Case Report: A Novel Mutation Leading to 11-ß Hydroxylase Deficiency in a Female Patient.

BACKGROUND: 11ß hydroxylase deficiency (11ßOHD) ranks as the second most common enzyme deficiency that causes congenital adrenal hyperplasia. Depending on the severity of the enzyme deficiency, it can lead to cortisol deficiency, androgen excess and hypertension due to increased mineralocorticoid precursor levels. Many different types of mutations in the CYP11B1 gene located on chromosome 8q24.3 have been shown to cause 11ßOHD. Here, we report a novel missense mutation that leads to 11ßOHD in a female patient. CASE PRESENTATION: A 35-year-old female patient was admitted to the Endocrinology Department with a complaint of abdominal pain. The patient had a history of genital reconstruction surgery twice in childhood. On physical examination, an abdominal mass was detected. Laboratory examination of the patient revealed low levels of cortisol, potassium and high levels of ACTH, 11-deoxycortisol and androstenedione, suggesting 11ßOHD. Genotyping showed a novel homozygous missense mutation (c.1385T>C L462P variant) detected on the 8th chromosome where the CYP11B1 gene is located. Glucocorticoid therapy was commenced for the patient whose diagnosis of 11ßOHD was confirmed by both hormonal and genetic tests. A mass originating from the left adrenal gland with the largest diameter of 7 cm was compatible with myelolipoma. CONCLUSION: In this case report, we aimed to contribute to the literature by reporting a new missense mutation in the CYP11B1 gene, leading to classic type 11ßOHD that has not been described before.

Unexpected Late Response to Ofatumumab in Adult Post-Transplantation Recurrent Focal Segmental Glomerulosclerosis, Case Report.

BACKGROUND: Idiopathic focal segmental glomerulosclerosis is an important cause of kidney failure in adults, which is associated with a high risk of disease recurrence after transplantation. Plasmapheresis, rituximab, immunoadsorption, and high-dose cyclosporine are used to treat post-transplant recurrent focal segmental glomerulosclerosis (rFSGS). However, the response rate is variable, and few options remain for unresponsive patients. CASE REPORT: We present a 44-year-old man with an early post-transplant rFSGS. After peritransplant plasmapheresis, rituximab, and abatacept treatments failed, we employed ofatumumab. After 9 months without apparent benefit, we observed an unexpected partial remission thereafter, without severe side effects. Furthermore, remission has been sustained in 30-month follow-up. CONCLUSIONS: We believe ofatumumab can be considered an alternative for patients with plasmapheresis and rituximab-resistant post-transplant rFSGS.

Determination of Turkish norms of psychometric tests for diagnosing minimal hepatic encephalopathy and proposal of a high sensitive screening test battery.

BACKGROUND: Psychometric hepatic encephalopathy score (PHES) needs local standardization. AIMS: This study aimed at standardizing PHES for Turkish patients and compare them with German norms; to determine minimal hepatic encephalopathy (mHE) prevalence with two different methods [PHES battery and Critical Flicker Frequency (CFF)] and to assess whether sub-tests of the battery can be used for screening for mHE. METHODS: Healthy volunteers (n = 816; 400 male) and cirrhotics (n = 124; 58 male) were included. For mHE diagnosis PHES score threshold was set at ≤ - 5 points and that of CFF at < 39 Hz. For comparing German and Turkish norms, datasets were combined. Multiple backward procedure was applied to assess effects of age, sex and education on single tests of the battery. Receiver operating characteristic (ROC) curves were created for assessing diagnostic capabilities of subtests of the battery. RESULTS: PHES norms for Turks were developed. MHE prevalence in compensated cirrhotics was 29.8% and 27.4% with PHES and CFF tests, respectively, with low compatibility (kappa coefficient 0.389); mHE prevalence decreased to 16% when both tests were combined. Turks performed worse vs Germans in the digit symbol (DS) and serial dotting (SD) subtests but performed better in other subtests. In ROC analyzes of subtests, the combination of DS + SD tests achieved an AUROC of 0.974 versus PHES. CONCLUSIONS: Use of two methods for diagnosing mHE is important for research purposes. From a clinical perspective, sensitivity with acceptable specificity may suffice for screening instruments for mHE. Combined use of DS and SD subtests of the PHES battery appears suitable for this purpose.

A Comparison of the Indirect Calorimetry and Different Energy Equations for the Determination of Resting Energy Expenditure of Patients With Renal Transplantation.

OBJECTIVE: We aimed to evaluate the agreement between the resting energy expenditure (REE) obtained by indirect calorimetry and eight prediction equations in adult patients with renal transplantation and a newly developed REE prediction equation for use in patients with renal transplantation in the clinic. METHODS: A total of 51 patients (30 males and 21 females) were involved in the study. The REE was measured by indirect calorimetry and compared with the previous prediction equations. The agreement was assessed by the interclass correlation coefficient and by Bland-Altman plot analysis. RESULTS: No significant difference was found in terms of age and body mass index between the genders. Differences between the predicted and measured REEs were maximum in the Bernstein equation (-478 kcal) and minimum in the Cunningham equation (-69 kcal). It was found that underprediction values varied from 27.5% (chronic kidney disease equation) to 98.0% (Bernstein equation). The highest overprediction value was found in the Schofield equation (17.7%). The Cunningham equation and the new equation had the lowest root mean square error (265 kcal/day). In this study, fat-free mass (FFM) was found to be the most significant variable in multiple regression analysis (r2: 0.55). The new specific equation based on FFM was generated as 424.2 + 24.7∗FFM (kg). Besides that, it was found that the new equation and Cunningham equation were distributed randomly according to Bland-Altman analysis. A supplementary new equation based on available anthropometric measurements was developed as -1996.8 + 19.1∗height (cm) + 7.2∗body weight (kg). CONCLUSION: This study showed that most of the predictive equations significantly underestimated REE. In patients with renal transplantation, if the REE is not measurable by indirect calorimetry, the use of the proposed equations will be more accurate.

Can Helicobacter pylori Colonization Affect the Phosphate Binder Pill Burden in Dialysis Patients?

Phosphate binder pill (PBP) burden is a significant problem in dialysis patients. Phosphate absorption through the paracellular pathway increases in relatively acidic pH. In this study, we evaluated the effect of factors contributing to duodenal pH-Helicobacter pylori (HP), proton pump inhibitors (PPIs), and NaHCO3 capsules-on PBP burden. We evaluated 255 dialysis patients with gastric biopsies and excluded patients with low Kt/V, gastrectomy, and parathyroidectomy. Patients were divided into groups and subgroups regarding HP existence, use of PPI, or NaHCO3 capsules. HP+ group had significantly higher PBP burden and PBP equivalent doses (P < 0.001; both). HP+ subgroup not using daily PPIs or NaHCO3 capsules had the highest PBP burden and PBP equivalent doses (P < 0.001; both). HP- subgroups had similar PBP and PBP equivalent doses (P = 0.446 and P = 0.382; respectively). HP colonization might affect the PBP burden in dialysis patients due to a decrease of duodenal pH.

Evaluation of Clinical, Laboratory and Treatment Modalities in C3 Glomerulopathy: Single Center Experience.

BACKGROUND/AIM: C3 glomerulopathy (C3GP) defines a rare group of glomerulonephritis (GN), which could lead to end stage renal disease (ESRD). Histopathologic features of the disease have yet to be defined and the prognostic factors and optimal treatment are not fully known. The purpose of this study was to determine the demographic, histological change, treatment modalities and outcomes among patients with C3GP. MATERIAL AND METHOD: This retrospective observational study was conducted in the Department of Nephrology, Gazi University, Ankara, from 2013 to 2017. All patients with kidney biopsies fulfilling the criteria for C3GP were included in the study. RESULTS: Twenty-four patients with C3GP (50% male and of middle age - 43 years old) were enrolled in this study. 21% (5/24) patients developed ESRD. Renal biopsy findings such as crescent formation, glomerulo-sclerosis and tubular atrophy were similar in patients with ESRD, when compared to patients who did not develop ESRD. The treatment modalities of the patients were examined in two groups as MMF based and non-MMF based. The difference in the preservation of eGFR did not reach statistical significance between these two groups. The success rate of complete remission was similar between both groups. Serum creatinine levels >2.3 mg/dl at admission and need for renal replacement treatment (RRT) were associated with decreased renal survival. CONCLUSION: MMF based or non-MMF based treatments have similar efficacy in C3GP. Serum creatinine level higher than 2.3 mg/dl at the time of diagnosis and need for RRT during admission are a strong predictor of ESRD with high sensitivity and specificity.

Low Copeptin Levels in Patients With Intradialytic Hypotension.

Intradialytic hypotension (IDH) is related to high morbidity and mortality. There is evidence that arginine-vasopressin (AVP) responses could play a role. Copeptin is a reliable biomarker of AVP. In this study, copeptin, aldosterone, epinephrine, and norepinephrine levels in patients with IDH were evaluated throughout a hemodialysis (HD) session and compared with the control group. The study includes 15 patients who were normotensive during HD and 15 patients with IDH with a minimum HD vintage of 1 year. Blood samples were collected before the initiation of an HD session (T0 ), in the mid-session for control group, 30 min after mean arterial pressure drop for IDH patients (T1 ), and at the end of the session (T2 ). Groups had similar demographic features and health parameters, interdialytic weight gains, and ultrafiltration amounts. The IDH group had a mean arterial pressure decline of 39.9 (±6.4) mm Hg. Copeptin levels of the control group increased an average of 79.9 (±97.5) pmol/L at T1 and an additional 24.8 (±33.9) pmol/L at T2 . In the IDH group, copeptin level increases at T1 and T2 were 3.2 (±5.5) pmol/L and 34 (±44.6) pmol/L, respectively. Copeptin levels of the IDH group were significantly lower at T1 (P < 0.001) and at the T0 -T2 interval than control group (P = 0.05). In the control group, aldosterone levels distinctly decreased, and in the IDH group, aldosterone levels were elevated (P < 0.001). Small changes were detected in epinephrine and norepinephrine levels for both groups but did not reach significance (P = 0.6 and P = 0.3, respectively). Lower copeptin level alterations suggest inadequate AVP responses in patients with IDH.

Tenofovir-best hope for treatment of chronic hepatitis B infection?

BACKGROUND/AIMS: To evaluate the effectiveness of tenofovir in patients with chronic hepatitis B infection in a real life setting. MATERIALS AND METHODS: We performed a retrospective analysis of data from 164 patients with chronic hepatitis B who were treated with Tenofovir. Eighty-six patients (52.4%) were naïve. Seventy-seven (46.9%) patients were previously treated with anti-viral drugs, including standard interferon (n=4), pegylated (PEG) interferon (n=14), standard interferon together with lamivudine (n=13), lamivudine alone (n=41), adefovir (n=2), lamivudine together with adefovir (n=1), and entecavir (n=2). Six patients (3.7%) had liver cirrhosis before treatment of tenofovir. RESULTS: The patients who have hepatitis B viral DNA>104 copy/mL with chronic hepatitis B infection were included in the treatment of Tenofovir. Average follow up time was 30.31±14.33 months. HBV DNA negativity and alanine aminotransferase (ALT) normalization were 86.5% and 71.3%, respectively, at the last visit. Hepatitis B e-Antigen (HBeAg) seroconversion occurred in 11 (19.6%) out of 164 patients. During the follow-up period, 4 (2.4%) patients developed liver cirrhosis and in 5 (3%) patients hepatocellular carcinoma (HCC) occurred out of 164 patients. HBsAg seroconversion occurred in one patient (0.6%). CONCLUSION: Tenofovir can be used safely and successfully in those patients that were naive, experienced with immune modulators and/or antivirals, HBeAg-positive, and HBeAg-negative patients.