Sim Kutlay

Randomized, crossover study of the effect of Vitamin C on EPO response in hemodialysis patients

BACKGROUND Vitamin C has been reported to be an effective adjuvant agent in the treatment of anemia in iron-overloaded hemodialysis patients. We aim to evaluate its effect on erythropoietin (EPO) response in a prospective, randomized, double-blind, crossover study. METHODS Sixty-three patients were randomly divided into two groups. Group 1 was treated with intravenous vitamin C, 500 mg, three times a week, and group 2, with placebo for 6 months. During the second 6-month period, group 1 was treated with placebo, and group 2, with the same dose of vitamin C. Thirty patients in group 1 and 28 patients in group 2 completed the study. Hemoglobin levels, weekly EPO dose, and ratio of EPO to hemoglobin as an index of EPO need were determined at both baseline and the end of the two periods, together with other parameters known to be associated with EPO response. RESULTS Twenty patients in group 1 (66.7%) and 18 patients in group 2 (64.3%) were responsive to vitamin C. In both groups, vitamin C resulted in a significant increase in hemoglobin levels (P < 0.0001 for both) and a significant decrease in EPO-hemoglobin ratio (P < 0.0001, P = 0.019). Transferrin saturation also increased with vitamin C treatment in both groups (P = 0.009, P = 0.005). All these parameters remained stable with placebo in both groups. Other parameters did not change throughout the study. CONCLUSION Vitamin C can be used as an effective adjuvant therapy to EPO in hemodialysis patients. Further studies are needed to determine possible predictors of hematologic response to vitamin C.

Assessment of left ventricular diastolic function with Doppler tissue imaging: Effects of preload and place of measurements

Mitral inflow velocities are widely used for the evaluation of left ventricular (LV) diastolic function. However, they are closely affected by other factors such as preload. The purpose of this study was to evaluate the usefulness of tissue Doppler velocities obtained from the mitral annulus for the evaluation of ventricular relaxation in patients under different loading conditions. We also evaluated the effect of preload at different sides on the mitral annulus. The study population consisted of 62 consecutive patients (38 male, 24 female with a mean age of 42 ± 13 years) who have undergone hemodialysis. Both mitral inflow velocities (E wave, A wave, E wave deceleration time and isovolumetric relaxation time) and mitral annulus tissue Doppler velocities (E′, A′) from the septal, lateral, anterior, posterolateral and inferior sides of the mitral annulus were measured immediately before and after hemodialysis. Mitral inflow E and A wave velocities and E/A ratio decreased significantly (p < 0.001, p = 0.007, p < 0.001, respectively) after hemodialysis. Mitral annulus E′ wave velocities and E′/A′ ratios obtained from five different sides of the annulus also changed significantly (p < 0.001 for all); however, there was no change in the A′ wave velocity (p > 0.05 for all) after hemodialysis. The decrease in E wave and E/A ratio in mitral inflow measurements and E′ velocities and E′/A′ ratios in tissue Doppler measurements were correlated with the amount of fluid extracted (for mitral inflow E wave, r = 0.392, p = 0.002 and E/A ratio, r = 0.280 and p = 0.027; for lateral side E′, r = 0.329, p = 0.009 and E′/A′ ratio, r = 0.286, p = 0.04; for septal side E′, r = 0.376, p = 0.003 and E′/A′ ratio, r = 0.297, p = 0.019; for anterior side E′, r = 0.342, p = 0.007 and E′/A′ ratio, r = 0.268, p = 0.035; for posterolateral side E′, r = 0.423, p = 0.001 and E′/A′ ratio, r = 0.343, p = 0.007; and for inferior side E′, r = 0.326, p = 0.01 and E′/A′ ratio, r = 0.278, p = 0.029). We conclude that mitral annular velocities obtained by tissue Doppler are preload dependent parameters for the evaluation of LV diastolic function.

Identification of patients at risk of acute rejection by pretransplantation and posttransplantation monitoring of soluble CD30 levels in kidney transplantation.

In this study, we investigated the impact of pre- and posttransplantation sCD30 monitoring on early (<6 months) acute rejection (AR) risk and analyzed the effect of different immunosuppressive regimens on posttransplantation sCD30 levels in kidney recipients. Fifty patients receiving kidney allograft and 10 healthy donors were included in this retrospective cohort study. Eight patients developed biopsy-proven AR (19%). In pretransplantation samples, patients showed a significantly higher sCD30 than healthy controls. The pretransplantation and posttransplantation (day-15) sCD30 levels were significantly elevated in rejecting patients compared to non-rejecting patients. No significant differences among immunosuppressive regimens were found in posttransplantation sCD30 levels. High pretransplantation and posttransplantation (day 15) sCD30 levels are associated with increased risk of early AR, and sCD30 can be another tool to evaluate immunological risk prior to kidney transplantation. There was no difference in immunosuppressive regimens used in this study on posttransplantation sCD30 levels at the first month.

RECOGNITION OF NEUROCOGNITIVE DYSFUNCTION IN CHRONIC HEMODIALYSIS PATIENTS

We sought to determine the prevalence, recognition, and consequences of mental impairment among chronic hemodialysis patients. We administered the Mini Mental Status Exam (MMSE), a brief validated method for assessing cognitive mental status that is commonly used by clinicians, to 84 patients from our dialysis units. To determine the clinical implications of mental impairment, we obtained Kt/V, albumin, protein catabolic rate, blood pressure, and hematocrit values. We found that 21% of subjects had mild mental impairment (MMSE 18 to 23) and that 11% had moderate-severe mental impairment (MMSE 0 to 17). We found no relationship between MMSE score and years on dialysis, Kt/V value, hematocrit value, or erythropoietin use. On univariate analysis, MMSE score was associated with albumin, protein catabolic rate, inter-dialytic weight gain, number of co-morbid conditions, number of hospitalizations. Outcomes on univariate analysis were further analyzed by multivariate analysis. There was an independent relationship between decrement in MMSE score and lower protein catabolic rate and increased hospitalization number and number of co-morbid conditions. Based on our findings, we recommend that clinicians routinely screen hemodialysis patients for mental impairment and target impaired patients for interventions to improve mental status and associated adverse outcomes.

Renal Doppler ultrasonographic findings in earthquake victims with crush injury.

In the Marmara earthquake, which occurred on August 17, 1999, 639 people had renal complications, and 477 needed hemodialysis treatment because of acute renal failure due to crush injury. Our objective was to use Doppler ultrasonography as a noninvasive procedure to provide renal hemodynamic information.

PREVALENCE OF CRYPTOSPORIDIUM INFECTION IN HEMODIALYSIS PATIENTS

The prevalence of Cryptosporidium infection in patients who are on chronic hemodialysis due to end-stage renal failure is investigated and compared with the incidence in the healthy population. Stool specimens of 74 adult hemodialysis patients treated on an outpatient basis and 50 healthy individuals are examined for Cryptosporidium oocysts by using the modified acid-fast method. While 20.27% (15/74) of patients in the dialysis group had Cryptosporidium oocysts in their stools, none (0/50) of the controls had such an infection (p < 0.001). Ten of 15 patients who had Cryptosporidium oocysts in their stool specimens were asymptomatic and the remaining 5 had diarrhea. Four of these 5 diarrheic patients had Cryptosporidium oocysts in their stools and 1 had both Cryptosporidium oocysts and Giardia trophozoites. Since hemodialysis patients with chronic renal failure are candidates for renal transplantation, general preventive measures against infection must be taken and these patients must be screened for their carrier state before transplantation.

The impact of daily sodium intake on posttransplant hypertension in kidney allograft recipients

BACKGROUND Hypertension (HT) is a common problem, observed frequently after kidney transplantation due to several causes. Posttransplantation HT increases the incidence of both cardiovascular diseases and allograft failure. Although a low sodium diet is strongly advised, the relationship between it and posttransplantation HT has not been well studied in transplant patients. METHODS Thirty-eight kidney transplant patients with stable allograft function ≥ 6 months after transplantation with a history of blood pressures ≥ 120/80 mm Hg despite antihypertensive therapy were included in this study. Office and ambulatory blood pressure monitoring (ABPM) were performed before the study. We measured serum biochemistries, hemograms, as well as 24-hour urinary excretions of sodium, potassium, calcium, magnesium, creatinine, and protein levels. After injection of low sodium diet of ≤ 80 mmol/d arranged by a dietician for 14 days, we repeated the measurements to compare the results. RESULTS After 14 days, the low sodium diet decreased the office systolic (from 132.4 ± 18.8 to 123.7 ± 13.4 mm Hg; P < .001) and diastolic (from 87.3 ± 10.8 to 81.3 ± 7.0 mm Hg; P < .001) blood pressures with decreased sodium excretion (from 177.2 ± 72.7 to 85.3 ± 37.7 mmol/L; P < .001) in the 24-hour urine. It also decreased the average systolic (from 125.3 ± 11.1 to 120.5 ± 9.1 mm Hg) and diastolic (from 80.7 ± 8.3 to 76.9 ± 6.6 mm Hg, P < .001) blood pressures in the 24-hour ABPM. Nighttime systolic (from 120.7 ± 10.9 to 113.9 ± 19.7 mm Hg) and diastolic (from 77.0 ± 9.4 to 74.1 ± 7.8 mm Hg) blood pressures by 24-hour ABPM were significantly decreased (P < .01; P < .05). The low sodium diet had no effect on dipper versus nondipper HT development. Although sodium, calcium, and magnesium excretions in the 24-hour urine were decreased, there was no change in potassium and protein excretion levels. CONCLUSIONS Daily sodium intake was extremely higher than recommended levels among kidney allograft recipients with HT. A low dietary sodium intake (80 mmol/d) combined with antihypertensive treatment controlled blood pressure efficiently by office and 24-hour ABPM readings.

Serum C-reactive Protein Level Is Associated with Renal Function and It Affects Echocardiographic Cardiovascular Disease in Pre-Dialysis Patients

Background: Relevance of serum CRP for morbidity and mortality in pre-dialysis patients has not been assessed extensively. The aim of this study was to determine the incidence of elevated serum CRP in pre-dialysis patients and to identify the factors that associate with serum CRP. We were also evaluated the effects of serum CRP on cardiovascular disease, anemia, and nutritional markers. Methods: One hundred and eight pre-dialysis patients with a mean creatinine clearance (CrCl) of 30.1 ml/min were included in the study. Data collected from each patient included demographics, co-morbidity, medications, blood pressures, blood biochemistry including serum CRP, renal function, and echocardiography. Results: Serum CRP was elevated (>5 mg/l) in 43 patients (39.8%). There was a negative correlation between serum CRP and CrCl (r = –0.370, p < 0.001). CrCl was the unique independent factor affecting serum CRP. Serum CRP was an independent factor affecting left ventricular mass index, fractional shortening, serum albumin and hematocrit in multivariate analyses. Conclusions: Prevalence of elevated serum CRP in pre-dialysis patients is high. Reduced renal clearance of CRP and/or cytokines may contribute to the inflammatory status. Elevated serum CRP is an important cause of morbidity in pre-dialysis patients.

Urinary Angiotensinogen Level Is Correlated with Proteinuria in Renal Transplant Recipients

OBJECTIVE Along with immunologic mechanisms, intrarenal renin-angiotensin system (RAS) activation has been suggested to play a role in the development and progression of chronic allograft injury. In various glomerular diseases, urinary angiotensinogen (AGT) level is a good indicator for the activation of intrarenal RAS. In this study, we aimed to investigate the parameters associated with urinary AGT level in patients with kidney transplantation. METHODS Seventy renal transplant patients with stable graft function (≥ 6 months after transplantation, serum creatinine level <2 mg/dL) and 21 healthy volunteers were included in the study. Patients were taking standard triple immunosuppressive treatment. Demographic characteristics of patients and healthy volunteers, drug use, and 24-hour ambulatory blood pressure measurements were recorded. Morning second urine and fasting blood samples were taken from all participants. Serum biochemical markers and urine Na, K, uric acid, creatinine, and protein levels were measured. Urinary AGT levels were determined by enzyme-linked immunosorbent assay. RESULTS Mean systolic and diastolic blood pressures in patients with renal transplantation were higher than in healthy volunteers. Both urinary AGT-urinary creatinine ratio (UAGT/UCr) and urinary protein-urinary creatinine ratio (UPro/UCr) were higher in kidney transplant patients than in healthy volunteers (P < .01; P < .0001; respectively). In patients with renal transplantation, UAGT/UCr was positively correlated with UPro/UCr and negatively correlated with estimated glomerular filtration rate (eGFR) (r = 0.738; P = .01; and r = -0.397; P = .01; respectively). There was no correlation between UAGT/UCr and other study parameters, including bood pressure levels. CONCLUSIONS Our findings indicate that high urinary excretion of AGT is associated with proteinuria and lower eGFR in kidney transplant recipients without overt chronic allograft injury. These preliminary results encourage us to design a long-term longitudinal analysis using urinary AGT along with multiple markers to obtain early diagnosis and to predict the prognosis of chronic allograft dysfunction.

Primary amyloidosis presenting with massive generalized lymphadenopathy

Systemic amyloidosis is an unusual cause of generalized massive lymphadenopathy. In such cases the clinical picture may mimic lymphoma. We report a case of generalized massive lymphadenopathy caused by amyloidosis. The 55-year old female patient was admitted to our hospital with dyspnea and edema in the lower extremities. These were diminished breath sounds with bilateral basal congestion hepatosplenomegaly and generalized massive lymphadenopathy in axillary, cervical, and inguinal areas. The diagnosis was made by excisional biopsy of one of the involved lymph nodes. Amyloidosis (AL type) was shown and treatment with melphalan and prednisone was initiated. Unfortunately the patient died after 51 days in hospital.