Renal Cell Carcinoma in End-Stage Renal Disease: A Retrospective Study in Patients from Hungary.

INTRODUCTION: End-stage renal disease (ESRD) and acquired cystic kidney disease (ACKD) are known risk factors for renal cell carcinoma (RCC). Hereby, the clinicopathological features of RCCs developed in ESRD were investigated. METHODS: A database consisting of 34 tumors from 31 patients with ESRD among 2,566 nephrectomy samples of RCC was built. The demographic, clinical, and follow-up data along with pathological parameters were analyzed. The RCCs were diagnosed according to the current WHO Classification of Urinary and Male Genital Tumors. RESULTS: Twenty-two tumors developed in men and 12 in women, with a median age of 56 years (range: 27-75 years). The causes of ESRD were glomerulonephritis (n = 7), hypertensive kidney disease (n = 6), autosomal dominant polycystic kidney disease (n = 6), chronic pyelonephritis (n = 4), diabetic nephropathy (n = 3), chemotherapy-induced nephropathy (n = 1), and undetermined (n = 4). ACKD complicated ESRD in 12 patients. The following histological subtypes were identified: clear cell RCC (n = 19), papillary RCC (n = 5), clear cell papillary tumor (n = 5), ACKD RCC (n = 3), and eosinophilic solid and cystic RCC (n = 2). The median tumor size was 31 mm (range: 10-80 mm), and 32 tumors were confined to the kidney (pT1-pT2). There was no tumor-specific death during the period of this study. Progression was registered in 1 patient. CONCLUSION: In our cohort, the most common RCC subtype was clear cell RCC (55%), with a frequency that exceeded international data appreciably (14-25%). The incidence of clear cell papillary tumor and ACKD RCC (14.7% and 8.5%) was lower than data reported in the literature (30% and 40%). Our results indicate a favorable prognosis of RCC in ESRD.

A systematic analysis of the complement pathways in patients with neuromyelitis optica indicates alteration but no activation during remission.

Neuromyelitis optica (NMO) is an autoimmune demyelinating inflammatory disorder, mediated by pathogenic autoantibodies against aquaporin 4 (AQP4), the main water channel of the central nervous system (CNS). NMO is characterized by local IgG deposition and complement activation within the CNS, but the three complement pathways have not been systematically investigated. We evaluated the overall activation of the classical, alternative, and MBL-lectin pathways in the peripheral blood of 25 patients with AQP4-seropositive NMO spectrum during remission and 113 healthy controls by three ways: (1) we measured the concentrations of native complement proteins of the three pathways [C1-inhibitor (C1-inh), C1q, C4, C3, C5, factor I, factor B, properdin]; (2) the concentrations of complement products suggesting in vivo activation (C1rC1sC1-inh, C3a, C3bBbP, and SC5b-9); and (3) the total activity of the three complement pathways. Additionally we measured levels of C1rC1sC1-inh, C3a, C3bBbP in cerebrospinal fluid (CSF) of 6 patients with relapsing NMO and of 18 patients with relapsing multiple sclerosis (MS). The serological studies indicated that total complement activity of the classical [median (interquartile range) 72 (61-82) vs. 65 (56-73) CH50/mL; p=0.0122] and of the lectin pathways [73 (59-111) vs. 49 (3-92)%; p=0.0078)] were elevated compared with the controls, whereas that of the alternative pathway was not significantly different. The levels of C3 [1.1 (0.9-1.3) vs. 1.4 (1.2-1.5)g/L; p<0.0001], factor B [89 (77-115) vs. 103 (93-113)%; p=0.0397] and factor I [85 (69-95) vs. 101 (93-107)%; p=0.0007], as well as of properdin [92 (74-104) vs. 108 (97-122)%; p=0.0028] were significantly lower in the patients than in the controls. The only increase in the patients was ascertained in the relative concentration of C1rC1sC1-inh vs. the C1-inhibitor (42.3 [31.9-65.0] vs. 30.8 [13.5-43.5] AU/mg; p=0.0007). The absolute and relative levels of the other complement activation products were not elevated in the patients. On the contrary, the serum concentrations of C3a, C3bBbP, and SC5b-9 of the patients were lower than those of the controls. The absolute concentration of the complement activation products (C1rC1sC1-inh, C3bBbP, C3a) and the ratio of C3bBbP/C1rC1sC1-inh did not differ in NMO and MS CSF samples. The ratio of C3bBbP/C1rC1sC1-inh was similar in NMO plasma and CSF samples. We found a higher ratio of C3bBbP/C1rC1sC1-inh in the plasma of control subjects compared to those in any pathological samples. Our results do not indicate substantial systemic complement activation if NMO activity is adequately controlled; nevertheless, the complement system is abnormally affected even during remission. The relative ancillarity of the alternative compared to the classical pathway may also suggest that suppression of the alternative pathway by treatment may be important to achieve remission.