Tuncay Aki

Polymorphisms of glutathione S-transferase genes (GSTM1, GSTP1 and GSTT1) and bladder cancer susceptibility in the Turkish population

Abstract. We investigated the effect of the GSTM1 and GSTT1 null genotypes, and GSTP1 313 A/G polymorphism on bladder cancer susceptibility in a case control study of 121 bladder cancer patients, and 121 age- and sex-matched controls of the Turkish population. The adjusted odds ratio for age, sex, and smoking status is 1.94 [95% confidence intervals (CI) 1.15–3.26] for the GSTM1 null genotype, and 1.75 (95% CI 1.03–2.99) for the GSTP1 313 A/G or G/G genotypes. GSTT1 was shown not to be associated with bladder cancer. Combination of the two high-risk genotypes, GSTM1 null and GSTP1 313 A/G or G/G, revealed that the risk increases to 3.91-fold (95% CI 1.88–8.13) compared with the combination of the low-risk genotypes of these loci. In individuals with the combined risk factors of cigarette smoking and the GSTM1 null genotype, the risk of bladder cancer is 2.81 times (95% CI 1.23–6.35) that of persons who both carry the GSTM1-present genotype and do not smoke. Similarly, the risk is 2.38-fold (95% CI 1.12–4.95) for the combined GSTP1 313 A/G and G/G genotypes and smoking. These findings support the role for the GSTM1 null and the GSTP1 313 AG or GG genotypes in the development of bladder cancer. Furthermore, gene-gene (GSTM1-GSTP1) and gene-environment (GSTM1-smoking, GSTP1-smoking) interactions increase this risk substantially.

Carotid intima–media thickness in children and young adults with renal transplant: Internal carotid artery vs. common carotid artery

Abstract:  Cardiovascular diseases are the main causes of morbidity and mortality following renal transplantation. Atherosclerotic structural changes, which can be detected by high‐resolution B‐mode ultrasonography, begin before clinical findings. However, little is known about the extent of these abnormalities in children after renal transplantation. We aimed to determine early structural changes of large arteries in renal transplant recipients without cardiovascular disease and to evaluate the role of clinical and laboratory features on IMT of carotid arteries. IMT and hemoglobin, serum levels of creatinine, acute phase proteins, lipid profile, and homocysteine were examined in 24 asymptomatic renal transplant recipients (median age 16.5 yr; range 8–25), and 20 healthy controls (median age 16 yr; range 9–24). CCA and ICA were evaluated in patients and controls with a high‐resolution B‐mode ultrasonography in multiple projections to optimize detection of carotid IMT. Measurement of IMT of both CCA [0.36 mm (range 0.16–0.48) vs. 0.28 mm (range 0.21–0.35), p < 0.001] and ICA [0.27 mm (range 0.16–0.48) vs. 0.22 mm (range 0.1–0.26), p < 0.001] were significantly higher in renal recipients than in healthy controls. Among several parameters assessed, only significant correlations were found between duration of CRF, duration of dialysis prior to transplantation and ICA‐IMT (p = 0.06 and p = 0.02, respectively) and between mean past serum calcium–phosphorus ion product and CCA‐IMT (p = 0.002). In conclusion, our observations indicate that vascular changes begin early in the course of CRF and are directly related to time on CRF and dialysis. These changes can be detected by measuring CCA/ICA‐IMT ultrasonographically. We suggest that early renal transplantation can potentially avoid long‐term cardiovascular events in children with end stage kidney disease.

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.

Use of Mesenchymal Stem Cells and Darbepoetin Improve Ischemia-Induced Acute Kidney Injury Outcomes

Background: Interest has recently been focused on the possible role of bone marrow-originating stem cells and the therapeutic role of erythropoietin in the recovery of ischemia-induced acute kidney injury (AKI). The aim of the present study was to compare treatment with mesenchymal stem cells (MSCs) to treatment with darbepoetin-α (DPO) or both concomitantly in a rat model of ischemia/reperfusion (I/R) AKI. Methods: Forty male Sprague-Dawley rats were included, and 28 of them were randomly assigned to controls (treated with serum physiologic) or one of the three treatment groups treated with either DPO, MSCs, or both (MSCs and DPO concomitantly) after the induction of I/R injury. Hematocrit, serum creatinine, and BUN levels were obtained at 0, 24, 48, and 72 h of surgery, and renal tissue was obtained at 72 h after nephrectomy for histological analysis. Tissue injury was quantified by standardized histological scoring systems, using light and electron microscopes. Results: Treatment with MSCs or DPO improved renal function compared with controls. However, the improvement observed in renal function in the MSC/DPO group was better than that in the other groups. Histological analysis demonstrated that tissue injury was significantly decreased in rats in the MSC or DPO groups compared to that of the controls; however the best recovery was observed in rats treated with MSCs and DPO concomitantly. Conclusion: These results suggest that concomitant application of DPO and MSCs may be a potential novel renoprotective therapy for patients after having sustained an ischemic renal insult.

Association of Serum Lipid Profile and Arteriovenous Fistula Thrombosis in Maintenance Hemodialysis Patients

Background: Vascular access thrombosis represents a major cause of morbidity in the hemodialysis population. The role of serum lipid profile in access thrombosis is not sufficiently established. The aim of this study was to investigate the association between serum lipid profile and native arteriovenous fistula (AVF) thrombosis. Methods: Clinical files of 99 maintenance hemodialysis patients were reviewed retrospectively for 3 years. Serum lipid profile, albumin and C-reactive protein (CRP) were measured. Catheter angiography was performed in patients with AVF dysfunction and AVF thrombosis. Results: Patients with AVF thrombosis and patent AVF had similar serum levels of total cholesterol and triglyceride levels. However, patients with AVF thrombosis had significantly lower low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and albumin and higher serum CRP levels than patients with patent AVFs. Conclusions: Serum levels of lipid subfractions are associated with AVF thrombosis in maintenance hemodialysis patients. Larger and prospective cohort studies are needed to confirm these observations.

Effect of transurethral resection on serum free/total prostate-specific antigen levels in patients with benign prostatic hyperplasia.

OBJECTIVES Transurethral resection of the prostate (TURP) can cause elevation of total serum prostate-specific antigen (PSA). However, the effect of these procedures on free PSA and percent free PSA is still unknown. The aim of this study was to investigate the effect of TURP on serum total PSA, free PSA, and free/total (f/t) PSA ratio in patients with benign prostatic hyperplasia (BPH) and to determine the reliability of f/t PSA ratio after such interventions. METHODS Fifty-three patients with BPH who underwent TURP because of severe bladder outlet obstruction symptoms were included in this study. All patients underwent digital rectal examination and transrectal ultrasound (TRUS), and routine hematologic (complete blood count) and serum biochemical tests, urine analysis, and a peak urinary flow test were performed. Serum total PSA and free PSA levels were determined 1 hour before and 24 hours after TURP by using enzyme immunometric assay. Preoperative and postoperative free and total PSA and f/t PSA ratio were statistically compared. RESULTS Although postoperative total PSA and free PSA increased significantly compared with preoperative values (P <0.001 and P = 0.024, respectively), the difference between preoperative and postoperative f/t PSA ratios was not statistically significant (P = 0.103). CONCLUSIONS Finding no significant change in f/t PSA ratio, although there is a significant increase in the serum levels of total and free PSA, suggests to us that f/t PSA ratio may be a more reliable parameter in the early period after such interventions as TURP.

A Novel Immunosuppressive Agent, Sirolimus, in the Treatment of Kaposi's Sarcoma in a Renal Transplant Recipient

Renal transplant recipients are susceptible to Kaposis sarcoma (KS) because of treatment with immunosuppressive drugs. Sirolimus, a new immunosuppressive agent, has been successfully used for immune-suppression in kidney transplant recipients. Several studies have shown the potential role of sirolimus to inhibit progression of KS in kidney-transplant recipients. This report details a kidney-transplant recipient with cutaneous KS who had a complete remission in response to sirolimus therapy.

Elevated urinary angiotensinogen a marker of intrarenal renin angiotensin system in hypertensive renal transplant recipients: does it play a role in development of proteinuria in hypertensive renal transplant patients?

The aim of this study was to evaluate the relationship of local intrarenal renin angiotensin system (RAS) with hypertension and proteinuria in renal transplant recipients. Sixty‐nine nondiabetic renal transplant recipients (39 male, mean age: 36.3 ± 11.5 years) were included in this study. All patients were in stable condition with GFR greater than 30 ml/min/1.73 m2; (MDRD). Hypertension was defined to be present if there was a recorded diagnosis of hypertension, systolic blood pressure >130 mmHg and/or diastolic blood pressure >80 mmHg according to ambulatory blood pressure monitoring. None of the hypertensive patients were receiving RAS blockers. Spot urine samples were obtained to measure urinary angiotensinogen (AGT) using human AGT‐ELISA, urinary creatinine and protein levels. The demographic properties and laboratory findings were similar between hypertensive and normotensive transplant recipients. Urinary AGT–creatinine ratio (UAGT/UCre) was significantly higher in hypertensive patients compared with the normotensives (8.98 ± 6.89 μg/g vs. 5.48 ± 3.33 μg/g; P = 0.037). Importantly, a significantly positive correlation was found between UAGT/Ucre levels and proteinuria in hypertensive patients (P = 0.01, r = 0.405). Local intrarenal RAS probably plays an important role in the development of hypertension and proteinuria in renal transplant recipients.

Lansoprazole-induced acute allergic interstitial nephritis in a renal transplant recipient: a case report

Drug-induced interstitial nephritis is one of the causes of graft dysfunction in renal transplant recipients. Although commonly implicated as a cause of drug-induced interstitial nephritis in the general population, proton pump inhibitor-induced interstitial nephritis has not yet been reported in renal transplant recipients. Trimethoprim-sulfamethoxazole is responsible for most cases of interstitial nephritis in this population. Here, we describe the first case of proton pump inhibitor-related interstitial nephritis in a renal transplant recipient.

Right atrial thrombosis complicating renal transplantation in a child

Abstract:  Nephrotic syndrome represents a form of acquired thrombophilia thereby causing increased risk of thrombosis. In patients with nephrotic syndrome both venous and arterial thrombosis can occur; however, intracardiac thrombus is among the rarest reported in the literature. In this case report, we present a 10.5‐yr‐old boy with right atrial thrombosis and an acute rejection episode after renal transplantation due to end stage renal disease caused by focal segmental glomerulosclerosis manifested by nephrotic syndrome. The clinical course was successfully managed with surgical removal of thrombus, institution of anticoagulant as well as antirejection therapy. This report draws attention to the risks that could be associated with thrombosis in renal recipients with congenital or acquired thrombophilias and emphasizes the importance of identifying risk factors for thrombosis in these patients.