure (BP) was 210/110 mmHg and he had petechiae and purpura at upper and lower extremities. Renal ultrasonography (USG) showed bilaterally enlarged kidneys without hydronephrosis, unlike his previous USG, which determined bilaterally atrophic kidneys. Acute lymphoblastic leukemia, hypertensive crisis due to bilateral leukemic cell infiltration of kidneys, tumor lysis syndrome, and leukemic involvement of the facial nerve were diagnosed. Despite intense antihypertensive management, his BP was not controlled. After prednisolone, daunorubicine, and vincristine therapy, the size of kidneys diminished and his BP dropped under normal range. In conclusion, pathological findings such as uncontrolled hypertension, flank pain, skin rashes, and abnormal blood count should be considered carefully, even in patients with end-stage renal disease receiving renal replacement therapy.