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Protective effect of oral l-arginine administration on gentamicin-induced renal failure in rats

We investigated the effects of orally supplemented L-arginine, the substrate of nitric oxide (NO) and N(omega)-nitro-L-arginine methyl ester (L-NAME), a nitric oxide-synthase inhibitor in gentamicin-induced renal failure. Rats were given gentamicin (100 mg/kg/day s.c.), gentamicin and L-arginine (2 g/l, drinking water), gentamicin and L-NAME (100 mg/l, drinking water) or gentamicin plus L-arginine and L-NAME. After 8 days, the gentamicin group developed marked renal failure, characterized by a significantly decreased creatinine clearance and increased blood creatinine, fractional excretion of sodium, fractional excretion of lithium, urine gamma glutamyl transferase, systolic blood pressure and daily urine volume when compared to controls. Renal histological analysis confirmed tubular necrosis. L-arginine administration caused normalization of these parameters, whereas L-NAME led to aggravation of the failure. Concomitant administration of L-NAME and L-arginine to gentamicin-treated rats caused no significant changes when compared to the rats receiving gentamicin alone. We conclude that L-arginine supplementation has beneficial effects in gentamicin-induced renal failure in rats and that these effects are reversed by the NO-synthase inhibitor, L-NAME.

Histologic grading of urothelial papillary neoplasms: impact of combined grading (two-numbered grading system) on reproducibility

The clinical management of tumor patients is often strongly infuenced by the tumor grade. The presence of heterogeneity is well recognized in a variety of tumors. Overall grade is based on highest grade area identified within a tumor. Urothelial carcinoma often contains different histological grades within the same tumor. This study investigates the impact of a combined grading system on the reproducibility of papillary urothelial neoplasms. A set prepared for an earlier study consisting of ten cases of each category (papillary urothelial neoplasm of low malignant potential (PUNLMP), LGPUC, and HGPUC) was used. Agreement between pairs of pathologists was evaluated using κ statistics for the combined scoring system. Interobserver agreement was fair to substantial as reflected by κ values ranging from 0.24 to 0.74 (mean κ = 0.43). The combined scores of 2 and 3 which included PUNLMP showed the lowest degree of agreement and when this category was excluded from the analysis, interobserver agreement increased significantly (mean κ = 0.65; ranging from 0.43 to 0.92) in terms of combined scores of 4, 5, and 6. PUNLMP has been shown to be the least reproducible component of a combined scoring system even among experienced observers. Exclusion of PUNLMP from grading scheme seems to improve interobserver variability.

Recurrent lupus nephritis after transplantation: Clinicopathological evaluation with protocol biopsies.

Lupus nephritis (LN) is an important complication of systemic lupus erythematosus (SLE). The aim is to use indication and protocol biopsies to determine clinicopathological findings and outcomes of patients with LN undergoing kidney transplantation (KTx).

Spectrum of nontumoral renal pathologies in tumor nephrectomies: nontumoral renal parenchyma changes

Non-neoplastic changes are not rarely seen in renal parenchyma of nephrectomy specimens removed for primary renal neoplasms. These changes often involve both kidneys, thus causing impairment of renal function, reducing patients quality of life and sometimes threatening it. Renal tissue accompanying the tumor provides an opportunity in order to evaluate these changes. However, the clinician should make available clinical and laboratory findings involving renal functions of the patient to the pathologist. It is also important that the pathologist must have appropriate knowledge and experience in nephropathology. In this study, we aimed to correlate these changes with the clinical data and make inquiries regarding our experience with nonneoplastic kidney pathology. Consecutive 403 nephrectomy specimens with primary renal neoplasms submitted to our department between 2003 and 2009 were re-examined. Twenty-three nephrectomy materials from 21 patients had non-neoplastic changes, 2 of which were bilateral. Patient follow-up data were obtained from electronic medical records. Of all cases, eight had diabetic nephropathy; 2, amyloidosis; 5, segmental proliferative and/or sclerotic glomerulonephritis; and 6, cystic renal changes. These findings were seen in 5% of nephrectomy specimens diagnosed as clear cell renal cell carcinoma (RCC), chromophobe cell RCC and oncocytoma, whereas this rate was two times higher in nephrectomy specimens with papillary RCC. Most patients with renal failure who were diagnosed with clear cell carcinoma died within the first two years. Despite limited number of cases in our series, prognosis of cases with clear cell RCC were poorer. Consequently, we think that non-neoplastic changes should be reported along with the details regarding the tumor in order to achieve best treatment planning.

Late Conversion From Calcineurin Inhibitor-Based to Sirolimus-Based Immunosuppression Due to Chronic Toxicity : A Prospective Study With Protocol Biopsy Amendment

BACKGROUND There is an emerging consensus on conversion from calcineurin inhibitor (CNI)-based regimens to proliferation signal inhibitor (PSI)-based protocols for the prevention of a progressive decline in graft function due to CNI toxicity. METHODS Thirty-one primary renal transplant recipients within 17-48 years of age (mean, 32.2 +/- 1.6) were enrolled in this dual-center study. Eligible patients had a baseline (pre-engraftment) biopsy and completed at least 12 months of follow-up with deteriorating graft function indicative of chronic CNI toxicity with or without nonspecific interstitial fibrosis/tubular atrophy (IF/TA) on a biopsy specimen. A fast conversion protocol, being defined as a 50% initial reduction followed by complete withdrawal of CNI drug within 2 weeks of introducing rapamycin was performed in all patients. A sirolimus (SRL) loading dose was not prescribed; all subjects directly received maintenance (2-5 mg/d) doses of the drug. The primary endpoint of this study was assessement of renal function using cGFR and renal histology by protocol biopsy at 1 year after conversion. RESULTS The mean follow-up after conversion was 21.6 months. The difference between cGFR before compared with cGFR after 12 months after conversion (40.8 +/- 2.36 mL/min vs 55.7 +/- 3.6 mL/min; P < .000) and at the last follow-up (40.8 +/- 2.36 mL/min vs 53.8 +/- 2.96 mL/min; P < .000) was significant. The mean IF/TA with glomerulosclerosis and chronic vasculopathy scores of biopsy specimens at baseline, during conversion, and at 12 months of the study were 2.25 +/- 0.3, 3.30 +/- 0.24, and 3.0 +/- 0.30, respectively. The change in scores was indicative of mild progression; however, the difference was not significant. IF/TA, glomerulosclerosis, and chronic vasculopathy scores improved in 8 (30%) subjects, remained unchanged in 11 (42%) and worsened in 7 (28%) after 1 year of SRL therapy. After conversion there was no patient or graft loss in this group. Moreover, SCr and GFR improved in 21 or 29 patients (72%), remained stable in 4 (14%), and decreased in 4 (14%) patients. The predictors of successful conversion in our study were GFR > or = 40.6 mL/min, SCr < or = 2.34 mg/dL, and histological allograft damage score < or =3. CONCLUSION SRL-MPA/MMF-ST combination may be a good therapeutic strategy against chronic CNI toxicity, particularly for patients whose conversion biopsy specimens demonstrated mild IF/TA, glomerulosclerosis, and chronic vasculopathy scores (< or =3.1 +/- 0.3).

Testisin karsinoid tümörü: Nadir bir olgu

Noroendokrin tumorler, siklikla gastrointestinal sistem, akciger ve pankreas gibi organlarda gorulmektedir. Primer testikuler noroendokrin tumorler son derece nadir olup, tum testis tumorlerinin %0.23’unu olusturur. 35 yasindaki hasta, sol skrotumda agrisiz sislik sikayeti ile uroloji klinigine basvurdu. Hastada travma hikayesi bulunmamaktaydi. Skrotal Doppler ultrasonograsinde sol testis alt polde 2x1.5 cm boyutlarinda duzgun sinirli solid kitle izlendi. Tumor markerlari ve bilgisayar tomografi taramalari normaldi ve hastada metastaz izlenmedi. Hastaya sol radikal orsiektomi uygulandi. Orsiektomi materyali, makroskobik olarak 1.4x1.2 cm boyutlarda duzgun sinirli, sari solid kitle olarak izlendi. Histopatolojik incelemede primer testikuler karsinoid tumor, iyi diferansiye noroendokrin karsinomdan ayirt edilemedi. Primer testikuler karsinoid tumor tanisi, klinik ve radyolojik olarak ekstratestikuler noroendokrin tumor dislanarak yapildi. Bu nadir olgu, morfolojik ve immunhistokimyasal ozellikleri ile sunulmustur.

Granulomas in clear cell renal cell carcinomas

Aim: In this study our goal is to investigate the incidence, causes and relationship with the prognostic parameters of granulomatous reaction in clear cell renal cell carcinomas. Materials and Methods: The frequency of granulomatous reaction was analyzed in 389 renal cell carcinoma specimens from 5 different centers. The cause of granulomatous reaction, relationship between granulomatous reaction and pathologic prognostic parameters were analyzed. Results: Granulomatous reaction was observed in 11 of the 389 patients. Granulomas were localized in the tumor stroma without necrosis. There was no significant correlation between the presence of granulomatous reaction and the other prognostic factors like age, gender, tumor size, tumor stage and Fuhrman degree. Conclusion: The presence of granulomatous reaction in the tumor stroma in clear cell renal cell carcinomas in nephrectomy specimens is rare. In this small series, the presence of granulomas in clear cell renal cell carcinoma seems not to be related with prognosis.

To what extent estimated or measured GFR could predict subclinical graft fibrosis: a comparative prospective study with protocol biopsies

Monitoring of allograft function entails methods more accurate than serum creatinine and creatinine‐based GFR equations (eGFR). This prospective trial aimed at investigating the diagnostic accuracy of creatinine‐ and cystatin C‐based eGFR with measured GFR (mGFR) and compared them with graft fibrosis detected by protocol biopsies (PBx). Forty‐four kidney transplant recipients were enrolled. PBx were obtained postengraftment and at 6th and 12th months. GFR was measured by Tc‐99m DTPA at 3th, 6th, and 12th months after transplantation. Significant correlation existed between eGFR and mGFR at 3, 6, and 12 months (P < 0.0001). Cystatin C‐based Hoek and Larsson equations had the lowest bias and highest accuracy. The sum of interstitial fibrosis and tubular atrophy score increased from implantation to 6th and 12th months (0.52 ± 0.79, 0.84 ± 0.88, 1.50 ± 1.35). This was accompanied by reduction of mGFR from 54.1 ± 15.2 to 49.9 ± 15.2 and 46.8 ± 16.5 ml/min/1.73 m2, while serum creatinine, cystatin C, and eGFR remained stable. Neither creatinine‐ nor cystatin C‐based GFR equations are reliable for detecting insidious graft fibrosis. In the first year after transplantation, mGFR, with its best proximity to histopathology, can be used to monitor allograft function and insidious graft fibrosis.