Does Renal Tubular Injury-Induced Local Tissue Hypoxia Involve Post-Transplantation Erythrocytosis?

BACKGROUND: The pathogenesis of post-transplantation erythrocytosis (PTE) is not well understood and appears to be multifactorial. Our hypothesis in this study was that several factors, including toxicity of calcineurin inhibitor, immunologic factors, and chronic allograft nephropathy, can trigger local tissue hypoxia in peritubular interstitium, which is where production of erythropoietin (EPO) takes place. This local interstitial tissue hypoxia can cause an increase in renal EPO production, which induces the development of PTE. METHODS: This cross-sectional study included 15 renal transplant recipients, in whom polycythemia developed after kidney transplantation, with elevated hematocrit level to >51%. Forty-eight age- and gender-matched renal transplant recipients with normal hematocrit level were included as the renal transplant control group. In addition, 13 age- and gender-matched healthy subjects were also included as the healthy control group. We used urine hypoxia-inducible factor-2 alpha (HIF-2α) levels to evaluate whether there is local tissue hypoxia in renal allograft. HIF-2α levels were measured by double antibody sandwich enzyme-linked immunosorbent assay (ELISA). Serum EPO and insulin-like growth factor-1 (IGF-1) levels were also measured. RESULTS: HIF-2α levels were significantly lower in the polycythemia group than the other two groups, but there was no significant difference between the healthy control group and the renal transplant control group with regard to HIF-2α levels. There was no significant difference among the 3 study groups in terms of levels of serum EPO and IGF-1. CONCLUSION: Local tissue hypoxia in renal allograft does not seem to play an important role in the development of PTE.

Association Between Cardiac Valvular Calcification and Serum Fetuin-A Levels in Renal Transplant Recipients.

BACKGROUND: The presence of cardiac valvular calcification in patients with chronic kidney disease has become important. We aimed to evaluate the prevalence of cardiac valvular calcification and its association with serum Fetuin-A levels in kidney transplant recipients. METHODS: The cardiac valvular calcification was assessed by echocardiography in 89 kidney transplant recipients. Serum Fetuin-A levels were measured by use of the enzyme-linked immunosorbent assay method. RESULTS: Patients were divided into 3 groups: patients without cardiac valvular calcification (n = 14), patients with aortic valve calcification (n = 51), and patients with both aortic and mitral valve calcification (n = 24). Aortic calcification area and number of aortic calcifications were significantly increased in the group with aortic and mitral calcification group compared with the other two groups. These two parameters were also significantly increased in patients with cardiac valvular calcification compared with patients without cardiac valvular calcification. Serum Fetuin-A levels were significantly increased in patients with aortic valve calcification compared with the other two groups, whereas there were no significant differences between these two groups. Serum Fetuin-A levels were positively correlated with blood urea nitrogen level (r = .241, P = .025) and serum creatinine level (r = .262, P = .014), whereas it was negatively correlated with serum phosphorus level (r = -.409, P < .001). CONCLUSIONS: Serum Fetuin-A levels can be taken into consideration for the assessment of patients in terms of cardiac valvular calcification, depending on the relationship between serum Fetuin-A levels and cardiac valvular calcification during follow-up after kidney transplantation.

Relationships Between Metabolic Syndrome, Microalbuminuria, and C-Reactive Protein in Turkish Kidney Transplant Recipients.

AIM: The aims of this study were to report the prevalence of metabolic syndrome (MS) in a cohort of Turkish kidney transplant recipients and to define the relationships between MS, microalbuminuria and C-reactive protein (CRP), which are cardiovascular risk factors, in kidney transplant setting. METHODS: This cross sectional study included 170 adult renal transplantation recipients with a mean follow-up of 53.1 ± 49.9 months. The diagnosis of MS was made according to the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III) criteria. Microalbuminuria was defined as a urinary albumin/creatinine ratio of 30-300 mg/g. CRP levels ≥6.0 were classified as high CRP. RESULTS: Mean age was 39.3 ± 11 years. The prevalence of MS was 45.8% (n = 78). The prevalence of microalbuminuria was not different in patients with MS compared to those without MS (39.7% vs 37%, P = .428). In multivariate logistic regression analyses, systolic blood pressure (SBP) (odds ratio 1.68; 95% confidence interval [CI] 1.12-2.52; P = .011) and high fasting glucose (odds ratio 2.82; 95% confidence interval [CI] 1.16-6.86; P = .022) were significantly associated with microalbuminuria. When patients with MS and high CRP were compared with patients with normal CRP and without MS, microalbuminuria did not differ between the groups (P = .213). CONCLUSION: The prevalence of MS in our kidney recipient cohort was found to be increased compared to general population. MS was not related to increased prevalence of microalbuminuria, even when combined with high CRP. Microalbuminuria was associated with elevated SBP and hyperglycemic status.

Microalbuminuria is associated with high prevalence of anemia in renal transplant recipients.

BACKGROUND AND AIM: Prevalence of anemia is higher in diabetic patients with microalbuminuria than those with normoalbuminuria despite the absence of significant renal impairment. The aim of this study was to investigate whether there was a relationship between microalbuminuria and anemia in renal transplant recipients (RTRs). PATIENTS AND METHOD: Twenty-eight RTRs with microalbuminuria and 21 control RTRs with normoalbuminuria were classified based on urinary albumin creatinine ratios (UACR) of 0.03-0.3 versus <0.03, respectively. Anemia was defined as a hemoglobin level <13 g/dL for men and <12 g/dL for women. RESULTS: Anemia was observed in 13 (46.4%) microalbuminuric and 4 (19%) normoalbuminuric patients (P = 0.044). Hemoglobin level was significantly lower in the microalbuminuric than the normoalbuminuric group (13.3 ± 1.3 g/dL vs 14.4 ± 1.9 g/dL, respectively; P = .018). Although creatinine clearance was significantly higher among the normoalbuminuric group (84 ± 30 mL/min vs 65 ± 22 mL/min, respectively; P = .017), mean creatinine clearance in microalbuminuric group was >60 mL/min, the threshold value for anemia due to erythropoietin (EPO) deficiency. In contrast, there was no significant difference between the 2 groups for age, gender, donor source, and transplant duration. CONCLUSION: Anemia was frequent among RTRs displaying microalbuminuria, which may reflect EPO deficiency due to the tubulointerstitial injury of chronic allograft nephropathy. The EPO deficiency may begin before significant deterioration in excretory function of the kidney.

Loss of bone mineral density in renal transplantation recipients.

AIM: This study investigated the prevalence and contributing factors of loss of bone mineral density after renal transplantation among Turkish patients. PATIENTS AND METHODS: The study included 70 subjects, namely 50 males and 20 females of overall mean age of 36.94 ± 10.09 years. We measured femoral neck mineral density by dual-energy X-ray absorptiometry (DEXA). A T score above -1 was defined as a normal bone mineral density compared with T scores of -1.0 to -2.5 or below -2.5 which were defined as either osteopenia or osteoporosis, respectively. RESULTS: At a median duration of 23 months after renal transplantation, osteopenia or osteoporosis was observed among 30 (42.9%) or 30 (42.9%) of the 70 patients, respectively. The mean body mass index (BMI) value was significantly higher among the normal than the osteoporotic group: 27.59 ± 4.66 kg/m(2) vs 24.18 ± 3.57 kg/m(2), respectively. However, no significant differences occurred in terms of BMI among the other groups. The amount of proteinuria was significantly lower in the normal than the osteopenic or osteoporotic group: (12.5 (range, 10.0-20.0); 105.0 (10.0-2800.0) or 215.5 (10.0-1880.0) mg/d (P = .001 and .004, respectively). In contrast, there was no significant difference between the amounts of proteinuria displayed by the osteopenic group and the osteoporotic group (P < .05)]. These patient groups showed no difference in age, gender, donor source, cause of end-stage renal disease (ESRD), pretransplant dialysis modality, duration of dialysis, use of a vitamin D preparation, immunosuppressive regimen, posttransplantation period, levels of iPTH or 25 hydroxy vitamin D3 (25OH vit D), exposure to tacrolimus or cyclosporine (CyA), calcium × phosphate product, serum albumin and hemoglobin content, creatinine clearance, or serum bicarbonate concentrations (P > .05). The T scores of the femoral neck correlated with BMI (r: 0.415; P = .001), 25OH vit D level (r: 0.268, P = .026), creatinine clearance (r: 0.273, P = .022), and serum glucose level (r: 0.349, P = .003). It inversely correlated with the amount of proteinuria (r: -0.263, P = .028), serum alkaline phosphatase level (r: -0.329, P = .005), and serum magnesium concentration (r: -0.252, P = .035). Upon multivariate analysis, BMI and 25OH vit D level were observed to be independent risk factors for loss of femoral mineral density. CONCLUSION: Loss of bone mineral density is a common complication that correlates with low BMI values and decreased 25OH vit D levels as major risk factors for this problem.

An underappreciated problem in renal transplant recipients: anemia.

PURPOSE: Posttransplant anemia (PTA) is associated with a higher risk of cardiac mortality, which is the most frequent cause of death among renal transplant recipients. In this study, we sought to determine the prevalence and causes of PTA among Turkish patients. PATIENTS AND METHODS: The study included 75 (52 male, 23 female) adults. Anemia was defined as an hemoglobin (Hb) level < or = 13 g/dL for men and < or = 12 g/dL for women. RESULTS: The prevalence of PTA was 49.3% at a mean duration of 60.45 months after renal transplantation. The most frequent causes of PTA were erythropoietin (EPO) and iron deficiency. The mean Hb level of 12.76 +/- 2.31 g/dL was significantly higher in male compared to female patients (13.26 +/- 2.31 g/dL vs 11.64 +/- 1.93 g/dL, P = .005). The Hb value was positively correlated with creatinine clearance and serum albumin level, and negatively correlated with serum creatinine level, the amount of proteinuria, and cyclosporine level. Creatinine clearance and serum albumin level were found to be an independent risk factors for PTA upon multivariate analysis. Only 12 of 37 anemic patients received treatment for anemia: 5 (13.5%) with EPO and 7 (18.9%) with iron preparations. CONCLUSION: PTA a common complication was unfortunately neglected in this setting. Impaired renal allograft function and decreased serum albumin were major risk factors for PTA. Increased cyclosporine levels were also correlated with decreased Hb concentrations.

The prevalence of carotid artery calcification on the panoramic radiographs of end-stage renal disease patients with peritoneal dialysis: do incidental findings provide life-saving information?

This study investigated the presence of carotid artery calcifications (CACs) on panoramic radiographs (PRs) in end-stage renal disease (ESRD) patients treated with peritoneal dialysis (PD), and analysed the relationship between CAC prevalence and PD duration. A random sample of 110 PRs were collected from ESRD patients (15 with questionable CACs were subsequently excluded). CACs were found in 26 (27.4%) patients; 10 males (23.3% of all males) and 16 females (30.8% of all females). The overall mean PD period was 4.0 +/- 3.2 years. There was a significant difference in PD period between patients with and without CACs (5.3 +/- 3.1 years versus 3.5 +/- 3.1 years, respectively). To our knowledge, this study has the highest CAC prevalence, is the first to be carried out in ESRD patients being treated with PD and has the largest sample of ESRD patients (n = 95). We believe dentists should carefully evaluate patients' PRs for evidence of CACs, enabling these incidental findings to provide life-saving information.

Effect of cyclosporine A on total homocysteine level in a rabbit model.

BACKGROUND: Moderate hyperhomocysteinemia is an independent risk factor for cardiovascular disease. Cyclosporine (CsA) has been suggested to interfere with folate-assisted remethylation of homocysteine, thus causing hyperhomocysteinemia. But, this issue is controversial. In this experimental study, we attempted to determine the association between CsA administration and total homocysteine levels. Working with rabbits that have normal creatinine levels, we obviated the misleading effects of renal functional variations, which are the most important confounding factors affecting total homocysteine level. METHODS: Male New Zealand rabbits fed a standard quantity of diet received 10 days of subcutaneous injections of 10 mg/kg per day CsA. After these loading doses, CsA (20 mg/kg) was administered subcutaneously three times a week for 20 days. After first 30 days, the rabbits were followed for another 30 days without CsA therapy. Plasma creatinine, BUN, and total homocysteine levels were measured on days 0, 10, 30, and 60. RESULTS: There were no significant changes in BUN results on days 0, 10, 30, and 60 (P > .05). There was a slight, but significant, increase in mean creatinine levels during CsA administration (P < .01). However, the mean creatinine levels remained in the normal ranges during the 60 days of study. No significant changes were observed in total homocysteine levels (P > .05) compared to baseline, 10-, 30-, and 60-day values. CONCLUSION: Our experimental research minimized confounding factors. It showed that CsA does not increase total homocysteine levels, confirming clinical studies that reported no association between CsA and total homocysteine.

Obstructive icterus directly related to visceral artery aneurysm in a CAPD patient.

Visceral artery aneurysms (VAA) are uncommon pathologies. We report a case of the first CAPD patient with obstructive jaundice directly related to VAA. A 25-year-old man with a four-year history of hemodialysis followed by two years of CAPD was admitted due to jaundice. He had two episodes of peritonitis. An abdominal ultrasonogram and a selective common hepatic arteriogram confirmed the presence of a 5 cm saccular aneurysm supplied from the gastroduodenal artery and a 4 cm fusiform aneurysm supplied from the proximal part of the common hepatic artery. The gastroduodenal artery was responsible for the impression of the common bile duct. In the operation, the gastroduodenal artery aneurysm was completely excised after its proximal and distal ends were ligated. The proximal and distal ends of the hepatic artery were also ligated. A prosthetic graft (PTFE), which extended from the splenic artery to the distal portion of the hepatic artery, was placed. In this way, the arterial blood flow of the liver was re-established. Patients with VAAs present with a constellation of symptoms including abdominal pain, jaundice and shock (due to rupture of aneurysm). Pancreatitis, and atherosclerosis have been reported to be the most common causes of VAAs. In conclusion, when CAPD patients present with jaundice or hemorrhagic shock with abdominal pain, VAA should be considered in differential diagnosis, especially if patients have a history of frequent pancreatitis episodes, and severe risk factors for atherosclerosis.

Effects of azithromycin on cyclosporine-induced gingival hyperplasia in renal transplant patients.

BACKGROUND: Gingival hyperplasia is a well-known complication of cyclosporine therapy, affecting 21% to 35% of renal transplant patients. Metronidazole, clarithromycin, and azithromycin, all azalid antimicrobial agents derived from the macrolide antibiotic erythromycin, have been used for treatment. Marked improvements in gingival hyperplasia have been recorded in particular with azithromycin. The aim of the present study was to investigate histopathological features of cyclosporine-induced gingival hyperplasia and to evaluate the quantitative efficacy of short-term azithromycin therapy. METHODS: Eighteen renal transplant patients with cyclosporine-induced gingival hyperplasia were included in the study. All patients received azithromycin with a dose of 500 mg/d for 3 consecutive days. Changes in gingival hyperplasia were evaluated by measuring the gingival sulcus depth to the cementum-enamel junction of every tooth in each of the four quadrants on days 0, 7, 30, 90, 180. Gum biopsies were obtained on days 0 and 30; the degree of inflammation was classified as "mild," "intermediate," and "severe". RESULTS: Gingival hyperplasia was reduced in all treated patients throughout the study. The degree of improvement was more significant between 0 to 7 and 7 to 30 days than at other times (respectively, P < .0001 and P < .002). Histopathologically, eight patients had severe and one patient moderate chronic inflammation at the beginning of therapy. Three other biopsies were reported as papilloma, mucosal hyperplasia, and normal gingival tissue biopsy. CONCLUSIONS: Azithromycin appears to be useful to treat cyclosporine-induced gingival hyperplasia in renal transplant patients. Treatment is inexpensive and free from known adverse effects.

Relationship between different body size indicators and hernia development in CAPD patients.

AIMS: A small body size may increase the risk for hernia development in patients on continuous ambulatory peritoneal dialysis (CAPD). The present study investigates whether there is a relationship between body size and hernia development in CAPD patients. MATERIAL AND METHODS: The records of 78 patients on CAPD were reviewed retrospectively. Body mass index (BMI), body surface area (BSA) and total body water (TBW) were calculated in all patients. Correlations between different body size indicators (BMI, BSA and TBW) and hernia development were assessed using analysis of covariance in which we adjusted for sex. RESULTS: A total of 14 patients (17.9%) with no physical evidence of hernia before catheter insertion developed hernias. Body size was significantly lower in CAPD patients with hernias than those without hernias when adjusted for sex. CONCLUSIONS: We conclude that patients with small body size tend to have an increased risk for hernia development. A simple estimation of patients' height, weight, body surface area and total body water would be helpful to predict development of hernias or other complications related to increased intraperitoneal pressure in CAPD patients.

Case report. Successfully treated subcutaneous infection with Sporothrix schenckii in Turkey.

Sporotrichosis is rare in Turkey. We report a 48-year-old man who had subcutaneous sporotrichosis caused by Sporothrix schenckii that was successfully treated with short-term itraconazole and potassium iodide. The isolate was susceptible to itraconazole also in vitro. Short-term itraconazole and potassium iodide should be agents of choice for treatment of subcutaneous sporotrichosis. However, treatment is controversial both in choice of agent used and in duration of therapy.