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.

Effect of daily sodium intake on post-transplant 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.

Constrictive pericarditis after renal transplantation: three case reports.

INTRODUCTION: Pericardial exposure can be see in chronic kidney disease, but constrictive pericarditis (CP) development, which is usually present with signs of right-sided heart failure is rare. In renal transplant recipients CP can lead to graft dysfunction and serious liver disease. We present herein 3 such CP patients. PATIENT 1: A 37-year-old male patient with end-stage renal disease (ESRD) due to membranoproliferative glomerulonephritis was on chronic hemodialysis (HD). He underwent living donor kidney transplantation in 1995. In 2006 he was admitted with complaints of shortness of breath, weakness, and abdominal distention. PATIENT 2: A 17-year-old male patient with ESRD due to vesicoureteral reflux had 6 months of HD and underwent living donor kidney transplantation in 2008. Six months after transplantation, he showed leg edema, massive ascites, hepatosplenomegaly, and pretibial edema. PATIENT 3: A 52-year-old male patient was 21 years after HD initiation when cadaveric donor kidney transplantation was performed in August 2011. Four months after transplantation, he presented with a shortness of breath and fatigue. Echocardiography revealed 2-3 degree aortic regurgitation and increased pericardial brightness. CONCLUSION: All patients underwent right-sided heart catheterization, leading to a diagnosis of constrictive pericarditis, requiring total pericardiectom. Pathological examination of the pericardium showed typical diffuse fibrosis.

Low-density lipoprotein oxidizability and the alteration of its fatty acid content in renal transplant recipients treated with cyclosporine/tacrolimus.

Renal transplantation is widely used to treat patients with end-stage renal disease. Atherosclerosis is an important posttransplantation risk factor for renal transplant recipients. Subsequent to transplantation low-density lipoprotein (LDL) particles become susceptible to oxidative modification, which results in atherosclerosis. Therefore, the aim of our study was to investigate differences in the susceptibility of LDL particles to oxidation by analyzing LDL fatty acid levels among renal transplant recipients. The changes in lag phases and fatty acid levels of LDL were observed over 4 months among renal transplant recipients treated with Cyclosporine (CsA; n = 7) or Tacrolimus (FK-506; n = 9). We also analyzed cholesterol and triglyceride levels of patients and healthy controls. The lag phase at the 60th day after transplantation was significantly shorter than the results either before transplantation or among control subjects. In conclusion, a similar decrease in lag phase was observed in both above groups, but the FK-506-treated group showed a better lipid profile than the CsA-treated group.

Urinary tract infections following renal transplantation: a single-center experience.

BACKGROUND: Although infectious complications are the second most common cause of death after transplantation, there appears to be insufficient data regarding the impact of urinary tract infections (UTIs) on graft outcome and patient mortality and morbidity. In this study, we evaluated the incidence, risk factors, and long-term effects of UTIs on graft function. METHOD: We performed a retrospective cohort study reviewing the medical records of patients who received a renal transplant at our center from January 1999 to December 2006. All UTIs, risk factors, long-term graft function, graft loss, and death were recorded. Outcomes among patients with UTIs were compared with those without UTIs. RESULTS: Fifty-six of 136 patients (41.2%) had at least one UTI over a mean period of 38+/-25 months after transplantation. While there was a tendency toward graft loss among patients with UTIs (16.1% vs 6.3%, P=.08), there was no increased risk of death. The patients with UTIs displayed higher serum creatinine levels (1.7+/-1.4 vs 2.3+/-2.5 mg/dL, P=.07) compared to non-UTI patients in the long term. Upon multivariate analysis, female gender was the only risk factor for posttransplant UTIs. We did not determine any immunosuppressive drug as a risk factor for UTIs. The most frequent pathogens isolated in urine culture were Escherichia coli (n=72, 59.1%) and Klebsiella spp (n=21, 16.9%), and there were eight cases of bacteremia. CONCLUSION: UTIs are a frequent problem after kidney transplantation. Female recipients are at greatest risk. In the long-term, UTIs should be considered as a potential risk for poorer graft outcomes.

Acute cytomegalovirus infection complicated by venous thrombosis in a renal transplant recipient.

We report a case of simultaneous acute cytomegalovirus infection and venous thrombosis in a renal transplant recipient. On posttransplant month 3, the patient started complaining of left leg pain and swelling. Tibiopopliteal and femoral deep venous thrombosis were confirmed by Doppler ultrasonography. A serological test for CMV ELISA was strongly positive for IgM antibodies. Acute CMV infection was diagnosed by serum quantitative DNA polymerase chain reaction. Genetic predisposing risk factors for thrombosis (eg, protein C and S deficiency, factor V Leiden and prothrombin G20210A mutations, and antithrombin III deficiency) were not present. Results of tests for anticardiolipin antibodies, lupus anticoagulant, and antinuclear antibodies were also negative. No other clinical or biologic risk factors for thrombosis were detected in the patient. The patient responded well to intravenous gancyclovir and low-molecular weight heparin therapy. He was discharged in good condition. Our observation suggests that acute CMV infection may be the cause of a thrombotic event in renal transplant recipients.

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

INTRODUCTION: Posttransplant hypertension is a well-known risk factor for long-term allograft failure and mortality in kidney recipients. Although dietary sodium restriction is a widely recommended nonpharmacological measure for control of blood pressure (BP), no detailed investigation has been conducted regarding the impact of dietary sodium restriction on this condition. METHODS: Thirty-two patients on antihypertensive treatment completed the study. They were randomly divided into two groups: controls (group 1) versus strict sodium diet (group 2; 80 to 100 mmol sodium daily). After randomization, 24-hour urine for sodium measurement, BP, and allograft functions were recorded at baseline and after 3 months. BP treatment was reevaluated at each visit throughout the study. RESULTS: At baseline, there was no significant difference in age, sex, serum creatinine, systolic and diastolic BP, antihypertensive drugs, or 24-hour urinary sodium levels between the groups. After 3 months, daily urinary sodium excretion (from 190+/-75 to 106+/-48 mEq/d, P<.0001), systolic BP (from 146+/-21 to 116+/-11 mm Hg), and diastolic BP (from 89+/-8 to 72+/-10 mm Hg) had significantly decreased in group 2, while no significant changes were observed in group 1. CONCLUSION: Low sodium intake in combination with antihypertensive treatment appears to efficiently control BP in kidney allograft recipients with hypertension. Twenty-four-hour urinary sodium excretion should be checked regularly in these patients as a useful marker to indicate whether the patient complies with low sodium intake.

Mycobacterium tuberculosis infection in renal transplant recipients.

Mycobacterium tuberculosis (TB) infection is more common among renal allograft recipients compared with the general population due to immunosuppression. The epidemiological risk in a country is an important determinant of transplant TB after transplantation. We retrospectively analyzed 283 renal transplant recipients who underwent renal transplantation between 1990 and 2004. We evaluated the incidence, patient and disease characteristics, prognosis, and outcome of TB infection. Tuberculosis developed in 10 (seven men and three women of mean age of 41+/-9 years) among 283 patients (3.1%). All patients were culture-positive for M tuberculosis. Although pulmonary TB was the most common presentation in the general population, 50% of patients in the study group developed extrapulmonary TB. The mean elapsed time from renal transplantation was 38 months. Three patients (1%) developed TB in the first year after transplantation. All patients were treated with a quartet of anti-TB therapy. One patient developed isoniazid-related reversible hepatotoxicity. No acute allograft rejection occurred during the anti-TB therapy. Two patients (20%) with pulmonary TB died due to dissemination of the disease. In conclusion, extrapulmonary presentations of TB are more common among renal transplant recipients with the increased risk of mortality.

Klebsiella pneumoniae peritonitis shortly after kidney transplantation.

We report a case of spontaneous bacterial peritonitis caused by Klebsiella pneumoniae in a 34-year-old male recipient shortly after kidney transplantation. On posttransplant day 10, the patient started complaining of severe abdominal pain and nausea. Body temperature was 38.4 degrees C. The abdomen was diffusely tender with rigidity and rebound. Laboratory data showed a normal erythrocyte sedimentation rate and serum creatinine level but a slightly elevated C-reactive protein concentration and leukocytosis of 36,200 cells/mm(3) with 88% neutrophils. Explorative laparotomy revealed diffuse purulent peritonitis without an intraabdominal source of infection, such as intestinal perforation. The peritoneal fluid revealed greater than 1000/mm(3) white blood cells and many gram-negative bacilli. Fluid cultures yielded growth of Klebsiella pneumoniae. The patient responded to antibiotic therapy; he was discharged in good condition. This case report draws attention to the impaired host defense that may predispose to spontaneous bacterial peritonitis in renal transplant recipients and alerts the clinician to the possibility of this rare disease.

Long-term outcome of renal transplantation in patients with familial Mediterranean fever amyloidosis: a single-center experience.

Although recurrence of amyloid A deposition in the allograft can be seen in patients with secondary amyloidosis due to familial Mediterranean fever (FMF), renal transplantation remains to be a choice of treatment for end-stage renal disease. The aim of this study was to determine short- and long-term results of renal transplantation in patients with FMF amyloidosis. We compared the outcomes of 17 patients with FMF amyloidosis among 431 (3.9%) transplants with 209 control patients. We observed 93% and 94% graft and patient survivals at 1 year, and 89% and 90% at 5 years. Also, the mean serum creatinine levels at 1 and 5 years posttransplant were similar. Recurrence of amyloidosis was documented in two allograft recipients presenting with nephrotic range proteinuria (12%), one of whom lost the allograft due to recurrence. Eleven patients had FMF gene analysis. The results of MEFV mutation analyses were: M694V/M694V homozygote in six patients, M694V/EQ148 in one patient, M694V/V726A in one patient, 680M-I/E148Q in one patient. FMF gene analysis was negative in two patients. Recurrence was noticed in one patient with M694V/M694V, while the other did not have an FMF gene analysis. Colchicine was reduced in nine patients due to side effects. In conclusion, the long-term outcomes of transplantation in patients with amyloidosis secondary to FMF is similar to that in the general transplant population and maintenance colchicine, even at low dose, appears to effectively prevent recurrence of amyloidosis in the allograft.

Immunoglobulin deficiency in kidney allograft recipients: comparative effects of mycophenolate mofetil and azathioprine.

Mycophenolate mofetil (MMF) has commonly been substituted for azathioprine (AZA) in kidney transplantation and has been shown to have a greater effect on T cell function and also B cell function than AZA. Although immunoglobulin deficiency has been investigated in patients treated with protocols that include AZA, it has not extensively been studied in MMF-based immunosuppressive protocols. To evaluate this effect, we conducted a prospective study and recruited 49 patients. The patients received either AZA- (group 1) or MMF- (group 2) based therapy. A total of 17 patients in group 1 and 24 patients in group 2 completed the study. Immunoglobulin levels were evaluated before and in every month after transplantation for a 6-month period. Total infectious episodes were recorded and evaluated after 6 months in both groups. While no significant differences have been found in group 1, there were significant decreases in IgG, M, and A levels in group 2 after 6 months (IgG: 11.6+/-1.5-6.8+/-2.0 g/L, P<0.0001; IgM: 2.20+/-1.40-1.40+/-1.16 g/L, P=0.02; IgA: 1.40+/-0.70-1.07+/-0.86 g/L P=0.03). Two patients (11.7%) in group 1 and 11 patients in group 2 (45.8%) were found to have at least one low level of immunoglobulin (P=0.03). When the infectious complications were evaluated, the mean number of infection episodes in each patient was 1.3+/-1.6 and 0.5+/-0.7 for the MMF and AZA groups, respectively (P=0.06). Recurrent urinary tract infection developed in eight patients and seven of those were in group 2. In group 2, 7 of 11 patients with low immunoglobulin levels had recurrent urinary tract infection (63%), while no patient who had normal immunoglobulin levels developed any recurrent urinary tract infections (P<0.001). After 6 months, MMF was changed to AZA in these seven patients, who had both recurrent urinary tract infections and low immunoglobulin levels. All but one patient was found to have normal immunoglobulin levels after 3 months of conversion and only two episodes of infection were recorded during this period. We suggest that serum immunoglobulin levels can be monitored in patients taking MMF, and conversion from MMF to AZA may be an alternative for patients with low immunoglobulin levels and recurrent urinary tract infections.

Polyglandular endocrine failure in a patient with amyloidosis secondary to familial Mediterranean fever.

Familial Mediterranean fever (FMF) is 1 of the major causes of secondary amyloidosis. Renal involvement is the main clinical complication and it mostly presents with nephrotic syndrome and chronic renal failure. Although deposition of amyloid has been reported in several endocrine glands such as the adrenal, thyroid, and testes, clinically significant functional impairment is uncommon. Herein, we describe a patient in whom the diagnosis of FMF was based on molecular screening and who presented with recurrent hypoglycemic attacks and extensive amyloid deposition affecting various organ function including adrenal, thyroid, parathyroid, testes, intestinal system, and the heart.

Factors affecting the selection of a reversible or an irreversible contraceptive method in a developing country.

OBJECTIVES: To evaluate the factors that may affect the selection of a reversible or an irreversible contraceptive method. METHODS: In an urban area of a developing country, demographic characteristics, educational and income levels, and previously used contraceptive methods were retrospectively reviewed for 3 years from the files of women who had chosen reversible or irreversible contraceptive methods. Student's t test and the chi2 test were used to analyze the data obtained from the two groups of women. RESULTS: Out of a total of 8078 women, 595 (7.4%) selected surgical sterilization, while 7483 (92.6%) preferred reversible methods such as intrauterine devices (38.1%), combined oral contraceptives (13.9%), condoms (40%) and Norplant (0.6%). Compared to those who preferred reversible methods, the women with surgical sterilization had a higher mean age (33.9 +/- 4.2 years versus 29.6 +/- 3.9 years), mean gravidity (3.8 +/- 0.9 versus 2.3 +/- 1.2) and mean number of living children (2.6 +/- 0.8 versus 2.1 +/- 1.1) (p < 0.01). These women had also higher rates of high-school education (37.3% versus 30.1%) and previous modern contraceptive use (78.1% versus 71.2%) (p < 0.01). None of the women with surgical sterilization, but 1770 (33.0%) of those who chose reversible methods, had fewer than two living children. CONCLUSIONS: These data suggest that irreversible contraceptive methods tend to be chosen by older women with higher educational levels, who have decided that their family is complete and who have at least two children.

Carotid intima-media thickness and ACE-gene polymorphism in hemodialysis patients.

BACKGROUND: Carotid artery intima-media thickness (CIMT) has been used as a marker of atherosclerosis. An insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene is associated with various cardiovascular diseases. This study is aimed at evaluating early atherosclerotic involvement of carotid vessels and the relation to known risk factors and ACE gene I/D in hemodialysis (HD) patients. METHODS: We measured CIMT using high-resolution B-mode ultrasonography in 51 non-diabetic HD patients and in 70 age- and sex-matched healthy controls, and evaluated the factors influencing CIMT. An I/D polymorphism in intron 16 of the gene coding for ACE was analysed by polymerase chain reaction. RESULTS: The mean CIMT was significantly higher in HD patients than in healthy subjects (p<0.0001). In multiple regression analysis, independent risk factors for increased CIMT in HD patients were predialysis systolic blood pressure (p<0.001) and ACE D allele (p<0.01). CONCLUSIONS: The present data suggest that CIMT is enlarged in HD patients. The ACE gene seems to be a candidate for influencing the CIMT and might therefore be involved in an HD patient's predisposition to the development of atherosclerosis.

The impact of withdrawing ACE inhibitors on erythropoietin responsiveness and left ventricular hypertrophy in haemodialysis patients.

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors have the capability of decreasing left ventricular mass index (LVMI) in chronic haemodialysis (HD) patients. On the other hand, recent reports provide conflicting information regarding the impact of ACE inhibitors on responsiveness to recombinant human erythropoietin (rHuEpo), and there are no data about the effect of withdrawing ACE inhibitors both on rHuEpo response and LVMI in HD patients. METHODS: ACE inhibitors were switched to another antihypertensive medication in 23 out of 68 patients in our HD unit who were receiving both rHuEpo and an ACE inhibitor for more than 1 year. Blood pressure at the pre- and post-dialysis phases, haematocrit levels and rHuEpo doses were determined at the end of the first and of the third years, and the LVMI was determined at the end of the third year. Statistical analyses were done in 15 patients in whom the study could be completed. RESULTS: The mean (+/-SD) haematocrit level was increased from 26.3+6.4% to 29.8+/-6.3% at the first year (P<0.05), and to 29.4+/-6.5% at the third year (P<0.05 vs before), while the mean dose of rHuEpo was decreased from 208.3+/-99.0 UI/kg/week to 141.0+/-91.8 at the first year (P=0.01), and to 141.4+/-81.0 at the third year (P=0.01 vs before). Administration of rHuEpo had been stopped in two patients at the end of the first year. The mean blood pressure level and the mean LVMI were not changed (P>0.05 vs before). There were no significant changes in dialysis parameters, iron status, plasma renin activities, and levels of aldosterone, intact parathyroid hormone, aluminum and erythropoietin. CONCLUSION: The findings of this small uncontrolled study indicate that withdrawal of ACE inhibitors in hypertensive chronic HD patients receiving rHuEpo may result in an increase in haematocrit level, and a decrease in dose of rHuEpo without any significant changes in the blood pressure level and LVMI. Controlled prospective studies are needed to clarify this issue.

Factors affecting the contraceptive choice in a developing country.

OBJECTIVES: To evaluate the factors affecting the contraceptive choice of women in a developing country. METHODS: Demographic characteristics, education and income level, previous and current contraceptive choices of the women from a maternity and a university hospital were retrospectively reviewed for 2 years. The data obtained from the two hospitals were analyzed by Student's t- and chi2-tests. RESULTS: Family planning services were offered to 651 and 7427 women in the university and the maternity hospital, respectively. Although the mean ages and income levels of the women in two centers were similar, the women in the university hospital had lower mean gravidity and mean number of living child, while they had higher education level and previous modern contraceptive use (P < 0.05-0.001). The women in the university hospital more frequently preferred combined oral contraceptive and surgical sterilization, while those in the maternity hospital chose condom and intrauterine device (P < 0.01-0.001). CONCLUSIONS: Women with higher education level had a lower number of pregnancies and living children due to more frequent use of previous effective contraception and they chose combined oral contraceptives and irreversible methods more frequently.