Rahmi Yilmaz

Interferon Therapy for Acute Hepatitis C during Pregnancy

OBJECTIVE: Due to their antiproliferative activity, the probable effects of interferons on a fetus are a concern. We report on a pregnant patient who developed acute hepatitis C during pregnancy and was treated with a short course of interferon alfa therapy with a successful outcome. CASE SUMMARY: A 26-year-old woman was diagnosed with acute hepatitis C at the 16th week of pregnancy. She received a total dose of 72 million units of interferon alfa-2b during a 2 1/2 month period. Although the therapy was discontinued due to adverse effects, a complete biochemical and virologic response was obtained. Premature labor occurred and healthy, but growth-restricted, twin infants were born transvaginally. At 18 months of age, they had normal development, with a negative hepatitis C serology. DISCUSSION: The rate of transmission of hepatitis C virus from mother to infant is within the range of 1–5%. Although acute hepatitis C during pregnancy is a very rare occurrence, the mother is at a great risk for chronic infection. There is scarce literature about the probable effects of interferon use during pregnancy due to a lack of controlled studies in this special population. A total of 8 infants, including ours, exposed to interferon alfa and/or ribavirin during pregnancy showed no congenital anomalies or malformations. CONCLUSIONS: Patients with chronic hepatitis whose therapy can be delayed should not be treated with interferon due to a lack of controlled studies. However, women exposed to interferon inadvertently during pregnancy may be encouraged to continue pregnancy. In patients with acute hepatitis C during pregnancy, the use of interferon therapy should be considered with close monitoring.

A rare complication of hemodialysis catheters: Superior vena cava syndrome

Central venous catheters in hemodialysis patients may result in superior vena cava (SVC) syndrome. With the increasing use of these catheters, the SVC syndrome will probably be more common among hemodialysis patients. This report describes 3 cases of SVC syndrome due to central venous catheters that developed in hemodialysis patients with previous multiple catheter placements.

Major Barriers against Renin–Angiotensin–Aldosterone System Blocker Use in Chronic Kidney Disease Stages 3–5 in Clinical Practice: A Safety Concern?

Renin–angiotensin–aldosterone system (RAAS) blockers are underutilized in patients with chronic kidney disease (CKD). We aimed to determine barriers against the use of RAAS blockers in these patients. Patients with stage 3–5 CKD referred to Hacettepe University Hospital Nephrology Unit during a 1 year period were evaluated for RAAS blocker use. Two hundred and seventy-nine patients (166 male, 113 female) were analyzed. The mean age of the patients was 56.7 ± 15.2 years, mean serum creatinine was 2.45 ± 1.44 mg/dL, and mean glomerular filtration rate was 33.3 ± 15.1 mL/min. The mean follow-up time was 22.0 ± 21.9 months and the clinical visit number was 4.0 ± 3.5. Angiotensin-converting-enzyme inhibitors or angiotensin receptor blockers were used by 68.8% of all patients and 67.7% of diabetic patients at the time of analysis. In 82.1% of patients, RAAS blockers had either been used earlier or were being used. Hyperkalemia was the principal reason for both not starting and also discontinuing these drugs in patients with CKD. In 37.4% of patients, reasons for not starting RAAS blockers were unclear. This study showed that hyperkalemia is the major barrier against the use of RAAS blockers in patients with CKD. There was, however, a subset of patients who did not receive RAAS blockers even without clear contraindications.

Utility of the Doppler ultrasound parameter, resistive index, in renal transplant histopathology.

BACKGROUND Doppler ultrasonography is routinely used by many clinicians during long-term follow-up to identify high-risk patients without diagnosing the exact cause of graft dysfunction. Despite a number of studies showing a correlation between intrarenal resistive index (RI) and renal function in patients with kidney diseases, correlations between RI and renal histopathologic characteristics have not been sufficiently evaluated in renal transplant recipients. The aim of this study was to examine this relationship in grafted kidneys. PATIENTS AND METHODS The intrarenal RI was retrospectively compared with biopsy findings in 28 kidney recipients. All renal biopsy specimens were reviewed by light microscopy and immunofluorescence staining. For glomerulosclerosis, we considered the percentage of glomeruli showing this change; for interstitial fibrosis/tubular atrophy and interstitial infiltration, we graded abnormalities according to the methods of Kliem et al (Kidney Int 49:666, 1996). RESULTS The percentage of globally sclerosed glomeruli was significantly greater among patients with RI values higher than 0.75 than below this level (23% vs 47%; P = .022). Patients with grade 1 interstitial fibrosis and tubular atrophy (n = 14) showed lower RI values (0.68 +/- 0.03 vs 0.74 +/- 0.06; P = .047) than those with grade 3 fibrosis (n = 12). Similarly, lower RI values (0.66 +/- 0.02 vs 0.73 +/- 0.05; P = .014) were observed among patients with grade 1 (n = 13) compared with grade 3 interstitial infiltration (n = 13). CONCLUSION RI seemed to provide a prognostic marker for the graft rather than yielding an exact diagnosis of renal graft dysfunction.

Daily Sodium Intake in Chronic Kidney Disease Patients during Nephrology Clinic Follow-Up: An Observational Study with 24-Hour Urine Sodium Measurement

Objective: To determine daily sodium intake in ‘real practice’ in a large group of chronic kidney disease (CKD) patients who were under regular follow-up in a nephrology clinic. Methods: A total of 373 consecutive outpatients with CKD stages 1–5 (not on dialysis; men: 52.3%, mean age: 51.6 ± 15.4 years) were included in the study. All patients had at least 3 or more nephrology visits and received information on reducing their sodium intake. Data for systolic and diastolic blood pressure, number of antihypertensive medications and 2 consecutive 24-hour urinary sodium levels were obtained from the patients’ medical records. Results: The mean 24-hour urinary sodium levels of 2 consecutive urine samples were 168.8 ± 70.3 and 169.3 ± 67.4 mEq/day (p > 0.05). Only 14.7% of the patients had a sodium excretion <100 mmol/day. There was no difference in daily sodium intake from stages 1 to 4, but it was significantly lower in stage 5 (126.6 ± 60.5 mEq/day, p < 0.05). No relation was found between 24-hour urinary sodium output, number of antihypertensives or thiazide use. Conclusions: This study showed that almost 85% of CKD patients under regular nephrologic care were consuming more sodium than the recommended level. More robust measures should be devised to increase patient and physician compliance with reducing sodium intake in CKD.

Acute kidney injury in the elderly population

The elderly population is more prone to acute kidney injury (AKI) than younger populations. Older patients have less renal reserve because of reduced glomerular filtration rates due to anatomic/functional changes, and concomitant diseases such as hypertension, diabetes, atherosclerosis, heart failure, ischemic renal disease, and obstructive uropathy. The risk of AKI may also increase as a result of aggressive diagnostic and therapeutic procedures, which include medical agents, radiology, and surgical intervention. AKI in the elderly has a multifactorial physiopathology due to different etiologies. Studies that have specifically compared prognosis of AKI in elderly versus young over the recent years suggest that age is a predictor of long-term outcome. In most cases, the treatment of AKI is similar for all age groups. The majority of critically ill patients with AKI will eventually need renal replacement therapy (RRT). The influence of RRT on renal outcome remains a subject of intense investigation and debate. Avoiding situations that could damage the kidney is an important strategy to prevent AKI development in the elderly, besides medical and interventional therapeutics.

Use of Mesenchymal Stem Cells and Darbepoetin Improve Ischemia-Induced Acute Kidney Injury Outcomes

Background: Interest has recently been focused on the possible role of bone marrow-originating stem cells and the therapeutic role of erythropoietin in the recovery of ischemia-induced acute kidney injury (AKI). The aim of the present study was to compare treatment with mesenchymal stem cells (MSCs) to treatment with darbepoetin-α (DPO) or both concomitantly in a rat model of ischemia/reperfusion (I/R) AKI. Methods: Forty male Sprague-Dawley rats were included, and 28 of them were randomly assigned to controls (treated with serum physiologic) or one of the three treatment groups treated with either DPO, MSCs, or both (MSCs and DPO concomitantly) after the induction of I/R injury. Hematocrit, serum creatinine, and BUN levels were obtained at 0, 24, 48, and 72 h of surgery, and renal tissue was obtained at 72 h after nephrectomy for histological analysis. Tissue injury was quantified by standardized histological scoring systems, using light and electron microscopes. Results: Treatment with MSCs or DPO improved renal function compared with controls. However, the improvement observed in renal function in the MSC/DPO group was better than that in the other groups. Histological analysis demonstrated that tissue injury was significantly decreased in rats in the MSC or DPO groups compared to that of the controls; however the best recovery was observed in rats treated with MSCs and DPO concomitantly. Conclusion: These results suggest that concomitant application of DPO and MSCs may be a potential novel renoprotective therapy for patients after having sustained an ischemic renal insult.

Gingival health status in renal transplant recipients: relationship between systemic inflammation and atherosclerosis

Cardiovascular disease (CVD) is the leading cause of mortality in renal transplant recipients (RTR). Systemic and periodontal inflammation has been suggested to have a possible role in the development of atherosclerosis. In the present study, we aimed to investigate the relationship between gingival health status, inflammation and atherosclerosis in RTRs. Eighty‐three RTR (50 male, 33 female) were enrolled in the study. Routine biochemical analyses, serum lipoproteins, C‐reactive protein, fibrinogen, homocystein, parathyroid hormone (PTH) and cyclosporin A (CsA) trough levels were studied. All patients had 24‐h ambulatory blood pressure monitoring and B‐mode ultrasound of the common carotid arteries. Gingival status was evaluated by the Löe and Silness gingival index (GI). Mean GI value was 2.3 ± 0.5. Fifty patients (60.3%) had GI value ≥ 2.1 (severe gingivitis; group A). Thirty‐three patients (39.7%) had GI value < 2.1 (no or moderate gingivitis; group B). Age, carotid intima‐media thickness (CIMT) and mean time on dialysis before transplantation were significantly higher in group A than in B. Systemic inflammation markers were not different between group A and group B. Mean CIMT was positively correlated with GI (r = 0.425; p = 0.001) and negatively correlated with high‐density lipoprotein cholesterol (r = −0.256; p = 0.023). After the correction for confounding variables, mean CIMT was still significantly correlated with GI (r = 0.376, p = 0.02). In RTR, gingival inflammation seems to be associated with CIMT in the absence of systemic inflammation. Thus, gingivitis may, in part, play a role in the development of systemic atherosclerosis without causing any aggravation in systemic inflammatory response.

Impact of amlodipine or ramipril treatment on left ventricular mass and carotid intima-media thickness in nondiabetic hemodialysis patients

Objective: Left ventricular hypertrophy (LVH) and atherosclerosis are frequently observed in uremic patients and they have appeared as an independent predictor of cardiovascular morbidity and mortality. The aim of this study was to compare the effects of ramipril and amlodipine on left ventricular mass index (LVMI) and carotid intima-media thickness (CIMT) in nondiabetic hypertensive hemodialysis patients. Methods: A total of 112 hemodialysis (HD) patients were included in this study. Patients were randomly allocated to receive ramipril or amlodipine for 1 year. Blood pressure (BP) measurements, LVMI, and CIMT were assessed at baseline and 6-month intervals. Biochemical parameters and inflammatory markers were also determined at the initiation and during the study period. Results: Similar BP decrease was observed in treatment groups. During follow-up, LVMI and CIMT progressed likewise in both treatment groups despite BP control. However, subgrouping analyses due to the pattern of left ventricular geometry showed that LVMI in patients with eccentric LVH increased, whereas LVMI decreased in subjects with concentric LVH under antihypertensive treatment. Discussion: BP control with ramipril or amlodipine could not provide adequate protection for development or progression of atherosclerosis and eccentric type of LVH in nondiabetic HD patients.

A Novel Immunosuppressive Agent, Sirolimus, in the Treatment of Kaposi's Sarcoma in a Renal Transplant Recipient

Renal transplant recipients are susceptible to Kaposis sarcoma (KS) because of treatment with immunosuppressive drugs. Sirolimus, a new immunosuppressive agent, has been successfully used for immune-suppression in kidney transplant recipients. Several studies have shown the potential role of sirolimus to inhibit progression of KS in kidney-transplant recipients. This report details a kidney-transplant recipient with cutaneous KS who had a complete remission in response to sirolimus therapy.