Preoperative evaluation of hilar vessel anatomy with 3-D computerized tomography in living kidney donors.

OBJECTIVES: Digital subtract angiography is the gold standard for anatomic assessment of renal vasculature for living renal donors. However, multidetector-row computerized tomography (MDCT) is less invasive than digital subtract angiography and provides information of kidney stones and other intra-abdominal organs. In this study, preoperative MDCT angiography results were compared with the peroperative findings to evaluate the accuracy of MDCT for the evaluation of renal anatomy. METHODS: From December 2002 to May 2007, all 60 consecutive living kidney donors were evaluated with MDCT angiography preoperatively. We reported the number and origin of renal arteries, presence of early branching arteries, and any intrinsic renal artery disease. Renal venous anatomy was evaluated for the presence of accessory, retroaortic, and circumaortic veins using venous phase axial images. The calyces and ureters were assessed with delayed topograms. The results of the MDCT angiography were compared with the peroperative findings. RESULTS: A total of 67 renal arteries were seen peroperatively in 60 renal units. Preoperative MDCT angiography detected 64 of them. The two arteries not detected by MDCT had diameters less than 3 mm. Anatomic variations were present in nine veins, five of which were detected by CT angiography. Sensitivity of MDCT angiography for arteries and veins was 95% and 93%, respectively. Positive predictive values were 100% for both arteries and veins. CONCLUSION: MDCT angiography offers a less invasive, rapid, and accurate preoperative investigation modality for vascular anatomy in living kidney donors. It also provides sufficient information about extrarenal anatomy important for donor surgery.

Utility of the Doppler ultrasound parameter, resistive index, in renal transplant histopathology.

BACKGROUND: Doppler ultrasonography is routinely used by many clinicians during long-term follow-up to identify high-risk patients without diagnosing the exact cause of graft dysfunction. Despite a number of studies showing a correlation between intrarenal resistive index (RI) and renal function in patients with kidney diseases, correlations between RI and renal histopathologic characteristics have not been sufficiently evaluated in renal transplant recipients. The aim of this study was to examine this relationship in grafted kidneys. PATIENTS AND METHODS: The intrarenal RI was retrospectively compared with biopsy findings in 28 kidney recipients. All renal biopsy specimens were reviewed by light microscopy and immunofluorescence staining. For glomerulosclerosis, we considered the percentage of glomeruli showing this change; for interstitial fibrosis/tubular atrophy and interstitial infiltration, we graded abnormalities according to the methods of Kliem et al (Kidney Int 49:666, 1996). RESULTS: The percentage of globally sclerosed glomeruli was significantly greater among patients with RI values higher than 0.75 than below this level (23% vs 47%; P = .022). Patients with grade 1 interstitial fibrosis and tubular atrophy (n = 14) showed lower RI values (0.68 +/- 0.03 vs 0.74 +/- 0.06; P = .047) than those with grade 3 fibrosis (n = 12). Similarly, lower RI values (0.66 +/- 0.02 vs 0.73 +/- 0.05; P = .014) were observed among patients with grade 1 (n = 13) compared with grade 3 interstitial infiltration (n = 13). CONCLUSION: RI seemed to provide a prognostic marker for the graft rather than yielding an exact diagnosis of renal graft dysfunction.

Utility of c2 monitoring in prediction of diastolic dysfunction in renal transplant recipients.

BACKGROUND: A number of experimental studies have suggested that cyclosporine (CsA) toxicity induces cardiac modifications which may cause diastolic dysfunction over the course of time. Doppler echocardiography with tissue Doppler imaging (TDI) could consistently detect diastolic dysfunction. The purpose of this study was to assess diastolic dysfunction using C2 monitoring of CsA exposure in stable renal transplant patients. PATIENTS AND METHODS: Seventy-eight kidney recipients including 42 men and 36 women of overall mean age of 52 +/- 9 years were obtained in 47 living and in 31 cases from cadaveric donations over 12 or more months after transplantation using cases from CsA, mycophenolate mofetil, and steroid. C2 levels were measured by an enzyme multi-immune assay technique. The patients underwent conventional and Doppler echocardiography with TDI. RESULTS: The patients were divided into 2 groups according to C2 levels less than 500 mug/L (group 1, n = 40) versus greater than 500 mug/L (group 2, n = 38). The demographic parameters, serum creatinine and lipid levels, systolic and diastolic blood pressures, number and type of antihypertensive medications, and conventional echocardiographic parameters did not differ significantly between the groups. However, group 1 patients showed significantly higher isovolumic relaxation time (109 +/- 27 vs 86 +/- 14 ms), early diastolic deceleration time (189 +/- 52 vs 137 +/- 59 ms), and lower values of E velocity (56 +/- 32 vs 92 +/- 27 cm/s) and E/A ratios (0.81 +/- 0.23 vs 1.15 +/- 0.46) than group 2. TDI studies revealed significantly lower E'/A' (0.76 +/- 0.25 vs 1.09 +/- 0.32, P < .05) in group 1 versus group 2. CONCLUSION: The data suggested that the higher C2 levels may induce diastolic dysfunction in the hearts of kidney recipients without impairment of contractile performance.

The role of proinflammatory cytokine gene polymorphisms for development of insulin resistance after renal transplantation.

BACKGROUND: Insulin resistance, a frequent prediabetic metabolic complication after renal transplantation, is generally linked to immunosuppressive drugs including corticosteroids, cyclosporine (CsA) or tacrolimus, as well as to age, cadaveric donors and ethnic factors. Cytokines are known to be inflammation modulatory substances that contribute to metabolic derangements after transplantation. The present study investigated the effects of cytokine gene polymorphisms on insulin resistance in renal transplant recipients. PATIENTS AND METHODS: Sixty-one renal transplant recipients (37 men, 24 women; mean age: 39.3 +/- 10.8 years) who attended regular clinical visits without a known history of diabetes were enrolled in the study. All patients were on a regimen of steroid, CsA, and mycophenolate mofetil. Venous blood samples were collected for biochemical analyses after an overnight fast at 08:00 pm. CsA trough levels, C-reactive protein, and fibrinogen were also estimated. Additional 10 mL of blood was withdrawn into an ethylenediamine tetraacetic acid-containing tube to determine cytokine genotypes (tumor necrosis factor-alpha [TNF-alpha] -238 G/A, transforming growth factor-beta [TGF-beta] codon 10 -869 T/C). Insulin resistance was calculated by the homeostasis model assessment (HOMA) method using the values of fasting blood glucose (FBG) and insulin levels. Anthropometric indices as well as body height, weight, waist and hip circumferences were measured simultaneously to calculate body mass index (kg/m2) and waist-to-hip ratio. Impaired fasting glucose (IFG) was described as an FBG > or = 110 but < 126 mg/dL. RESULTS: IFG was detected in 27.9% of this study group. The HOMA index was significantly higher among patients with IFG compared with normal FBG (NoGT) (6.3 +/- 4.5 vs 3.7 +/- 1.5; P = .01). Neither FBG and insulin nor HOMA values correlated with antrophometric, metabolic, or inflammatory parameters. Cytokine genotype allele frequencies, age, sex, immunosuppressive and antihypertensive drug type and doses, CsA trough levels, and donor source (cadaveric/living) were similar for patients with IFG and NoGT. Mutant allele carrier genotypes (AA + GA) for TNF-alpha -238 G/A showed higher fasting insulin (14.0 +/- 7.9 vs 34.1 +/- 17.7 microIU/mL; P = .04) and HOMA (4.01 +/- 2.01 vs 7.95 +/- 5.44; P = .002) levels than GG homozygote subjects. FBG, HOMA, and other metabolic and anthropometric indices were similar between TGF-beta codon 10 -869 T/C genotypes. The daily dose of steroid (mg/d) and A allele frequency for TNF-alpha -238 G/A genotype were significant predictors of HOMA index in linear regression analysis. CONCLUSION: The present study revealed that beside the daily dose of steroids, TNF-alpha -238 G/A genotype may contribute to insulin resistance in renal transplant recipients. Further investigations may highlight the effects of cytokine gene heterogenity on insulin resistance in those patients.

Effects of angiotensin converting enzyme and angiotensin II receptor inhibition on impaired fibrinolysis in systemic hypertension.

Abnormalities in fibrinolysis have been reported in hypertension. Angiotensin converting enzyme (ACE) inhibitors have been shown to improve altered fibrinolytic balance in hypertensive patients. It has not been documented, however, whether this is due to a decrease in angiotensin II (Ang-II) generation or is a consequence of elevated local levels of bradykinin. Accordingly, the aim of this study was to determine the effects of an ACE inhibitor (perindopril) and an Ang-II receptor antagonist (losartan) on fibrinolytic kinetics. We have examined the serum levels of the plasminogen activator inhibitor type-1 (PAI-1) antigen and activity, tissue plasminogen activator (t-PA) antigen and activity, soluble thrombomodulin (sTM), and tissue factor pathway inhibitor (TFPI) before and after reaching the target blood pressure (<140/90 mm Hg) in 13 hypertensive patients receiving perindopril (mean age 40+/-11 years, 6 women, 7 men) and in 12 patients receiving losartan (mean age 38+/-9 years, 6 women, 6 men). We also compared the baseline fibrinolytic activity of hypertensive patients with that of 12 normotensive control persons (mean age 40+/-9 years, 6 women, 6 men). The mean basal plasma levels of PAI-1 antigen, PAI-1 activity, and sTM were significantly higher in the hypertensive patients than in normal controls (P<.005). The values of other analytes were similar in both groups. Increased plasma levels of PAI-1 antigen, PAI-1 activity, and sTM were reduced in patients after they were given perindopril and losartan (P<.005); the reductions in losartan-receiving group were more pronounced (P<.05). There were no significant effects on the plasma levels of t-PA antigen, t-PA activity, and TFPI in patients receiving the two therapeutic regimens (P>.05). In conclusion, chronic hypertension is associated with hypofibrinolysis. The beneficial effect of ACE inhibitors on fibrinolysis seems to be related to the blockade of Ang-II, and increased kinin activity does not appear to play a major role.

Evidence for the role of dialysis hypoxemia in the pathogenesis of hemodialysis-induced rise in tissue-type plasminogen activator.

It is well known that hemodialysis (HD) causes a rise in plasma tissue-type plasminogen activator (t-PA). Although there have been several suggested mechanisms responsible for this effect of HD, the precise cause has not been well understood yet. Another complication of HD, when performed with acetate-containing dialysate, is hypoxemia, which is commonly observed during the first hour of the session. The purpose of this study was to investigate the relationship between dialysis hypoxemia and HD-induced t-PA changes during the first two hours of HD. HD caused significant increase in plasma t-PA antigen levels. When individual t-PA profiles versus time were examined, two patterns were observed. Whilst ten subjects (%56) experienced minimal or no increase, t-PA antigen level of the remaining eight subjects began to rise at 30 minutes and continued at that level up to 90 minutes, when the last samples were drawn. The courses of pO2 were also different; whilst the former group had "early-onset and short-term" hypoxemia, the latter had "late-onset and prolonged" hypoxemia. The amount of increase in t-PA antigen and the amount of decrease in pO2 were correlated at 60 and 90 minutes of the HD session. Thus, it is concluded that dialysis hypoxemia may contribute to HD-induced rise in plasma t-PA levels. Further studies comparing different dialysates and dialyser membranes are required to confirm this hypothesis.

Thrombopoietin and thrombospondin in renal allograft recipients.

Recipients of renal transplants appear to be at increased risk of thromboembolic events. Despite accumulating evidence for the hyperreactivity of platelets, the primary regulator of thrombopoiesis, thrombopoietin (TPO), has not yet been studied in renal transplant recipients. Thus, the aim of the present study was to quantify the levels of TPO and to assess its contribution to increased platelet reactivity in recipients of renal allografts. Serum concentrations of thrombospondin (TSP) were also determined in patients undergoing renal transplants in order to evaluate the role of this multifunctional protein in platelet hyperaggregability. Serum levels of TPO were significantly lower in renal transplant recipients (n = 27) than in healthy controls (30.8+/-20.6 pg/ml versus 129.9+/-113.6 pg/ml, P = 0.001). Serum concentrations of TPO were correlated neither with serum levels of creatinine nor duration of transplantation. However, levels of TPO were negatively correlated with platelet counts (r = -0.50, P = 0.007) in recipients of renal transplants. Plasma levels of TSP were higher in renal transplant patients than in the control group (104.5+/-54.7 ng/ml versus 63.4+/-41.5 ng/ml, P = 0.003). No significant correlation was found between levels of TPO and TSP. We conclude that, rather than the allograft function, the platelet mass determines the levels of TPO in recipients of renal transplants. Despite the low serum levels of TPO, and increased concentrations of TSP, TPO might still play a role in the hyperaggregability of platelets in patients undergoing renal transplants.

Rapidly progressive glomerulonephritis associated with hepatitis C virus infection.

Glomerular disease often accompanies a wide variety of liver diseases, including acute or chronic hepatitis. A striking association between hepatitis B virus and glomerulonephritis particularly membranous glomerulonephritis has been reported by various authors. It is not surprising, therefore, that hepatitis C virus (HCV) infection has been recently associated with the development of various types of glomerulonephritis. The principal type of glomerulonephritis associated with HCV infection is either cryoglobulinemic or non-cryoglobulinemic membranoproliferative glomerulonephritis. However, other types of glomerular lesions were seen in the clinical course of HCV infection. We report a rare case of a 20-year-old woman who developed rapidly progressive glomerulonephritis (RPGN) during the course of the active HCV infection. Whether this case represents a true association or a coincidental association is not known.

Cyclical acute renal failure due to bilateral ureteral endometriosis.

Endometriosis is a common disease but ureteral involvement is relatively rare. Ureteric endometriosis is mostly unilateral. Endometriotic ureteral obstruction is a serious event commonly diagnosed late and therefore associated with a major risk of hydronephrotic renal atrophy. We present the cyclical acute renal failure associated with menstruation in a patient who developed severe bilateral ureteral obstruction due to endometriosis. Physicians should be aware of this uncommon but serious manifestation of endometriosis, especially if the clinical presentation is cyclical acute renal dysfunction in a premenopausal woman.

Determinants of soluble CD23 antigen levels in hemodialysis patients: effect of 1.25 dihydroxyvitamin D3 and recombinant human erythropoietin treatment.

BACKGROUND: The immunodeficiency of end-stage renal disease (ESRD) paradoxically coexists with T cell and monocyte activation. In spite of well known defective antibody responses in ESRD, the functional status of B cells in the immune system dysregulation of uremia is still controversial. Soluble CD23 (sCD23) antigen is a recently identified B cell activation marker and is also involved in T cell activation process. Effects of parathyroid hormone (PTH), red blood cells and ferritin on T and B cell functions have been shown both in vivo and in vitro. PATIENTS AND METHODS: In this study, serum levels of sCD23 in hemodialysis patients were determined to evaluate the functional status of B cells and possible linkages between this cytokine and PTH levels, ferritin levels, red blood cell counts were investigated. RESULTS: Serum sCD23 levels were significantly elevated in hemodialysis patients relative to healthy controls (12.5+/-8.4 micro/l vs. 2.4+/-1.1 micro/l, p<0.001). Serum sCD23 levels were negatively correlated with red blood cell count (r = -0.61, p = 0.009) and serum PTH levels (r = -0.62, p = 0.008), while positively correlated with serum ferritin levels (r = 0.63, p = 0.007) in hemodialysis patients. We also investigated the immunumodulator effects of 1.25 dihydroxyvitamin D3 (1.25OHD3) and recombinant human erythropoietin (rHu-Epo) treatment in hemodialysis patients. 1.25OHD3 treatment for eight weeks did not change serum sCD23 levels in hemodialysis patients (n = 8). On the other side, rHu-Epo administration for 16 weeks led to a decrease in serum sCD23 levels (17.7+/-8.6 microg/l vs. 9.8+/-3.5 microg/l, p = 0.007) in these patients (n = 9). CONCLUSION: These results suggests that similar to T cells, B cells are activated in uremia and the degree of this activation is correlated with red blood cell count, serum parathyroid hormone levels and iron status of the hemodialysis patients. Moreover, B cell activation could be altered by recombinant human erythropoietin therapy in hemodialysis patients.

Analgesic intolerance with or without bronchial asthma: is there a marker?

BACKGROUND: The prevalence of analgesic intolerance (AI) is less than 1% in the general population and about 10% in adult asthmatics, in whom the disease tends to be more severe. OBJECTIVE: A possible clinical-laboratory marker was sought that would differentiate patients who have AI with/without asthma, AI with asthma, and AI without asthma from the healthy subjects. METHODS: In the survey, 66 analgesic-intolerant patients (36 having asthma) were compared with 50 healthy subjects using a nickel patch-test, 65 patients (39 having asthma) with 55 healthy subjects for the presence of a genetic marker (A38G and A444C SNPs in CC16 and LTC4S genes), and 32 patients (14 having asthma) with 118 healthy subjects for presence and frequency of human leukocyte antigens (HLA). RESULTS: The mean age of the patients with AI with/without asthma and the healthy subjects for the nickel patch-test group, genetic marker group, and the HLA group was 39.8 +/- 10.5 and 33.3 +/- 11.1, 41.5 +/- 11.6 and 38.1 +/- 13.4, and 39.4 +/- 12.5 and 41 +/- 2.6, respectively. The frequency of the females in the same groups, in the same order, was 72.7% and 54%, 81.5% and 62%, and 71.9% and 59.3%, respectively. The frequency of positive nickel patch-test results and the A38G and A444C frequency in CC16 and LTC4S genes were not significantly different (p > 0.05). The frequency of HLA antigens HLA-A3, -B52, -DR16, -DQ5, -DQ8 and -DQ9 were significantly higher; and -A24, -B35, -B44, -DQ6 and -DQ7 were significantly lower in the AI group with/without asthma compared to the control group (p < 0.05). CONCLUSION: As a result, nickel patch-test positivity and the genes which we have studied do not seem to be markers for AI with/without asthma. However, there might be a relation between AI with/without asthma and the types of the HLA system. Further surveys are needed with other genes and possible markers.

Prediction of renal allograft function with early Doppler ultrasonography.

INTRODUCTION: Doppler ultrasonography (USG) is an useful, noninvasive diagnostic tool for the management and follow-up of the transplanted kidney. However, it is believed that the value of Doppler USG is limited to discrimination of acute rejection episodes. We tested whether early Doppler USG findings were predictive of 1-month and 1-year allograft functions in noncomplicated renal transplant recipients (RTRs). PATIENTS AND METHODS: Resistive index (RI) and pulsatile index (PI) values obtained by doppler USG within the first week of transplantation were correlated with allograft function at 1 month and 1 year in 45 (10 women, 35 men, mean age: 27 years) noncomplicated cases. Patients with complications during the first posttransplant year were not included. RESULTS: There was a negative correlation between both RI and PI with creatinine clearance values at 1 month and at 1 year posttransplant. There was a significant decline in allograft function among cases with either RI > or = 0.7 or PI > or = 1.1. Patients with impaired allograft function have higher RI and PI values. CONCLUSION: Renal allograft survival is influenced by many factors. However, no reliable simple parameter has been identified to predict long-term outcome. Doppler USG performed during the early transplantation period with calculation of RI and PI may have a predictive value to forecast early and long-term outcomes of noncomplicated kidney transplants.

Hypertension because of an arteriovenous fistula between the right renal artery and the inferior vena cava secondary to a gunshot wound: a case report.

A case of a renovascular hypertension due to an arteriovenous fistula between the right renal artery and the IVC secondary to a gunshot wound 8 years previously is reported. The diagnosis was made initially by the clinical signs of a continuous bruit heard over the anterior abdomen and by the characteristic findings of diastolic hypertension. Diagnosis was confirmed by abdominal aortography. In the operation, the right renal artery was ligated and divided proximally between the aorta and the aneurysm and distally beyond the fistulous communication and a Gore-Tex graft was anastomosed between distal part of the renal artery and abdominal aorta. The result was confirmed by postoperative aortography and by disappearance of the preoperative physical findings. The present case, to our knowledge, is the sixth in the literature.

Increased erythropoietin response to venesection in erythrocytosic renal transplant patients.

Anaemia of end-stage chronic renal failure improves following successful kidney transplantation. However, erythrocytosis occurs in 6.8-17.3% of transplanted patients. Mechanism of post-transplant erythrocytosis (PTE) and its erythropoietin (Epo) dependence are still controversial. Firstly, we compared basal serum Epo levels of 10 PTE patients, 14 non-erythrocytosic renal transplant (non-PTE) patients and 12 healthy blood donors. Then we performed venesection in PTE patients and healthy blood donors and compared their Epo response to venesection 5 hours later. The mean basal serum Epo of 24.3 mU/ml was significantly higher in the PTE group than the 10.8 mU/ml in the non-PTE and 8.6 mU/ml in the healthy blood donor group (p < 0.01). Epo levels in the non-PTE group did not differ significantly from those of healthy blood donors (p > 0.05). Following venesection the mean serum Epo levels increased significantly in both groups, from 24.3 mU/ml to 67.7 mU/ml (p < 0.001) in the PTE group and from 8.6 to 12.1 mU/ml (p < 0.01) in the healthy blood donor group, but the increment in the PTE group was more marked. We conclude that PTE patients have elevated basal serum Epo levels and there is a feedback regulation of Epo secretion in these patients like in healthy blood donors, but in an exaggerated way.

Protein Z levels in haemodialysis patients.

Protein Z (PZ) is a vitamin K-dependent protein isolated from human and bovine plasmas. Although the exact role of PZ in the haemostatic system is presently unknown, it is suggested that PZ deficiency may cause bleeding tendency. Haemostatic alterations in end-stage renal failure (ESRF) are certainly complex and involve several abnormalities in the coagulation and fibrinolytic system. In order to elucidate the detail of the haemostasis in ESRF, we aimed to investigate PZ activity in haemodialysis patients. Therefore, we compared plasma PZ levels in 10 haemodialysis patients (6 M, 4 F, mean age 36+/-11) and 10 healthy normal controls (5 M, 5 F, mean age 34+/-8) in this study. We found mean plasma PZ levels in haemodialysis patients and healthy controls 6.95+/-2.93 microg/ml and 3.06+/-0.81 microg/ml, respectively (p<0.005). Increased level of PZ which influences the action of thrombin on its protein substrates and inhibitors may contribute to the haemostatis alterations in ESRF patients, in addition to other well known abnormalities in the coagulation and fibrinolytic system.

Gingival health status in renal transplant recipients: relationship between systemic inflammation and atherosclerosis.

Cardiovascular disease (CVD) is the leading cause of mortality in renal transplant recipients (RTR). Systemic and periodontal inflammation has been suggested to have a possible role in the development of atherosclerosis. In the present study, we aimed to investigate the relationship between gingival health status, inflammation and atherosclerosis in RTRs. Eighty-three RTR (50 male, 33 female) were enrolled in the study. Routine biochemical analyses, serum lipoproteins, C-reactive protein, fibrinogen, homocystein, parathyroid hormone (PTH) and cyclosporin A (CsA) trough levels were studied. All patients had 24-h ambulatory blood pressure monitoring and B-mode ultrasound of the common carotid arteries. Gingival status was evaluated by the Löe and Silness gingival index (GI). Mean GI value was 2.3 +/- 0.5. Fifty patients (60.3%) had GI value >or= 2.1 (severe gingivitis; group A). Thirty-three patients (39.7%) had GI value < 2.1 (no or moderate gingivitis; group B). Age, carotid intima-media thickness (CIMT) and mean time on dialysis before transplantation were significantly higher in group A than in B. Systemic inflammation markers were not different between group A and group B. Mean CIMT was positively correlated with GI (r = 0.425; p = 0.001) and negatively correlated with high-density lipoprotein cholesterol (r = -0.256; p = 0.023). After the correction for confounding variables, mean CIMT was still significantly correlated with GI (r = 0.376, p = 0.02). In RTR, gingival inflammation seems to be associated with CIMT in the absence of systemic inflammation. Thus, gingivitis may, in part, play a role in the development of systemic atherosclerosis without causing any aggravation in systemic inflammatory response.

The expanding spectrum of a disease. Behçet's disease associated with amyloidosis.

In this report, we present a series of 6 patients with Behçet's disease (BD) associated with amyloidosis whose illnesses date back at least 4 years. In all the cases, nephrotic syndrome heralded the onset of amyloidosis, which was diagnosed by percutaneous kidney biopsies. After the diagnosis of amyloidosis, all subjects received colchicine, and steroids were discontinued. Three patients have benefited from treatment. It was suggested that amyloidosis may be an intrinsic feature of BD or that the suppurative lesions may play a role in the accumulation of amyloid in the tissues. The literature was reviewed and discussed.