Regular use of analgesics is a risk factor for renal cell carcinoma

Phenacetin-based analgesics have been linked to the development of renal pelvis cancer and renal cell carcinoma (RCC). The relationship between non-phenacetin types of analgesics and kidney cancer is less clear, although laboratory evidence suggests that these drugs possess carcinogenic potential. A population-based case–control study involving 1204 non-Asian RCC patients aged 25–74 and an equal number of sex-, age- and race-matched neighbourhood controls was conducted in Los Angeles, California, to investigate the relationship between sustained use of analgesics and risk of RCC according to major formulation categories. Detailed information on medical and medication histories, and other lifestyle factors was collected through in-person interviews. Regular use of analgesics was a significant risk factor for RCC in both men and women (odds ratio (OR) = 1.6, 95% confidence interval (CI) = 1.4–1.9 for both sexes combined). Risks were elevated across all four major classes of analgesics (aspirin, non-steroidal anti-inflammatory agents other than aspirin, acetaminophen and phenacetin). Within each class of analgesics, there was statistically significant increasing risk with increasing level of exposure. Although there was some minor variability by major class of formulation, in general individuals in the highest exposure categories exhibited approximately 2.5-fold increase in risk relative to non- or irregular users of analgesics. Subjects who took one regular-strength (i.e. 325 mg) aspirin a day or less for cardiovascular disease prevention were not at an increased risk of RCC (OR = 0.9, 95% CI = 0.6–1.4). © 1999 Cancer Research Campaig

Renal impairment in deoxycorticosterone acetate-salt hypertensive rats

This study has compared renal function in deoxycorticosterone (DOCA)-salt hypertensive Wistar rats (uninephrectomy followed by administration of DOCA 25 mg subcutaneously every fourth day and 1% NaCl in the drinking water) with various control rats using the isolated perfused kidney preparation. The systolic blood pressure of DOCA-salt hypertensive rats was 180 +/- 10 mmHg (uninephrectomy controls: 136 +/- 9 mmHg) while normalization of calcium intake (DOCA-Ca rats, 1% CaCl2 in water) attenuated this increase (systolic blood pressure, 146 +/- 5 mmHg). Renal mass corrected for body weight increased by 25% after uninephrectomy, 55% in uninephrectomized rats given NaCl, 152% in DOCA-salt rats and 147% in DOCA-Ca rats. At a renal perfusion pressure of 135 mmHg, isolated perfused kidneys from DOCA-salt rats showed decreases of 48% in glomerular filtration rate and 69% in sodium excretion with an increase of 44% in renal vascular resistance compared with uninephrectomized rats. There were no significant differences in renal function between DOCA-salt and DOCA-Ca rats. Histological assessment of renal pathology showed proximal tubular hypertrophy and hyperplasia, marked focal distal tubular atrophy, interstitial fibrosis and glomerular hypercellularity in DOCA rats compared with UNX rats. Lesions were less obvious in UNX-salt or DOCA-Ca rats. The lack of direct correlation between alterations in function and pathology may be explained by the compensatory effect of remaining healthy or hypertrophied nephrons. Thus, the DOCA-salt model of hypertension in rats is associated with marked structural kidney damage and severely decreased kidney function. Marked attenuation of systemic hypertension by normalizing calcium intake in DOCA-salt rats did not prevent impairment of kidney function

Effect of CD40 and sCD40L on renal function and survival in patients with renal artery stenosis

Activation of the CD40 receptor on the proximal tubular epithelium of the kidney results in fibrosis and inflammation in experimental models of kidney injury. Soluble CD40 ligand is released by activated platelets. The role of CD40-soluble CD40 ligand in patients with ischemic renal disease is unknown. Plasma levels of CD40 and soluble CD40 ligand were measured by enzyme linked immunosorbent assay in a single center cohort of 60 patients with renal artery stenosis recruited from Salford Royal Hospital, Manchester, UK. A natural log transformation of CD40 and soluble CD40 ligand was performed to normalize the data. Estimated glomerular filtration rate was used as the primary indicator of renal function. By univariate analysis low baseline levels of circulating CD40 (R(2)=0.06, p<0.05) and baseline creatinine (R(2)=0.08, p=0.022) were associated with loss of kidney function at one-year follow-up, whereas soluble CD40 ligand was not (R(2)=0.02, p=ns). In a multiple linear regression model CD40 (p<0.02) and baseline creatinine (p<0.01) continued to be significantly associated with a decline in renal function (model R(2)=0.17, p<0.005). Baseline CD40 levels were somewhat lower in patients who died during follow-up (survivors, 7.3 ± 0.9 pg/ml, n=48 vs. non-survivors, 6.7 ± 1.0 pg/ml, n=12, p=0.06). The CD40/soluble CD40 ligand signaling cascade may be a novel mechanism contributing to the development and progression of renal injury in patients with atherosclerotic renal artery stenosis