Ibrahim Karayaylali

Bone mineral density and its correlation with clinical and laboratory factors in chronic peritoneal dialysis patients

The aim of this study was to assess the clinical and laboratory correlations of bone mineral density (BMD) measurements among a large population of patients on chronic peritoneal dialysis (PD). This cross-sectional, multicenter study was carried out in 292 PD patients with a mean age of 56 ± 16 years and mean duration of PD 3.1 ± 2.1 years. Altogether, 129 female and 163 male patients from 24 centers in Canada, Greece, and Turkey were included in the study. BMD findings, obtained by dual-energy X-ray absorptiometry (DEXA) and some other major clinical and laboratory indices of bone mineral deposition as well as uremic osteodystrophy were investigated. In the 292 patients included in the study, the mean lumbar spine T-score was −1.04 ± 1.68, the lumbar spine Z-score was −0.31 ± 1.68, the femoral neck T-score was −1.38 ± 1.39, and the femoral neck Z score was −0.66 ± 1.23. According to the WHO criteria based on lumbar spine T-scores, 19.2% of 292 patients were osteoporotic, 36.3% had osteopenia, and 44.4% had lumbar spine T-scores within the normal range. In the femoral neck area, the prevalence of osteoporosis was slightly higher (26%). The prevalence of osteoporosis was 23.3% in female patients and 16.6% in male patients with no statistically significant difference between the sexes. Agreements of lumbar spine and femoral neck T-scores for the diagnosis of osteoporosis were 66.7% and 27.3% and 83.3% for osteopenia and normal BMD values, respectively. Among the clinical and laboratory parameters we investigated in this study, the body mass index (BMI) (P < 0.001), daily urine output, and urea clearance time × dialysis time/volume (Kt/V) (P < 0.05) were statistically significantly positive and Ca × PO4 had a negative correlation (P < 0.05) with the lumbar spine T scores. Femoral neck T scores were also positively correlated with BMI, daily urine output, and KT/V; and they were negatively correlated with age. Intact parathyroid hormone levels did not correlate with any of the BMD parameters. Femoral neck Z scores were correlated with BMI (P < 0.001), and ionized calcium (P < 0.05) positively and negatively with age, total alkaline phosphatase (P < 0.05), and Ca × P (P < 0.01). The overall prevalence of fractures since the initiation of PD was 10%. Our results indicated that, considering their DEXA-based BMD values, 55% of chronic PD patients have subnormal bone mass—19% within the osteoporotic range and 36% within the osteopenic range. Our findings also indicate that low body weight is the most important risk factor for osteoporosis in chronic PD patients. An insufficient dialysis dose (expressed as KT/V) and older age may also be important risk factors for osteoporosis of PD patients.

Phosphorus control in peritoneal dialysis patients

Hyperphosphatemia is independently associated with an increased risk of death among dialysis patients. In this study, we have assessed the status of phosphate control and its clinical and laboratory associations in a large international group of patients on chronic peritoneal dialysis (PD) treatment. This cross-sectional multicenter study was carried out in 24 centers in three different countries (Canada, Greece, and Turkey) among 530 PD patients (235 women, 295 men) with a mean+/-s.d. age of 55+/-16 years and mean duration of PD of 33+/-25 months. Serum calcium (Ca(2+)), ionized Ca(2+), phosphate, intact parathyroid hormone (iPTH), 25-hydroxy vitamin D(3), 1,25-dihydroxy vitamin D(3), total alkaline phosphatase, and bone alkaline phosphatase concentrations were investigated, along with adequacy parameters such as Kt/V, weekly creatinine clearance, and daily urine output. Mean Kt/V was 2.3+/-0.65, weekly creatinine clearance 78.5+/-76.6 l, and daily urine output 550+/-603 ml day(-1). Fifty-five percent of patients had a urine volume of <400 ml day(-1). Mean serum phosphorus level was 4.9+/-1.3 mg per 100 ml, serum Ca(2+) 9.4+/-1.07 mg per 100 ml, iPTH 267+/-356 pg ml(-1), ionized Ca(2+) 1.08+/-0.32 mg per 100 ml, calcium phosphorus (Ca x P) product 39+/-19 mg(2)dl(-2), 25(OH)D(3) 8.3+/-9.3 ng ml(-1), 1,25(OH)(2)D(3) 9.7+/-6.7 pg ml(-1), total alkaline phosphatase 170+/-178 U l(-1), and bone alkaline phosphatase 71+/-108 U l(-1). While 14% of patients were hypophosphatemic, with a serum phosphorus level lower than 3.5 mg per 100 ml, most patients (307 patients, 58%) had a serum phosphate level between 3.5 and 5.5 mg per 100 ml. Serum phosphorus level was 5.5 mg per 100 ml or greater in 28% (149) of patients. Serum Ca(2+) level was > or =9.5 mg per 100 ml in 250 patients (49%), between 8.5 and 9.5 mg per 100 ml in 214 patients (40%), and lower than 8.5 mg per 100 ml in 66 patients (12%). Ca x P product was >55 mg(2)dl(-2) in 136 patients (26%) and lower than 55 mg(2)dl(-2) in 394 patients (74%). Serum phosphorus levels were positively correlated with serum albumin (P<0.027) and iPTH (P=0.001), and negatively correlated with age (P<0.033). Serum phosphorus was also statistically different (P = 0.013) in the older age group (>65 years) compared to younger patients; mean levels were 5.1+/-1.4 and 4.5+/-1.1 mg per 100 ml, respectively, in the two groups. In our study, among 530 PD patients, accepted uremic-normal limits of serum phosphorus control was achieved in 58%, Ca x P in 73%, serum Ca(2+) in 53%, and iPTH levels in 24% of subjects. Our results show that chronic PD, when combined with dietary measures and use of phosphate binders, is associated with satisfactory serum phosphorus control in the majority of patients.

Is there any relationship between serum levels of interleukin-10 and atherosclerosis in hemodialysis patients?

Objective. Cardiovascular complications due to atherosclerosis (AS) are the major cause of mortality in hemodialysis (HD) patients. Inflammation may play an important role in the development of AS. Several studies have demonstrated an association between AS and acute-phase proteins and cytokines in the general population and in HD patients. Interleukin-10 (IL-10) is an anti-inflammatory cytokine. The aim of this study was to compare serum levels of inflammatory and anti-inflammatory indicators in HD patients according to the presence or absence of AS. Material and methods. A total of 33 HD patients were studied. AS was defined as the presence of plaques as detected by Doppler ultrasonography. The patients were subgrouped according to the presence or absence of plaques. Serum levels of IL-1, -2, -6 and -10, C-reactive protein (CRP) and tumor necrosis factor-α (TNF-α) were measured. Risk factors for AS, such as age, gender, hypertension, hyperlipidemia and duration of HD, were also evaluated. Results. Patients with AS had significantly higher high sensitivity (hs)-CRP and lower IL-10 levels. Blood pressure was also elevated in patients with AS. There was an inverse correlation between CRP and IL-10 levels in patients with AS. Conclusion. Patients with AS undergoing HD had low serum levels of the anti-inflammatory cytokine IL-10 and high serum levels of hs-CRP. These results may suggest that limitation of the anti-inflammatory response in atherosclerotic uremic patients is a triggering or contributory factor for AS.

Which Parameter Is More Influential on the Development of Arteriosclerosis in Hemodialysis Patients

Arteriosclerosis is characterized by stiffening of arteries. The incremental elastic modulus (Einc) measurement is a good marker of arterial wall stiffness. Metabolic, inflammatory and hemodynamic alterations cause structural changes and vascular complications in end stage renal disease. The aim of the present study was to evaluate the factors that may affect the development of arteriosclerosis by measurement of Einc in hemodialysis (HD) patients. Thirty-two patients (16 men; 16 female) on chronic HD with a mean age of 42.2 ± 19.3 (range: 15–80) were included in the study. The carotid Einc was measured to determine arteriosclerosis by high-resolution echo-tracking system (Acuson Aspen, Acuson Corp., Mountain View, California, USA). Einc measurement was calculated from transcutaneous measurements of common carotid arterial (CCA) internal diameter and wall thickness and carotid pulse pressure. Common carotid compliance and distensibility were determined from changes in carotid artery diameter during systole and simultaneously measured carotid pulse pressure. Common carotid artery stuffiness (Einc) was influenced by age, systolic blood pressure (SBP), pulse pressure (PP), calcium (Ca) and alkaline phosphatase (ALP). The distensibility of CCA was correlated with age, SBP, diastolic blood pressure (DBP), PP, Ca, ALP, and parathormone (PTH). The inflammatory parameter, hs-CRP, was increased with Einc. The mean Einc measurement was found significantly increased in patient receiving vitamin D. In conclusion, the stiffening of carotid artery in HD patients is related not only to hemodynamic changes (increased SBP, PP) but also to metabolic (increased Ca) and to inflammation (increased hs-CRP). Carotid Einc is accepted independent risk factor for cardiovascular mortality. Because of the positive correlation between Einc and serum Ca, vitamin D and Ca containing phosphorus (P) binders should be used carefully.

Effect of tempol (4‐hydroxy tempo) on gentamicin‐induced nephrotoxicity in rats

We investigated the effects of tempol (4‐hydroxy tempo), a membrane‐permeable radical scavenger, on gentamicin‐induced renal failure in rats. The rats were given gentamicin (100 mg/kg/day, i.p., once a day); and gentamicin (100 mg/kg/day, i.p.) and tempol (3.5, 7 or 14 mg/kg/day, i.p., once a day). At the end of 7 days, the gentamicin group produced the remarkable nephrotoxicity, characterized by a significantly decreased creatinine clearance and increased serum creatinine, blood urea nitrogen (BUN) and daily urine volume when compared with controls. In control the BUN value was 21.2 ± 0.07 (mg/100 mL); in comparison, it was 96.9 ± 6.03 in gentamicin group (P < 0.05). Renal histopathologic examination confirmed acute tubular necrosis in this group. In rats treated with gentamicin and tempol a partial improvement in biochemical and histologic parameters was observed. BUN values were 96.9 ± 6.03 and 36.3 ± 2.39 in gentamicin, and gentamicin plus tempol (14 mg/kg) treated groups, respectively (P < 0.05). These results suggest that the administration of tempol may have a protective effect on gentamicin‐induced nephrotoxicity in rats.

Heart Rate Variability, Left Ventricular Functions, and Cardiac Autonomic Neuropathy in Patients Undergoing Chronic Hemodialysis

Objective. Autonomic neuropathy and impairment of left ventricular functions (LVF) have been frequently encountered in chronic renal failure (CRF). The aim of the present study was to evaluate the relationship of cardiac autonomic modulation impairments, as assessed by means of heart rate variability (HRV), with clinical characteristics, and left ventricular function in the patients with CRF undergoing hemodialysis (HD). Methods. Twenty control subjects (Group I) and 22 comparable by age and gender patients with CRF undergoing hemodialysis (Group II) were enrolled in the study. After routine clinical and biochemical evaluations, electrocardiography, and 2 Dimensional, M Mode echocardiography were performed in all participants. Frequency domain HRV analysis was studied by using Kardiosis System. The powers (P1 and P2) and the central frequencies (F1 and F2) of low and of high frequency spectral bands were recorded. Results. End systolic (ESV) and end diastolic volumes (EDV) were significantly higher in Group II (59.3 ± 21.1 mL vs. 34.0 ± 14.3 mL and 131.5 ± 37.3 mL vs. 96.9 ± 18.9 mL, p<0.01, p<0.05, respectively) when compared to those of Group I. Ejection fraction (EF) and fractional shortening (FS) were significantly lower in Group II than in control subjects (52.3 ± 2.4% vs. 63.7 ± 10.1% and 0.29 ± 0.01 vs. 0.34 ± 0.07, p<0.001, p<0.05, respectively). P1 and P2 were decreased in Group II than in Group I (136.2 ± 173.9 m s2 vs. 911.0 ± 685.5 and 96.5 ± 149.6 vs. 499.7 ± 679.5, p<0.001, p<0.01, respectively). Significant correlations were found between high frequency spectral power and dialysis duration (DD), ESV, EDV, EF, FS (r = 0.52 p<0.01, r = 0.68 p<0.001, r = 0.65 p<0.002, r = 0.66 p<0.02, and r = 0.69 p<0.01). Conclusion. As a result, the dependence of cardiac autonomic neuropathy on the disease duration and degree of left ventricular function impairment was shown in the patients undergoing chronic hemodialysis.

Lactic acidosis induced by metformin in a chronic hemodialysis patient with diabetes mellitus type 2

Metformin is a biguanide group oral antidiabetic drug used for the treatment of type 2 diabetes mellitus. Nausea, vomiting, diarrhea, abdominal pain, and anorexia are the most common adverse effects encountered during treatment. Lactic acidosis is a serious side effect seen with metformin use, and while the incidence of lactic acidosis is similar to other oral antidiabetics, metformin is not recommended to patients with certain risk factors, such as cardiovascular, pulmonary, and renal and liver failure. We describe a chronic hemodialysis patient treated with metformin, presenting to the nephrology department with altered mental status.

Severe acute renal failure due to tubulointerstitial nephritis, pancreatitis, and hyperthyroidism in a patient during rifampicin therapy

It is well known that rifampicin can cause nephrotoxicity. Rifampicin-related pancreatitis and hyperthyroidism are rarely reported in the same patient in the presence of tubulointerstitial nephritis. Reported herein is the medical management of a patient with hemolytic anemia, acute renal failure, pancreatitis, and hyperthyroidism during with rifampicin therapy. A 50-year-old man was admitted to the hospital owing to abdominal colic and acute renal failure. He was treated with 2 courses of tetracycline-rifampicin for brucellosis 3 weeks and 4 months prior to admission. Physical examination showed blood pressure of 130/70 mm Hg, pulmonary crackles, and edema. Laboratory findings are detailed in the case report. Findings of abdominal ultrasonography suggested edematose pancreatitis and thyroid ultrasonography showed several solid nodules. Renal biopsy showed tubu-lointerstitial nephritis. Although rifampicin-related tubulointerstitial nephritis and acute renal failure are not uncommon during rifampicin therapy, the convergence of hyperthyroidism, pancreatitis, tubulointerstitial nephritis, and acute renal failure rarely presents in the same patient. Although pancreatitis, tubulointerstitial nephritis, and acute renal failure were ameliorated with corticoid therapy within 2 months, hyperthyroidism continued and required antithyroid therapy. In conclusion, rifampicin may trigger hyperthyroidism in patients with goiter.

Oxidative-antioxidative system in peripartum acute renal failure and preeclampsia-eclampsia.

Background: Preeclampsia‐eclampsia and acute renal failure in peripartum women can be the cause of mortality and morbidity. There are many different reports about oxidative–antioxidative systems in preeclampsia‐eclampsia. Until now, products of activated oxidative–antioxidative systems were not evaluated in peripartum women with acute renal failure. In this study, our aim was to evaluate the oxidative–antioxidative systems in peripartum women with acute renal failure and/or preeclampsia‐eclampsia. Methods: The study groups consisted of 17 peripartum women (first week of delivery) with acute renal failure (G I), 11 preeclamptic (G II), 11 healthy pregnancy (≥ 30 weeks of pregnancy) (G III), and 11 healthy women (G IV) aged between 18–38 years. Superoxide dismutase (SOD), glutathione peroxidase (GSHPx) in erythrocytes, and plasma malondialdehyde (MDA) levels were measured in all groups. SOD, GSHPx, and MDA levels were also measured at the onset of acute renal failure (G IA), regression of renal dysfunction (G IB) and recovery of renal functions (G IC). Results: MDA levels were 11.95 ± 4.25, 9.22 ± 3.62, 5.10 ± 3.65, 3.40 ± 1.27, 4.91 ± 2.06, 4.24 ± 1.67 mmol/mL in G IA, G IB, G IC, G II, G III, and G IV, respectively. SOD activity in erythrocyte were 3269.23 ± 1437.83, 2641.35 ± 1411.13, 2056.35 ± 1143.11, 924 ± 160.04, 1057.91 ± 257.03, 861.63 ± 243.28 Ug/Hb in G IA, G IB, G IC, G II, G III, and G IV, respectively. GSHPx activity in erythrocyte was 70.17 ± 23.52, 58.27 ± 23.75, 45.44 ± 17.60, 24.48 ± 6.77, 26.28 ± 7.27, 32.95 ± 8.24 Ug/Hb in G IA, G IB, G IC, G II, G III, and G IV, respectively. MDA levels and activities of SOD, GSHPx in erythrocytes were highest in GIA The values of MDA, SOD, and GSH‐Px in G IA, G IB, and G IC were significantly different from each other and decreased while regaining of renal functions. Preeclampsia‐eclampsia or normal pregnancy did not cause elevation of plasma MDA levels and GSHPx, SOD in erythrocyte. Conclusion: Although SOD and GSHPx in erythrocytes and plasma MDA level were found to be similar in healthy women, pregnant women, and preeclamptic women; SOD, GSHPx, and MDA increased at the beginning and decreased during recovery of renal functions in peripartum women with acute renal failure.

Long-term comparative results of C0 and C2 monitoring of CyA in renal transplanted patients

The purpose of this study was to evaluate the effects of CyA monitoring using Co monitoring (fasting level after 12 h from last dose), and C2 monitoring (2 h after morning dose) on renal functions, lipid levels, CyA levels, and daily dosages of CyA in renal transplanted patients in the posttransplant period from the first month to the 36th month. In our center between 1992–2003, 37 of the 54 renal transplanted patients were treated with CyA, prednisolone, and mycophenolate mofetil or azathioprine. The mean age was 32.36 ± 10.32 and 35.00 ± 10.23 (p = 0.39) in Co (M/F: 18/7) and in C2 (9/3), respectively. Cadaveric donor (d), living related d, and living unrelated d were in four patients (p), 17 p and four p in Co, and two p, seven p, and three p in C2, respectively (p = 0.79). Chronic allograft nephropathy (CAN) developed in 13 p (52%) and one p (8.3%) in Co and in C2, respectively (p = 0.013). Creatinine clearance values were 72.31 ± 23.10 mL/min and 78.73 ± 22.42 mL/min (p:0.621) at first month, 64.97 ± 22.58 mL/min and 78.00 ± 19.90 mL/min (p:0.065) at sixth month, 56.50 ± 19.62 mL/min and 76.62 ± 21.06 mL/min (p:0.006) at 12th month, 50.28 ± 24.79 mL/min and 80.87 ± 18.24 mL/min (p< 0.001) at 24th month, and 55.15 ± 19.21 mL/min and 86.65 ± 14.97 mL/min (p:0.004) at 36th month in C0 and C2, respectively. The mean daily dosages of CyA were 354.35 ± 122.63 and 266.67 ± 64.95 mg/d (p:0.031) at first month, 277.17 ± 77.94 and 250.00 ± 73.31 mg/d (p:0.228) at sixth month, 247.92 ± 58.48 and 211.36 ± 62.61 mg/d (p:0.09) at 12th month, 232.95 ± 56.90 and 170.45 ± 41.56 mg/d (p:0.003) at 24th month, and 240.63 ± 52.34 and 153.57 ± 46.61 mg/d (p:0.002) at 36th month in C0 and C2, respectively. In C2, systolic and diastolic blood pressure, uric acid, total cholesterol (C), LDL-C, and triglyceride levels were lower than those monitored with C0. In C2, HDL-C levels were also higher than those monitored with C0. None of these patients returned to dialysis or died in this period. In conclusion, during the first 36 months with monitoring C2, preservation of renal function, control of blood pressure serum lipids and uric acid were better than those with monitoring C0. In addition, daily dose of CyA was lower in C2 method and, at the same time, this effect of C2 can be accepted as cost effective.