Effect of octreotide on oxidative stress in the erythrocyte and kidney tissue in adriamycin-induced experimental nephrotic syndrome model / Efeito do octreotide no estresse oxidativo em eritrócitos e no tecido renal no modelo de síndrome nefrótica experimental induzida por adriamicina

Abstract Introduction: Nephrotic syndrome (NS) is one of the reasons of end-stage kidney disease, and elucidating the pathogenesis and offer new treatment options is important. Oxidative stress might trigger pathogenesis systemically or isolated in the kidneys. Octreotide (OCT) has beneficial antioxidant effects. We aimed to investigate the source of oxidative stress and the effect of OCT on experimental NS model. Methods: Twenty-four non-uremic Wistar albino rats were divided into 3 groups. Control group, 2 mL saline intramuscular (im); NS group, adriamycin 5 mg/kg intravenous (iv); NS treatment group, adriamycin 5 mg/kg (iv) and OCT 200 mcg/kg (im) were administered at baseline (Day 0). At the end of 21 days, creatinine and protein levels were measured in 24-hour urine samples. Erythrocyte and renal catalase (CAT) and thiobarbituric acid reactive substance (TBARS) were measured. Renal histology was also evaluated. Results: There was no significant difference among the 3 groups in terms of CAT and TBARS in erythrocytes. Renal CAT level was lowest in NS group, and significantly lower than the control group. In treatment group, CAT level significantly increased compared with NS group. In terms of renal histology, tubular and interstitial evaluations were similar in all groups. Glomerular score was significantly higher in NS group compared with control group and it was significantly decreased in treatment group compared to NS group. Conclusions: Oxidative stress in NS might be due to the decrease in antioxidant protection mechanism in kidney. Octreotide improves antioxidant levels and histology in renal tissue and might be a treatment option.

Resumo Introdução: Síndrome nefrótica (SN) é uma das causas de doença renal em estágio terminal. É importante elucidar a patogênese e oferecer novas opções de tratamento. Estresse oxidativo pode desencadear a patogênese sistemicamente ou isoladamente nos rins. O octreotide (OCT) tem efeitos antioxidantes benéficos. Nosso objetivo foi investigar a fonte de estresse oxidativo e efeito do OCT no modelo experimental de SN. Métodos: Dividimos 24 ratos albinos Wistar não urêmicos em 3 grupos. Grupo controle, 2 mL de solução salina intramuscular (im); grupo SN, adriamicina 5 mg/kg intravenosa (iv); grupo tratamento SN, adriamicina 5 mg/kg (iv) e OCT 200 mcg/kg (im) foram administrados no início do estudo (Dia 0). Aos 21 dias, mediram-se os níveis de creatinina e proteína em amostras de urina de 24 horas. Mediu-se a catalase (CAT) eritrocitária e renal e a substância reativa ao ácido tiobarbitúrico (TBARS). Avaliou-se também histologia renal. Resultados: Não houve diferença significativa entre os três grupos em termos de CAT e TBARS em eritrócitos. O nível de CAT renal foi menor no grupo SN e significativamente menor que no grupo controle. No grupo tratamento, o nível de CAT aumentou significativamente em comparação com o grupo SN. Quanto à histologia renal, as avaliações tubular e intersticial foram semelhantes em todos os grupos. O escore glomerular foi significativamente maior no grupo SN em comparação com o grupo controle e diminuiu significativamente no grupo de tratamento em comparação com o grupo SN. Conclusões: Estresse oxidativo na SN pode ser devido à diminuição do mecanismo de proteção antioxidante nos rins. O octreotide melhora níveis de antioxidantes e histologia do tecido renal e pode ser uma opção de tratamento.

Effect of octreotide on oxidative stress in the erythrocyte and kidney tissue in adriamycin-induced experimental nephrotic syndrome model.

INTRODUCTION: Nephrotic syndrome (NS) is one of the reasons of end-stage kidney disease, and elucidating the pathogenesis and offer new treatment options is important. Oxidative stress might trigger pathogenesis systemically or isolated in the kidneys. Octreotide (OCT) has beneficial antioxidant effects. We aimed to investigate the source of oxidative stress and the effect of OCT on experimental NS model. METHODS: Twenty-four non-uremic Wistar albino rats were divided into 3 groups. Control group, 2 mL saline intramuscular (im); NS group, adriamycin 5 mg/kg intravenous (iv); NS treatment group, adriamycin 5 mg/kg (iv) and OCT 200 mcg/kg (im) were administered at baseline (Day 0). At the end of 21 days, creatinine and protein levels were measured in 24-hour urine samples. Erythrocyte and renal catalase (CAT) and thiobarbituric acid reactive substance (TBARS) were measured. Renal histology was also evaluated. RESULTS: There was no significant difference among the 3 groups in terms of CAT and TBARS in erythrocytes. Renal CAT level was lowest in NS group, and significantly lower than the control group. In treatment group, CAT level significantly increased compared with NS group. In terms of renal histology, tubular and interstitial evaluations were similar in all groups. Glomerular score was significantly higher in NS group compared with control group and it was significantly decreased in treatment group compared to NS group. CONCLUSIONS: Oxidative stress in NS might be due to the decrease in antioxidant protection mechanism in kidney. Octreotide improves antioxidant levels and histology in renal tissue and might be a treatment option.

A rare cause of AA amyloidosis: Glomus tumor and treatment with anakinra-Case report and literature review.

Systemic AA amyloidosis is associated with poorly controlled chronic inflammatory disorders. Chronic infections and inflammatory arthritis are the most common causes; however, they can also rarely occur as a complication of neoplastic disorders. The development of AA amyloidosis secondary to paraganglioma, which is a rare type of tumor, has rarely been reported in the literature. In this case, an 85-year-old female patient with a glomus tumor in the neck, who has been followed up over 50 years, applied with complaints of loss of appetite, nausea, and diarrhea for 5-6 months. While evaluating the patient, who had high levels of acute phase reactants, amyloidosis was diagnosed by salivary gland biopsy. No other cause was found to explain amyloidosis. The patient, who could not tolerate treatment with colchicine and azathioprine, is successfully treated with the interleukin-1 inhibitor anakinra. A rare relationship, systemic AA amyloidosis, which is thought to have developed as a result of long-standing jugular paraganglioma, is presented in this article. In addition, publications showing an association between paragangliomas and amyloidosis were reviewed.

Coexistence of Sjögren's syndrome and pulmonary nodular amyloidosis.

There are very few cases in the literature on the coexistence of Sjögren's syndrome and pulmonary nodular amyloidosis being treated with rituximab. When nodules with central calcification and cystic lesions are seen on computed tomography, amyloid lung should be considered. Biopsy is recommended as it can be confused with malignancies. In this article, we present a 66-year-old female patient who has been followed up for Sjögren's syndrome for 26 years. Multiple cystic lesions with central calcification in the lung were detected and it was evaluated as amyloid nodule in the biopsy performed. The patient is being followed and is stable under rituximab treatment. Pulmonary noduler amyloidosis is very rare in Sjögren patients and there are very few cases where rituximab is used for treatment. We decided to publish in order to guide clinicians who will encounter similar cases.

C4d as a Practical Marker for Cutaneous Amyloidosis.

ABSTRACT: Cutaneous amyloidosis (CA) is defined by the accumulation of amyloid in the dermis; it might be primary or secondary. The diagnosis is based on histopathological findings with the demonstration of amyloid deposits, confirmed by Congo red stain under the polarized light. Studies on other diagnostic markers are ongoing in the literature. The aim of this study was to demonstrate the utility of C4d staining in the recognition of amyloid in CA and using it as an alternative or substitute marker for the diagnosis. In this retrospective study, 199 skin biopsies with a clinical provisional diagnosis of CA were analyzed, the Congo red stain was performed, and, in a subgroup (n = 97) with histopathological findings probably for CA, C4d immunohistochemistry was assessed. Forty-eight cases of CA were detected. Congo red birefringence was positive in all cases, whereas in 14 cases, it was faded. In these 14 cases, the diagnosis of CA was made by means of Congo red fluorescence and Thioflavin T because the histopathological findings were highly suggestive for CA. All CA cases were positive with C4d, and in 12 of the 49 inflammatory dermatoses, C4d was positive. The interpretation of C4d immunohistochemistry can be performed more easily and rapidly than Congo red evaluation. The sensitivity and specificity of C4d were 100% and 75.5%, respectively. In our experience, C4d staining was a useful method for detecting amyloid deposits in CA. Although Congo red staining is the gold standard for amyloid detection, we propose C4d immunohistochemistry as a routine screening method or hybrid transition while further investigations are completed.

A histopathological scoring and grading system to predict outcome for patients with AA amyloidosis.

PURPOSE: Renal involvement is associated with significant morbidity and mortality in AA amyloidosis. Extend of amyloid deposition in kidney biopsies may be predictive for clinical manifestations and outcomes. The aim of our study is to assess clinical features of patients with biopsy-proven renal AA amyloidosis and to evaluate the relationship between histopathological scoring and grading of renal amyloid deposition with clinical findings and outcomes. METHODS: The study included 86 patients who were diagnosed with renal AA amyloidosis. The demographic and clinical features at the time of biopsy and follow-up data were retrospectively collected. Amyloid deposition in glomeruli, interstitium, vessels and tubulointerstitial findings were scored and renal amyloid prognostic score (RAPS) was assigned by adding all scores. RAPS was further divided into three grades (RAPS grade I, II, III). RESULTS: Median age was 50 (36-59) years. Familial Mediterranean fever was the leading cause. RAPS grade and interstitial inflammatory infiltration were associated with baseline eGFR and glomerular amyloid deposition was associated with proteinuria. During the follow-up period (median 50 months), 39 patients developed ESRD. Extensive (involving > 50%) glomerular amyloid deposition, baseline eGFR and proteinuria were independent risk factors for progression to end stage renal disease. Death censored renal survival was significantly lower among patients with RAPS grade III compared to those with RAPS grade I and II. Patient survival rate was not different according to RAPS grade. CONCLUSIONS: Degree of renal amyloid accumulation is associated with renal function and outcome. The scoring and grading system may be predictive in clinical outcome and contribute to understanding of disease mechanism.

Acoustic Radiation Force Impulse Elastography May Predict Acute Rejection in Kidney Transplantation.

BACKGROUND: Allograft biopsy that is done as indicated by clinical and laboratory clues about graft rejection provides a definitive diagnosis. Noninvasive methods that may be useful for predicting or diagnosing rejection are important for early diagnosis of possible rejection. PURPOSE: The aim of this study is to investigate the relationship between changes in shear wave velocity (SWV) values and renal allograft kidney biopsy findings. MATERIAL AND METHODS: Thirty-four end-stage renal failure patients who underwent living donor renal transplantation between January 2015 and July 2015 were enrolled in this prospective cohort study. Implantation, sixth-month protocol, and biopsies that were performed with suspicion of acute rejection were evaluated with renal Doppler ultrasound and elastography findings of recipients' preimplantation donor ultrasonography findings. RESULTS: Comparison of renal ultrasound and elastography findings of 2 groups revealed a significant elevation in the resistive index (0.81 vs 0.63, P = .005) and pulsatility index (2.08 vs 1.20, P = .008) values in the rejection group, and no significant difference in the SWV values between the 2 groups. Delta (Δ)-SWV was calculated using the difference between acute rejection values and preimplantation, implantation, and sixth-month values showed a positive correlation between acute rejection (Δ-sixth month, r = 0.498, P = .030), tubulitis (Δ-pretransplant, r = 0.509, P = .037), and inflammation (Δ-pretransplant, r = 0.657, P = .004) scores. However, there were no correlations between Δ-SWV values and glomerulitis and peritubular capillaritis score. CONCLUSION: Changes in SWV may predict acute rejection in kidney transplantation patients if the reference measurements were done at a more stable time after the transplantation.

Increase in interventricular septum thickness may be the first sign of cardiovascular change in kidney donors.

BACKGROUND: Because of the inadequate number of deceased kidney donors, living kidney donation remains an important issue for kidney transplantation. Previous studies have shown that living donation does not differ life expectancy and progression to end-stage renal disease compared with the normal population. In this study, we investigated short-term cardiovascular changes after donor nephrectomy. METHODS: Thirty-four patients who underwent donor nephrectomy between January 2015 and July 2015 at Ege University Renal Transplantation Unit were included in the study. Arterial stiffness, multifrequency bioimpedance analysis, renal ARFI elastography, and echocardiography performed prior to the donor nephrectomy and 6 months after nephrectomy. RESULTS: A total of 34 kidney donors were enrolled in this study. Twenty donors were female (59%) and 14 donors were male (41%). The pathological evaluation of donor kidneys using implantation renal biopsy sample revealed mean Karpinski Renal Score of 1.5 and the mean glomerulosclerosis ratio was 5% for all donated kidneys. Arterial stiffness, systolic and diastolic blood pressure measures, body fluid composition, and left atrial size did not change significantly during the follow-up. However, interventricular septum thickness of donors increased by 1 mm during a 6-month period (9.6 mm vs 10.6 mm, P = .002). CONCLUSION: We observed an increase in interventricular septum thickness in kidney donors during a 6-month follow-up. In order to evaluate the net effect of this change on donor morbidity, prospective studies investigating an increased number of donors with long-term follow-up should be needed.

Membranous nephropathy in a child with crescentic glomerulonephritis: Coincidence or comorbidity?

Rapidly progressive glomerulonephritis (RPGN) is rare syndrome in children, characterized by clinical features of glomerulonephritis and rapid loss of renal function, and is associated with crescentic glomerulonephritis. Primary membranous nephropathy (MN) is an immune-complex-mediated cause of the adult nephrotic syndrome but occurs less frequently in children. RPGN is rarely observed in adults with primary MN. In this article, we report a case of MN, which developed during long-term follow-up of previously treated RPGN. Our case may be the first to demonstrate primary MN and crescentic glomerulonephritis in a child. We would like to underline the importance of not dropping the long-term follow-up of cases with primary RPGN (not accompanied by other glomerulonephritis and vasculitis symptoms) who had improved with treatment.

Investigation of the Factors Affecting Allograft Kidney Functions: Results of 10 Years.

INTRODUCTION: Significant improvements in patient and graft survival and reductions in the frequency of acute rejection were obtained in the early period after renal transplantation, but this success was not sufficiently reflected in the long term. Allograft kidney losses in the long term remain a significant problem. In this study, we investigated the specific causes of graft losses in patients who had a good clinical course in the first year but developed graft loss in the long term. METHODS: A total of 118 patients who underwent kidney transplantation in 2005 and 2006 in the Organ Transplantation Center of Ege University Medical Faculty Hospital were evaluated. The inclusion criteria were to be older than 18 years and have a serum creatinine value of <2 mg/dL at the 12th month after transplantation. RESULTS: Sixty-one percent of the recipients were male, and the mean age at the time of transplantation was 34 ± 11 years (18 to 61). We observed 29 graft losses during the mean follow-up period of 129 ± 35 months (27 to 162). Three of the graft losses were death by functional graft. Of the 26 patients with graft loss, 16 had chronic rejection, and 8 had recurrent glomerulonephritis. The relationship between nonimmune causes and graft loss was not detected. CONCLUSIONS: In conclusion, nonimmune factors may not be as important as we think in relatively young and healthier recipients. Chronic rejection and recurrent glomerulonephritis are the main causes of long-term graft loss of patients with good graft function at the end of the first year. Improvement of long-term survival will be possible with the prevention and effective treatment of these 2 problems.

Do Antithymocyte Globulin-Free Acute Rejection Therapies Increase the Risk of Polyoma Nephropathy in Renal Transplant Recipients?

INTRODUCTION: BK virus nephropathy is a serious complication that can lead to allograft kidney loss. Excessive immunosuppression increases the risk. We aimed to evaluate whether there is an increased risk of BK viremia and nephropathy in patients who underwent high-dose immunosuppression because of the development of acute rejection in the early period after kidney transplantation. METHODS: This retrospective cohort study was performed between April 2015 and March 2016. Twenty-nine patients who had biopsy-proven acute rejection in the first 3 months were evaluated for BK viremia and nephropathy. Thirty patients who had transplantations at the same period were the control group. Plasma BK-DNA values were examined at 1, 2, 3, 6, 9, and 12 months after the rejection treatment and at 3, 6, 9, and 12 months in the control group. Presence of polyoma nephropathy was examined with surveillance biopsies at the 6 and 12 months. RESULTS: Acute rejection treatment was started on the 12th day after transplantation (2-37 days). Seventeen cellular rejections and 12 humoral rejections were reported by biopsy. Two of the 12 humoral rejections were suspicious. Only pulse steroid (PS) (n = 18); PS, plasmapheresis, and intravenous immunoglobulin (n = 8); PS and intravenous immunoglobulin (n = 2); and PS and plasmapheresis (n = 1) treatments were performed. In 21 patients in the rejection group and 25 patients in the control group, BK-DNA was not positive at all. Two patients had graft loss at 11 and 36 months in the rejection group. Graft losses were secondary to rejection. CONCLUSIONS: Treatment with antithymocyte globulin-free regimens after acute rejection episodes did not lead to an increase in BK viremia.

Gemcitabine hydrochloride microspheres used for intravesical treatment of superficial bladder cancer: a comprehensive in vitro/ex vivo/in vivo evaluation.

INTRODUCTION: Bladder cancer is responsible for more than 130,000 deaths annually worldwide. Intravesical delivery of chemotherapeutic agents provides effective drug localization to the target area to reduce toxicity and increase efficacy. This study aimed to develop an intravesical delivery system of gemcitabine HCl (Gem-HCl) to provide a sustained-release profile, to prolong residence time, and to enhance its efficiency in the treatment of bladder cancer. MATERIALS AND METHODS: For this purpose, bioadhesive microspheres were successfully prepared with average particle size, encapsulation efficiency, and loading capacity of 98.4 µm, 82.657%±5.817%, and 12.501±0.881 mg, respectively. For intravesical administration, bioadhesive microspheres were dispersed in mucoadhesive chitosan or in situ poloxamer gels and characterized in terms of gelation temperature, viscosity, mechanical, syringeability, and bioadhesive and rheological properties. The cytotoxic effects of Gem-HCl solution, Gem-HCl microspheres, and Gem-HCl microsphere-loaded gel formulations were evaluated in two different bladder cancer cell lines: T24 (ATCC HTB4TM) and RT4 (ATCC HTB2TM). RESULTS: According to cell-culture studies, Gem-HCl microsphere-loaded poloxamer gel was more cytotoxic than Gem-HCl microsphere-loaded chitosan gel. Antitumor efficacy of newly developed formulations were investigated by in vivo studies using bladder-tumor-induced rats. CONCLUSION: According to in vivo studies, Gem-HCl microsphere-loaded poloxamer gel was found to be an effective and promising alternative for current intravesical delivery-system therapies.

A new type of familial partial lipodystrophy: distinctive fat distribution and proteinuria.

PURPOSE: To describe an interesting subtype of familial partial lipodystrophy (FPLD). METHODS: The phenotype of this distinctive FPLD subtype was studied in three Turkish female siblings. RESULTS: Mutation testing was negative for the genes associated with lipodystrophy syndromes. In MRI studies, fat loss was prominent in the posterior aspects of the proximal lower limbs, whilst some fat was preserved in the anterior, medial and lateral aspects. Remarkably, fat tissue was preserved in the distal part of the limbs. Local fat accumulation was observed in the mons pubis area. Asymmetrical fat loss was also remarkable in the upper extremities. All three patients had severe insulin resistance associated with diabetes mellitus, acanthosis nigricans, hypertriglyceridemia and hepatic steatosis. Abnormal amounts of proteinuria were detected in all three subjects. Renal biopsy showed mild tubular atrophy, interstitial fibrosis, irregular thickening and wrinkling of glomerular basal membranes, small areas of segmental sclerosis and pedicel effacement. CONCLUSIONS: We reported a form of FPLD characterized by a striking pattern of highly selective partial fat loss and proteinuria.

Renal complications of lipodystrophy: A closer look at the natural history of kidney disease.

OBJECTIVES: Lipodystrophy syndromes are a group of heterogeneous disorders characterized by adipose tissue loss. Proteinuria is a remarkable finding in previous reports. STUDY DESIGN: In this multicentre study, prospective follow-up data were collected from 103 subjects with non-HIV-associated lipodystrophy registered in the Turkish Lipodystrophy Study Group database to study renal complications in treatment naïve patients with lipodystrophy. METHODS: Main outcome measures included ascertainment of chronic kidney disease (CKD) by studying the level of proteinuria and the estimated glomerular filtration rate (eGFR). Kidney volume was measured. Percutaneous renal biopsies were performed in 9 patients. RESULTS: Seventeen of 37 patients with generalized and 29 of 66 patients with partial lipodystrophy had CKD characterized by proteinuria, of those 12 progressed to renal failure subsequently. The onset of renal complications was significantly earlier in patients with generalized lipodystrophy. Patients with CKD were older and more insulin resistant and had worse metabolic control. Increased kidney volume was associated with poor metabolic control and suppressed leptin levels. Renal biopsies revealed thickening of glomerular basal membranes, mesangial matrix abnormalities, podocyte injury, focal segmental sclerosis, ischaemic changes and tubular abnormalities at various levels. Lipid vacuoles were visualized in electron microscopy images. CONCLUSIONS: CKD is conspicuously frequent in patients with lipodystrophy which has an early onset. Renal involvement appears multifactorial. While poorly controlled diabetes caused by severe insulin resistance may drive the disease in some cases, inherent underlying genetic defects may also lead to cell autonomous mechanisms contributory to the pathogenesis of kidney disease.

Scintigraphic and Sonographic Findings of Subcapsular Cortical Necrosis in a Transplanted Kidney.

Renal transplant scintigraphy, performed in a 23-year-old man who had renal graft from a living donor, showed nearly normal perfusion and moderately low function of the graft. But the margins of the graft were blurred, and it was interestingly appearing enlarged late in the study. Ultrasound demonstrated a hypoechoic rim surrounding the whole kidney. Biopsy revealed necrosis besides normal cortical tissue. Necrosis was thought to be limited to the subcapsular cortical area. It should be considered that these scintigraphic findings could be due to greatly reduced and delayed perfusion of edematous subcapsular necrotic area of the graft even in normal perfusion images.

Persistent Müllerian Duct Syndrome with Transverse Testicular Ectopia: A Novel Anti-Müllerian Hormone Receptor Mutation.

Persistent Müllerian duct syndrome is the result of either anti-Müllerian hormone (AMH) deficiency or AMH receptor resistance. A long tubular structure was palpated during the physical examination of a 13-month-old male patient who had presented with bilateral undescended testes. At physical examination, the testes were not palpable. The patient's karyotype was XY, SRY (+), and his AMH level was 22 ng/mol. Structures suggestive of ovaries, a uterus, and fallopian tubes were observed during the laparoscopic examination of the ectopic testis. AMHR2 gene sequence analysis performed with a preliminary diagnosis of AMH receptor resistance revealed a previously unreported homozygous c.24G>A (p.W8X) mutation. The patient was assessed as a case of AMH receptor resistance. Orchiopexy was performed.

Acinar Adenocarcinoma of Prostate with Predominant Ttf-1 Positive Intraductal Component.

Intraductal carcinoma of prostate has been previously described in radical prostatectomies. It's rarely encountered in needle biopsies in the absence of infiltrative carcinoma. But, both histogenesis and nomenclature of the lesion is still controversial. Among the pure intraductal carcinoma of prostate cases, a different solid patern was described with smaller nuclei at the center of the ducts. However, there is a lack of information about the association of those cases with acinar prostate adenocarcinoma. Herein, we describe a case of acinar adenocarcinoma with predominant non-neuroendocrine TTF-1 positive small cell intraductal component.

The effect of hypercalcemia on allograft calcification after kidney transplantation.

PURPOSE: Persistent hypercalcemia after kidney transplantation (KTx) may cause nephrocalcinosis and graft dysfunction. The aim of this study was to evaluate patients with hypercalcemia and assess its effect on tubulointerstitial calcification. METHODS: A total of 247 recipients were enrolled. Transient and persistent hypercalcemia was defined as hypercalcemia (corrected serum calcium >10.2 mg/dL) persisting for 6 and 12 months after KTx, respectively. The severity of calcification in the 0-h, 6- and 12-month protocol biopsies of patients with transient (n = 8) and persistent hypercalcemia (n = 20) was compared with a matched control group (n = 28). RESULTS: Twenty-eight patients were hypercalcemic at 6 months posttransplantation. Serum calcium levels were normalized in eight of them at the end of the first year. Dialysis duration was a positive predictor of persistent hypercalcemia. Tubulointerstitial calcification was detected in 70.6 and 90 % of patients with persistent hypercalcemia at 6 and 12 months posttransplantation, respectively. In 20 % of patients with transient hypercalcemia, severity of calcification regressed at 12 months posttransplantation along with normalization of serum calcium levels. Graft functions and histopathological findings (ci, ct, ci + ct, cv, ah, percentage of sclerotic glomeruli) were not different at 6 and 12 months posttransplantation. CONCLUSIONS: Hypercalcemia and persistent hyperparathyroidism are not rare after KTx. Tubulointerstitial calcification is more common and progressive among patients with persistent hypercalcemia. Normalization of calcium levels may contribute to regression of calcification in some patients.

P21 and p27 Immunoexpression in Upper Urinary Tract Urothelial Carcinomas.

p21 and p27 are members of cyclin-dependent kinase family, which function as tumor suppressors and they are involved in development and progression of several malignancies. We investigated their expression in upper urinary tract urothelial carcinoma (UUTUC). Radical nephroureterectomy materials of 34 patients were assessed by immunohistochemistry to evaluate expression of p21 and p27 in UUTUC. Results were correlated with various clinicopathological variables as age, gender, tumor grade and stage, tumor architecture, multifocality, subsequent bladder carcinoma development and clinical outcome.p21 and p27 expression was observed in 52.9 % (n = 18) and 88.2 % (n = 30), respectively. A total of 21 tumors (61.7 %) showed either total loss of p21 expression (n = 16, 47 %) or lower expression (n = 5, 14.7 %). No correlation was found between p21 expression and clinicopathologic variables. Cases showing total loss or lower p27 expression (11.7 % and <25.6 %, respectively) (n = 19, 55.8 %) constituted 67.6 % (n = 23) of the cases totally. This loss or lower p27 expression correlated with a shorter overall survival in both univariate and multivariate analysis (p = 0.039 and p = 0.037, respectively). None of the noninvasive tumors (papillary and nodular tumors) showed loss of p27 (p = 0.016) while 33.3 % of invasive ones showed p27 loss. Noninvasive tumor architecture also correlated with subsequent bladder carcinoma development (p = 0.032) while invasive tumor architecture correlated with advanced stage (T3 and T4) (p = 0.003). p27 is widely expressed in UUTUC, while p21 expression is observed in half of the cases. Loss of p27 expression correlated with tumor architecture and overall survival in UUTUC. However, further research is needed to assess their role in UUTUC.