Search

Background: Pentoxifylline potently inhibits cell proliferation, inflammation, and extracellular matrix accumulation. Human studies have proved its antiproteinuric effect in patients with glomerular diseases. Its benefit in addition to angiotensin receptor blockade in patients with chronic kidney disease is not clear., Study Design: Randomized controlled study., Setting & Participants: 85 patients with estimated glomerular filtration rate (eGFR) of 10 to 60 mL/min/1.73 m(2) and proteinuria with protein greater than 500 mg/g of creatinine on treatment with losartan, 100 mg/d, for longer than 6 months were screened in National Taiwan University Hospital., Intervention: In the first stage (12 months), group 1 served as control and group 2 was administered pentoxifylline. In the second stage (6 months), both groups were administered pentoxifylline. The pentoxifylline dose was 400 mg twice daily for patients with eGFR of 30 to 60 mL/min/1.73 m(2) or once daily for patients with eGFR of 10 to 29 mL/min/1.73 m(2)., Outcomes: Proteinuria and eGFR., Measurements: Proteinuria was assessed as total protein-creatinine ratio, eGFR was computed by using the Modification of Diet in Renal Disease Study equation., Results: 27 and 29 patients were randomly assigned to groups 1 and 2, respectively. In the first stage, pentoxifylline decreased median proteinuria from 1,140 to 800 mg/g (median change, -23.9%) compared with 1,410 to 1,810 mg/g (median change, 13.8%) in the control group. The difference between groups was 38.7% (95% confidence interval, 25.7 to 51.6; P < 0.001). The change in proteinuria was related to the change in urinary tumor necrosis factor alpha and monocyte chemoattractant protein 1 excretion (R = 0.64 and R = 0.55, respectively; P < 0.001 for both). In the second stage, pentoxifylline reproduced the change in proteinuria in group 1., Limitations: Small sample size, disease of late stages, open-labeled study., Conclusions: Pentoxifylline added to losartan therapy for 1 year decreased proteinuria in patients with CKD stages 3 to 5. A large-scale clinical trial is necessary to confirm this result.

Background: Data about the relationship of inflammation to nephropathy in type 2 diabetes mellitus are scarce. In the present study, we test the hypothesis that inflammatory parameters are independently related to urinary albumin excretion (UAE) at early stages of nephropathy., Methods: Sixty-five patients with type 2 diabetes with microalbuminuria (MAB) or mild proteinuria (protein < 1 g/d) were included. We analyzed serum concentrations of high-sensitivity C-reactive protein (hs-CRP) and tumor necrosis factor-alpha (TNF-alpha), as well as urinary level of this cytokine., Results: Inflammatory parameters were significantly greater in patients with diabetes than controls; furthermore, urinary TNF-alpha levels increased significantly as nephropathy progressed. Median urinary TNF-alpha level was 7 pg/mg in normoalbuminurics, 13 pg/mg in microalbuminurics (P < 0.001), and 18 pg/mg in proteinurics (P < 0.001 versus normoalbuminuria and P < 0.01 versus MAB). Albuminuria was related to hs-CRP (r= 0.68; P < 0.001) and serum (r = 0.45; P < 0.01) and urinary TNF-alpha levels (r = 0.71; P < 0.001), but there was no association between serum and urinary TNF-alpha levels. Partial correlation analysis showed that hs-CRP level, urinary TNF-alpha level, duration of diabetes, and glycated hemoglobin level remained significantly associated with UAE. A stepwise multiple regression analysis showed that UAE was significantly associated with hs-CRP level (P < 0.001), duration of diabetes (P < 0.001), urinary TNF-alpha level (P < 0.01), and glycated hemoglobin level (P < 0.05; adjusted R2 = 0.73; P < 0.001)., Conclusion: Inflammatory parameters in patients with type 2 diabetes at an early stage of nephropathy are independently associated with UAE. In addition to traditional metabolic and hemodynamic factors, it is possible to hypothesize on the participation of inflammation in the pathogenesis of diabetic nephropathy.

Background: Cellular damage and inflammation after ischemia contribute to sustained acute renal failure (ARF)., Methods: To quantify cellular damage and inflammation in postischemic ARF and identify markers of renal functional outcome, urine specimens from 40 renal allograft recipients, including 30 cadaveric (9 "sustained ARF" and 21 "recovery" subjects) and 10 living donor allografts ("LD"), were analyzed for actin, gamma-glutamyl transpeptidase (GGTP), lactate dehydrogenase (LDH), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) and interleukin-8 (IL-8) during the first posttransplant week., Results: On day 0, urinary actin, GGTP, IL-6, and IL-8 were elevated in recipients destined to have sustained ARF compared with those destined to recover. Median values per gram of urine creatinine in the sustained ARF, recovery, and LD groups were 263.9, 0.0, and 0.0 microg for actin; 5000.0, 892.9, and 5555.6 U for GGTP; 193.1, 27.2, and 10.5 ng for IL-6; and 382.0, 17.8, and 18.5 ng for IL-8, respectively. In contrast, urinary LDH and TNF-alpha increased in recipients with recovering function compared with those who had sustained ARF. The corresponding median values were 36.7 and 16.3 U (recovery versus sustained ARF) for LDH, and 18.4 and 7.6 ng (LD versus sustained ARF) for TNF-alpha. Computational analyses using the Receiver Operating Characteristic Curve found that elevated urinary actin, IL-6, and IL-8 on day 0 were strong predictors of sustained ARF, where the calculated areas under the curve were 0.75, 0.91, and 0.82, respectively., Conclusion: Increased urinary actin, IL-6, and IL-8 may be useful markers for the prediction of sustained ARF after ischemia.