Cetin Ozener

Association between salt sensitivity and target organ damage in essential hypertension

Cardiovascular events occur more frequently in sodium-sensitive patients with essential hypertension; recently, sodium sensitivity was shown to be a cardiovascular risk factor independently of other classic factors such as blood pressure and cigarette smoking This study examined the relationship between salt sensitivity status and target organ damage in hypertensive patients. Ninety-six patients (35 men, 61 women) with moderate essential hypertension were studied for salt sensitivity status and the presence of target organ damage, including hypertensive retinopathy, serum creatinine, creatinine clearance, and urinary albumin excretion (UAE). Four different patterns of left ventricular anatomic adaptation were identified by categorizing patients according to the values of left ventricular mass index and relative wall thickness by the means of echocardiography. Forty-five (47%) patients were shown to be salt-sensitive, in contrast to 51 (53%) salt-resistant subjects. Serum creatinine and UAE were significantly higher in the group of salt-sensitive hypertensives (P < .05 and P < .001, respectively). Left ventricular mass index (LVMI), relative wall thickness (RWT), and left atrial index (LAI) were all significantly higher in the group of salt-sensitive hypertensive patients. Concentric hypertrophy was significantly more prevalent in the salt-sensitive group (37.8% v 11.8%; P < .01). The prevalence of hypertensive retinopathy in the salt-sensitive group was 84.4%, in contrast to 59.6% in the salt-resistant group (P < .01). Multivariate regression analysis revealed salt sensitivity as a significant predictor of LVMI, RWT, and UAE, independently of age, body mass index, and mean blood pressure. In conclusion, salt-sensitive hypertensive patients are more prone to develop severe hypertensive target organ damage that may enhance their risk of renal and cardiovascular morbidity.

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.

Macroprolactin does not contribute to elevated levels of prolactin in patients on renal replacement therapy

Objective  Three molecular forms of PRL with molecular weights of 23, 50–60 and > 100 kDa have been defined. The high‐molecular‐weight forms are called macroprolactin. Different immunoassays produce varyingly elevated results with macroprolactin‐containing sera. The kidneys are reported to clear 25% of PRL from the circulation. Hyperprolactinaemia is seen in 20–75% of patients with chronic renal failure (CRF). PRL clearance rate has been reported to be reduced in CRF and the resulting hyperprolactinaemia is due to reduced renal function.

Colchicine and Secondary Amyloidosis

Excerpt To the Editors:We are writing to support the observations in the letter by Zemer and Langevitz that secondary amyloidosis could be treated with colchicine (1). We have followed a 52-year-ol...

Unusual causes of peritonitis in a peritoneal dialysis patient: Alcaligenes faecalis and Pantoea agglomerans

An 87 -year-old female who was undergoing peritoneal dialysis presented with peritonitis caused by Alcaligenes faecalis and Pantoea agglomerans in consecutive years. With the following report we discuss the importance of these unusual microorganisms in peritoneal dialysis 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.

QT Dispersion in Hemodialysis and CAPD Patients

Prolongation of repolarization dispersion (QT interval dispersion) measured from the 12-lead surface ECG has been associated with sudden cardiac death and ventricular tachyarrhythmias in a variety of cardiac disorders. The aim of our study was to assess the effects of hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) on QT dispersion in end-stage renal disease patients. 20 chronic HD patients (mean age 57.75 ± 13.79 years) and 20 CAPD patients (mean age 50.79 ± 14.94 years) who had no complaints and symptoms of cardiac arrhythmias as well as 20 healthy volunteers (mean age 48.74 ± 10.88 years) underwent ECG testing. All HD patients were on bicarbonate three times weekly with cuprophane capillaries. 12-lead ECGs were recorded on the day after HD. The CAPD patients were on a standard CAPD program (four times daily with 2,000 cm3 peritoneal fluid). ECGs were recorded when the patients were receiving their regular standard CAPD program. All ECGs were analyzed manually by one observer. There were no statistically significant differences in dialysis duration, blood urea nitrogen, creatinine, sodium, calcium, and parathormone values between the HD and CAPD patients. The serum potassium values were significantly higher in HD patients when compared to CAPD patients. There was no difference in the mean of maximal QT among all three groups. The rate of QT interval dispersions was significantly higher in HD and CAPD patients as compared with healthy controls (p < 0.05). There was no statistically significant difference in the QT dispersion rates between HD and CAPD patients. In conclusion, there is a tendency to cardiac arrhythmias in HD patients during the postdialysis period. Although CAPD patients are receiving dialysis daily, they also have higher rates of QT dispersions and accordingly a tendency to arrhythmias.

Renal Protective Effects of Leukotriene Receptor Blockers in an Experimental Model of Cyclosporine Nephrotoxicity

BACKGROUND Chronic cyclosporine (CsA) nephrotoxicity is associated with renal fibrosis and hyaline arteriolopathy. Fibrogenic cytokines, such as transforming growth factor-beta (TGF-beta) and vascular endothelial growth factor (VEGF), play a pivotal role in CsA nephrotoxicity. Previous studies have demonstrated the possible role of leukotrienes (LT) in chronic CsA nephrotoxicity. The aim of this study was to examine the possible beneficial effects of LT blockers in attenuating the morphological and histochemical effects induced by CsA in a rat model of CsA nephrotoxicity. MATERIALS AND METHODS Twenty-four male Wistar rats were divided into 3 groups (n = 8). The first group (G1) was treated with vehicle intraperitoneally (IP) for 60 days. The second group (G2) was treated with 15 mg/kg CsA IP for 60 days. The third group (G3) was treated with the same dose of CsA plus 4 mg/kg montelukast administered by oral gavage for 60 days. RESULTS There was a statistically significant decrease in glomerular filtration rate (GFR) among G2 compared with G1 animals: 0.41 +/- 0.03 vs 1.63 +/- 0.12 mL/min (P < .001), or G3 hosts: 0.41 +/- 0.03 vs 0.95 +/- 0.05 mL/min (P < .005), respectively. The percentage of hyaline arteriolopathic changes was higher in G2 than G1 or G3: 81.66% +/- 8.2% vs 11.83% +/- 0.87% (P < .01) or 37.0% +/- 8.8% (P < .01), respectively. Fibrosis score was higher in G2 compared with G1 or G3: 1.5 +/- 0.04 vs 0.16 +/- 0.02 (P < .001) and 1.0 +/- 0.05 (P < .05), respectively. TGF-beta and VEGF immunoexpression were significantly increased in G2 compared with G1 (P < .05) or G3 (P < .05). CONCLUSIONS Our study suggested that LT may play a critical role in the pathogenesis of chronic CsA nephrotoxicity; the administration of montelukast, a LT receptor blocker, may prevent CsA-induced nephrotoxicity.

Effects of spironolactone in an experimental model of chronic cyclosporine nephrotoxicity.

BACKGROUND Cyclosporine (CsA)-associated nephrotoxicity is a long-term complication in transplant patients. Chronic CsA nephrotoxicity is associated with renal fibrosis and hyaline arteriolopathy. The aim of this study was to investigate the effect of spironolactone on functional and structural alterations as well as on platelet-derived growth factor B (PDGF-B) and transforming growth factor (TGF) beta expression induced by CsA in a rat model of chronic CsA nephrotoxicity. MATERIALS AND METHODS Twenty-four rats were divided into 3 groups. Group 1 (G1) received vehicle only (V); G2, CsA (15 mg/kg/d; CsA) by intraperitoneal (IP) injection; and G3, a similar CsA dosage + spironolactone (20 mg/kg/d; CsA + Ald.) by the oral route. At the end of 28 days, glomerular filtration rate (GFR) and blood CsA levels were measured as well as histopathological and immunohistochemical analyses performed on renal tissue. RESULTS Mean CsA trough levels in G2 and G3 were both above 2000 ng/mL. In G2, GFR was lower than G1 and G3 (0.35 +/- 0.05, 1.64 +/- 0.24, and 1.20 +/- 0.25 mL/min, respectively; P < .001). There was a significantly increased number of arteriolopathic changes in G2 and G3 vs G1 (16% +/- 3.7%, 15% +/- 6.8%, 3% +/- 1.2%, respectively; P < .001). Interstitial fibrosis was significantly increased in G2 vs G1 and G3 (52%, 0%, 27%, respectively; P < .05). Marked by up-regulated PDGF-B and TGF beta expressions were observed in G2 vs G1 or G3: 100%, 0%, 37.5%, respectively, for PDGF-B (P < .001) and 87.5%, 0%, 12.5%, respectively, for TGF beta (P < .001). CONCLUSION Our results suggested that chronic CsA nephrotoxicity may be mitigated by aldosterone receptor blockade which seemed to be associated with down-regulation of PDGF-B and TGF beta expression.

Tetracycline-Induced Acute Interstitial Nephritis as a Cause of Acute Renal Failure

Acute interstitial nephritis with severe acute renal failure is reported following tetracycline treatment in a 22-year-old male medical student. Acute renal failure developed within 48 h of a single repeated tetracycline dose and presented 2 days after taking the drug when there was oliguria, nausea, vomiting and bilateral loin pain without rash and fever. The serum creatinine concentration was 8.6 mg/dl and blood urea nitrogen 84 mg/dl. Examination of the urinary sediment revealed 15–20 RBCs per high-power field, and occasional granular and hyaline casts. Percutaneous renal biopsy performed immediately after admission revealed acute interstitial nephritis with immune complexes along the tubular basement membrane and intact glomeruli and was consistent with type 2 interstitial nephritis. Within 4 days of commencement of steroid treatment and hemodialysis, the urine output started to increase with improvement in serum creatinine and BUN levels and after 2 weeks of therapy hemodialysis was discontinued. He remains well 1 year following his illness with complete normalization of his renal function. Although a number of renal side effects of tetracycline antibiotics have been reported, acute interstitial nephritis is rarely caused by tetracycline treatment having been reported just twice following systemic use of minocycline.