Urinary angiotensinogen, related factors and clinical implications in normotensive autosomal dominant polycystic kidney disease patients.

BACKGROUND: Although several lines of evidence suggest that renin angiotensin system (RAS) proteins are synthesized by cyst epithelium and dilated tubules, role of intrarenal RAS in the progression of otozomal dominant polycystic kidney disease (ADPKD) is not well known. We aimed to study the levels and clinical correlations of urinary angiotensinogen (UAGT) in normotensive ADPKD patients compared with age- and sex-matched healthy subjects. METHODS: The study included 20 normotensive ADPKD patients (F/M: 11/9) and 20 age and sex matched healthy controls (F/M: 9/11). Diagnosis of ADPKD was made based on Ravine criteria. Twenty-four hours ambulatory blood pressure monitoring (ABPM) was performed. Serum concentrations of creatinine, Na, K, uric acid, and urinary concentrations of Na, K, uric acid, creatinine, protein and albumin were measured. UAGT were measured via commercially available ELISA kit. RESULTS: ADPKD patients had higher urinary albumin:creatinine ratio (UAIb/UCrea) than healthy controls (p < 0.01). UAGT/UCrea levels significantly positively correlated with urinary protein: creatinine ratio (UPro/UCrea) (r = 0.785, p = 0.01), and UAIb/UCrea (r = 0.681, p = 0.01) in normotensive ADPKD patients. CONCLUSION: This pilot study demonstrates that UAGT levels tend to be elevated and are correlated with proteinuria and albuminuria in normotensive ADPKD patients during relatively early stages of the disease.

Changes in oxidative stress in renal graft patients receiving calcineurin inhibitors: cyclosporine versus tacrolimus.

OBJECTIVES: The effects of calcineurin inhibitors on oxidative stress after renal transplant are obscure. This study sought to investigate the changes in plasma oxidative stress and lipid levels in patients receiving cyclosporine or tacrolimus before and after renal transplant for 6 months. MATERIALS AND METHODS: Twenty-one patients and 15 healthy controls were involved in our study. Twelve of the patients were treated with cyclosporine and 9 were treated with tacrolimus. Plasma malondialdehyde, nitrite/nitrate, vitamin C, vitamin E, and plasma glutathione levels, as well as total cholesterol and triglyceride levels, were evaluated before and after transplant for 6 months. RESULTS: Before the transplant, patients had higher malondialdehyde and plasma glutathione levels than did healthy controls (3.76 ± 0.79 nmol/mL vs 3.21 ± 0.57 nmol/mL; P < .05, and 66.6 ± 23.2 µmol/L vs 43.3 ± 26.9 µmol/L; P < .05). In the overall group of patients, a significant increase in malondialdehyde levels was detected 3 and 6 months after transplant (3.76 ± 0.79 nmol/mL vs 4.38 ± 0.87 nmol/mL in the third month; P = .02; and 3.76 ± 0.79 nmol/mL vs 4.28 ± 0.69 nmol/mL in the sixth month; P = .04). A significant reduction in plasma glutathione levels 1 month after transplant and nitrite/nitrate levels 6 months after transplant was found. No changes in vitamin C and vitamin E levels were detected before and after transplant. After 3 and 6 months of transplant, cyclosporine-treated patients had higher levels of total cholesterol and triglycerides when compared with tacrolimus-treated patients. CONCLUSIONS: An enhancement in plasma malondialdehyde levels was found after transplant at 6-month follow-up. However, no significant change in vitamin C, vitamin E, nitrite/nitrate levels between patients and controls was recorded. Although both calcineurin inhibitors showed similar effects on oxidative stress, cyclosporine-treated patients had higher levels of total cholesterol and triglycerides.

Pathologist's puzzle: Membranoproliferative glomerulonephritis-like features in cryoglobulinemic glomerulonephritis.

Mixed cryoglobulinemia is commonly related to chronic HCV infection, and renal complications occur frequently. Typical renal involvement presents with diffuse proliferative glomerular pathology, similar to membranoproliferative glomerulonephritis, with necrotizing arteritis of medium-sized vessels, referred to as cryoglobulinemic glomerulonephritis. However, the histological appearance may vary according to the clinical presentation and treatment applied. Not only membranoproliferative glomerulonephritis but also certain types of systemic vasculitis (Systemic Lupus Erythematosus, Polyarteritis Nodosa), thrombotic microangiopathy, and Waldenstrom's Macroglobulinemia may exhibit similar histopathological findings in the biopsy with cryoglobulinemic glomerulonephritis. For an optimal differential diagnosis, clinicopathological correlation and serological findings should accompany the pathological findings. We present a case of cryoglobulinemic glomerulonephritis, and discuss the differential diagnosis in detail.

Endothelial nitric oxide synthase gene intron 4 polymorphism predicts new onset diabetes mellitus after transplantation in kidney allograft recipients treated with cyclosporin A.

BACKGROUND: Nitric oxide (NO), synthesized from LS: -arginine by the enzyme endothelial nitric oxide synthase (eNOS), is a potent vasodilator and has been implicated in mediating insulin-induced uptake and metabolism of glucose in skeletal muscle. Polymorphisms of the eNOS gene have been associated with altered eNOS activity and NO levels. Although several factors have been demonstrated for new onset diabetes mellitus after transplantation (NODAT), determining a genetic susceptibility for all patients requires further study. In our study, we evaluated the relationship between eNOS gene intron 4 polymorphism and NODAT in kidney allograft recipients. METHODS: A total of 82 consecutive patients who received their first kidney transplantation and maintained graft function for at least a 12-month post-transplant period and who used triple therapy including cyclosporin A (CsA) for maintenance immunosuppression were included. PCR-RFLP was used for genetic analyses. RESULTS: Nine of 82 patients (11%) developed NODAT. Concerning the prevalence of eNOS intron 4 gene polymorphism, a significantly higher percentage of 4a allele carriers developed NODAT than non-carriers [6/26 (23.1%) versus 3/56 (5.4%), P = 0.02]. Compared with non-diabetics, NODAT patients were older (P = 0.04), had higher rate of hepatitis C (P < 0.05) and higher body mass index at the time of transplantation (P = 0.03). In regression analyses, having a 4a allele of the eNOS gene intron 4 polymorphism (P = 0.02) and HCV seropositivity (P = 0.03) were found to be independent risk factors for the development of NODAT. CONCLUSIONS: These findings suggest that carrying a 4a allele of the eNOS gene intron 4 polymorphism is associated with NODAT. This may help us to further understand the individual risk for development of NODAT in kidney allograft recipients under CsA treatment.

The relationship between hypertension and salt intake in Turkish population: SALTURK study.

This population-based epidemiological study was aimed to evaluate the daily salt intake and its relation to blood pressure in a representative group of Turkish population. The enrolled normotensive and hypertensive individuals (n = 1970) completed a questionnaire including demographics, dietary habits, hypertension awareness and drug usage. Blood pressure was measured and to estimate salt consumption, 24-h urine samples were collected. The daily urinary sodium excretion was 308.3 ± 143.1 mmol/day, equal to a salt intake of 18.01 g/day. Salt intake was higher in obese participants, rural residents, participants with lower education levels and elderly. A positive linear correlation between salt intake and systolic and diastolic blood pressures was demonstrated (r = 0.450, p = 0.020; r = 0.406, p = 0.041; respectively), and each 100 mmol/day of salt intake resulted in 5.8 and 3.8 mmHg increase in systolic and diastolic blood pressures, respectively. Salt intake and systolic blood pressure was significantly correlated in normal weight individuals (r = 0.257, p < 0.01). The Turkish population consumes a great amount of salt; salt intake and blood pressure was positively correlated. Efforts in sodium restriction are therefore crucial in the management of hypertension as part of national and global health policies.

Soluble endothelial cell protein C receptor and thrombomodulin levels after renal transplantation.

BACKGROUND: Both thrombomodulin (TM) and endothelial protein C receptor (EPCR) are candidate biomarkers of endothelial damage and have a role of anti-thrombotic defense mechanism in vascular structure. In this study, we aimed to investigate soluble EPCR (sEPCR), soluble TM (sTM) and tumor necrosis factor-alpha (TNF-alpha) levels in hemodialysis (HD) and renal transplant (RTx) recipients. METHODS: Twenty-seven RTx recipients and 15 HD patients were recruited to the study. RTx recipients were evaluated before and 3 months after transplantation. Plasma sEPCR, sTM and TNF-alpha levels were measured at baseline and 3 months later in both groups. Moreover, 27 healthy subjects were evaluated regarding sEPCR. RESULTS: At baseline, there was no difference in sTM, sEPCR, TNF-alpha and C-reactive protein (CRP) between the groups. In paired analysis, sEPCR (266 ± 132 to 117 ± 72 ng/ml), sTM (635 ± 165 to 100 ± 41 ng/ml) and TNF-alpha (11.2 ± 4.3 to 6.0 ± 3.5 pg/ml) were significantly decreased in RTx patients (P < 0.0001) at 3 months, while there was no change in the HD group. In the healthy subjects, sEPCR was found to be 79 ± 26 ng/ml at baseline, which was lower than in both groups. CONCLUSIONS: We showed that the recently proposed endothelial damage biomarkers, sTM and sEPCR, are elevated in HD patients and significantly decrease after kidney transplantation.

Hypertension incidence in Turkey (HinT): a population-based study.

OBJECTIVE: Hypertension incidence is an important determinant of hypertension prevalence and progression. Few studies have been published on hypertension incidence in developing countries despite the high prevalence observed. The aim of this study was to investigate the incidence of hypertension in Turkey. METHODS: The study was designed as an epidemiological cohort study which included the population of the Prevalence, awareness, treatment and control of hypertension in Turkey (PatenT) Study which had 4910 volunteers. Blood pressure measurements were performed three times and a questionnaire was used to obtain data on the present status of hypertension with regards to distributions and alterations of risk factors. RESULTS: In the present study, 4008 (81.6%) participants of the PatenT Study population were contacted after 4 years. After excluding 173 dead and 67 pregnant individuals, the study cohort comprised of 3768 individuals. The overall 4-year incidence rate of hypertension was 21.4%; it reached a maximum of 43.3% in individuals over 65 years of age. Age, initial blood pressure category, and body mass index were the best predictors of the hypertension incidence rate. Multivariate logistic regression analysis revealed that age, obesity, alcohol consumption, and living in rural areas were significant predictors of hypertension. CONCLUSION: Follow-up periods scheduled considering age, initial blood pressure category, and body mass index are important for the early determination of hypertension. As there are limited data regarding hypertension incidence in developing countries, the results of data collected in this study might serve as a model.

Fatal outcome of disseminated invasive aspergillosis in kidney allograft recipients.

Fungal infections in solid organ transplant recipients are of concern due to the related high mortality and morbidity. Aspergillus species are one of the major opportunistic fungal pathogens causing invasive pulmonary infections which rarely involve extrapulmonary organs. The occurrence varies by type of transplantation, with aspergillosis more frequently associated with heart, liver and lung transplantation cases than those involving kidney recipients. Several risk factors have been proposed, with cases occurring early and late after the transplantation. Although pulmonary involvement is the main presentation, invasive extrapulmonary aspergillosis can on rare occasions be observed and is associated with poor prognosis. Herein, we report two cases that presented with extrapulmonary invasive aspergillosis, i.e., one presented with cerebral abscess and the second with soft tissue abscess in the right posterior thigh. While the cerebral abscess was not surgically treated, the soft tissue abscess was surgically drained. When the primary focus was investigated, pulmonary nodulars were found in both cases. Both patients were treated with long-term amphotericin B; however, one patient was lost with functioning graft and the kidney of the second patient failed due to decreased immunosuppression and he died while on maintenance hemodialysis. Invasive extrapulmonary presentation of aspergillosis rarely occurs in kidney transplant recipients and is associated with a high mortality rate.

Comparative effects of renal transplantation and maintenance dialysis on arterial stiffness and left ventricular mass index.

BACKGROUND: Arterial stiffness and left ventricular hypertrophy (LVH) are major independent risk factors for cardiovascular disease in healthy and renal population. In this study, we aimed to investigate comparative long-term effects of renal transplantation (RTx) and of hemodialysis (HD) on both arterial stiffness and LVH. METHODS: Twenty-eight RTx patients, 23 HD patients, and 20 healthy subjects were included in this prospective study. In addition to demographical and laboratory parameters, arterial stiffness [pulse wave velocity (PWV)] and left ventricular mass index (LVMi) were assessed before and one-yr after RTx, and at the baseline and one-yr later in HD patients. RESULTS: There were no differences in the parameters between HD and RTx patients at baseline. PWV was significantly higher than that of healthy controls. After one yr, PWV had significantly decreased in RTx patients, but was unchanged in HD patients. Changes in PWV were significant when both groups were compared (p < 0.0001). Although LVMi significantly decreased after RTx (p = 0.02), changes were not significant between the groups. CONCLUSIONS: Renal transplantation markedly improved arterial stiffness, while it remained elevated in HD patients at the one-yr follow-up. There was no difference between maintenance HD and RTx groups with respect to impact on LVMi in the one-yr follow-up.

Renal tubular acidosis after kidney transplantation--incidence, risk factors and clinical implications.

BACKGROUND: Renal tubular acidosis (RTA) is a non-anion gap metabolic acidosis and is generally mild and asymptomatic in kidney recipients. Although calcineurin inhibitors, suboptimal allograft function, donor age and acute rejection have been associated with RTA, no detailed study has been conducted to investigate the prevalence and clinical implications of RTA in long-term kidney recipients. METHODS: In this cross-sectional study, we enrolled 109 patients (74 males, 35 females) for the study [patients with glomerular filtration rate (GFR) <30 ml/min/1.73 m(2), unstable allograft function, diarrhoea, and respiratory disease were excluded]. Thirty-six patients (33%) were found to have RTA on the basis of plasma bicarbonate, arterial pH, urine and serum anion gap measurements. RESULTS: Deceased donor transplantation [P = 0.034, 95% confidence interval (CI): 1.10-13.27], female gender (P = 0.017, 95% CI: 1.23-8.50), and lower GFR (55.8 +/- 19.4 in RTA and 66.1 +/- 15.9 ml/min/1.73 m(2) in non-RTA, P = 0.002, 95% CI: 1.10-13.27) were independent risk factors for RTA. Also, C-reactive protein was found to be higher in the RTA group (2.7 +/- 1.5 vs 2.0 +/- 1.5 mg/dl, P = 0.03), while no difference was noticed in body mass index or serum albumin. Analysis of the prevalence of osteoporosis and osteopenia in patients with RTA and without RTA, respectively, revealed no difference in frequency of osteoporosis (33% vs 31%) or osteopenia (33% vs 47%). CONCLUSION: Although long-term kidney recipients have a relatively high prevalence of RTA, it is usually mild and subclinical. Further studies are needed to clarify long-term effects of RTA in kidney recipients.

Thrombophilia and avascular necrosis of femoral head in kidney allograft recipients.

BACKGROUND: Thrombophilia has been implicated in the development of avascular necrosis (AVN) in various diseases. We aimed to search for the relation of both prothrombin gene G20210A mutation and factor V G1691A (factor V Leiden) mutation with AVN among kidney transplant recipients. METHODS: Nineteen patients with AVN and 38 control patients without AVN were included. Clinical information was collected, and gender, age, type of renal allograft, duration and type of dialysis, presence of acute rejection, and cumulative doses of ciclosporin and corticosteroid administration were taken into consideration. Genotypes of factor V G1691A and prothrombin G20210A were determined by direct sequencing of genomic DNA. RESULTS: Factor V Leiden mutation was detected in six patients (31.6%) among patients with AVN and in only three patients (7.9%) in the control group (P = 0.048). Two patients (10.5%) in the AVN group were determined to have prothrombin G20210A mutation, while no prothrombin G20210A mutation was detected in the control group. When both of the mutations causing thrombophilia were considered, a total of eight patients (42.1%) in the AVN group and three patients (7.9%) in the control group were identified (P = 0.004). CONCLUSION: Thrombophilia seems to be an important risk factor for development of AVN. More studies are needed to clarify the role of factor V G1691A and prothrombin G20210A mutation for AVN.

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.

Two sisters with familial Mediterranean fever: lack of correlation between genotype and phenotype?

Familial Mediterranean fever (FMF) is an autosomal recessive disorder characterized by attacks of fever and serositis. The most important complication of FMF is renal amyloidosis, which determines the prognosis. The gene coding the disease (MEFV) is identified on the 16th chromosome. The most common MEFV mutations are M694V, M680I, V726A and M694I located on exon 10 and E148Q located on exon 2. Unfortunately, genotype-phenotype correlation is not well established and there are unexplained ethnic differences in amyloidosis rates. We report two sisters with a common genotype (M694V/M694V) presenting with different phenotypic characteristics: one complaining of intermittent abdominal pain, arthritis and fever, while the other was suffering from intermittent pleuritis and fever during attacks. The observation of different phenotypic presentations with a common genotype in two family members shows that different phenotypes cannot be explained by particular mutations. To understand the correlation between genotypic and phenotypic FMF variants the existence of complex alleles, modifier loci, genetic heterogeneity and possible epigenetic factors should be studied extensively.

Tamoxifen in the treatment of idiopathic retroperitoneal fibrosis.

Idiopathic retroperitoneal fibrosis (RF) is a histologically benign, nonspecific inflammatory process of the fibroadipose tissue in the retroperitoneum with an unknown etiology. It may be complicated due to encasement and obstruction of the retroperitoneal structures. Tamoxifen has been known to be an effective agent in regression of desmoid tumors which include similar mesenchymal elements to those seen in RF. Herein, we reported a case of RF presented with ureteral obstruction and acute renal failure. The patient was successfully treated with tamoxifen.

Prevalence, awareness, treatment and control of hypertension in Turkey (the PatenT study) in 2003.

OBJECTIVE: To determine the distribution of blood pressure (BP) and prevalence, awareness, treatment and control of hypertension in Turkey (PatenT). DESIGN: A population-based cross-sectional epidemiology survey was carried out in 2003. SETTING: Twenty-six cities from seven geographical provinces of Turkey, with proportional representation of urban and rural populations. PARTICIPANTS: A two-stage stratified sampling method was used to select a sample of the adult population over 18 years of age. The total number of participants was 4910. INTERVENTIONS: Data collection and BP measurements were conducted by specifically trained physicians in the households of the participants. MAIN OUTCOME MEASURES: The mean systolic and diastolic BP levels, distribution of blood pressure, prevalence of hypertension (mean systolic BP>or=140 mmHg or mean diastolic BP>or=90 mmHg, or previously diagnosed and/or taking antihypertensive drugs), awareness, treatment and control of hypertension were assessed. RESULTS: The overall age-adjusted and sex-adjusted prevalence of hypertension in Turkey was 31.8%, and it was higher in women than in men (36.1 versus 27.5%, P<0.001). In the whole group, 32.2% had never had their BP measured. Overall, 40.7% of those with hypertension were aware of their diagnosis, only 31.1% were receiving pharmacologic treatment and only 8.1% had their BP under control. The subjects who were aware and treated had a control ratio of 20.7%. CONCLUSIONS: PatenT data indicate that hypertension is a highly prevalent but inadequately managed health problem in Turkey. There is an urgent need for population-based strategies to improve the prevention, early detection and control of hypertension.

Three siblings with steroid-resistant nephrotic syndrome: new NPHS2 mutations in a Turkish family.

Steroid-resistant nephrotic syndromes often are resistant to additional immunosuppressive agents and tend to progress to end-stage renal disease. Genetic studies in children with familial nephrotic syndrome have identified mutations in genes that encode important podocyte proteins. NPHS2 mutations are responsible for autosomal recessive familial focal segmental glomerulosclerosis (FSGS), and these mutations were detected in both familial and sporadic forms of FSGS. Interethnic differences were suggested to play a role in the incidence of these mutations. In this report, the cases of 3 siblings with steroid-resistant nephrotic syndrome who carry NPHS2 mutations (R238S and P118L) are presented.

tuberculous otitis media in a renal transplant recipient.

Tuberculous otitis media is a rare cause of chronic suppurative infection of the middle ear and a very uncommon form of extrapulmonary tuberculosis. Although there have been several case reports in the nonimmunosuppressive population of tuberculous otitis media, it has never been reported in an immunosuppressed allograft recipient. We present a case of diagnosed tuberculous otitis media after recurrent chronic otitis media treated several times with empiric antibiotic treatment. After the patient developed postauricular fistula and underwent surgical removal of granulation tissue, the diagnosis was made on the basis of histopathology and growth in culture of Ziehl-Neelsen. Clinical response promptly followed institution of antituberculous treatment including isoniazid, rifampicin, ethambutol, and pyrazinamide.

MPO-ANCA-associated pulmonary-renal vasculitis in a patient with diabetes mellitus.

Diabetes mellitus is one of the major causes of chronic renal failure. Typical findings of diabetic nephropathy are early hyperfiltration followed by microalbuminuria and overt proteinuria, resulting in a progressive decrease in glomerular filtration rate. Rapidly progressive glomerulonephritis has rarely been reported in patients with diabetes mellitus. Here, we describe a patient with MPO-ANCA-associated vasculitis, presenting with pulmonary-renal syndrome. Immunosuppressive treatment, including pulse methyl-prednisolone and cyclophosphamide, was administered and the disease was resolved.