Objective: To investigate the association of renal impairment on functional outcome and complications in strokepatients treated with IV thrombolysis (IVT).
Methods: In this observational study, we compared the estimated glomerular filtration rate (GFR) with poor 3-month outcome (modified Rankin Scale scores 3–6), death, and symptomatic intracranial hemorrhage (sICH) based on the criteria of the European Cooperative Acute Stroke Study II trial. Unadjusted and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Patients without IVT treatment served as a comparison group.
Results: Among 4,780 IVT-treated patients, 1,217 (25.5%) had a low GFR (<60 mL/min/1.73 m2). A GFR decrease by 10 mL/min/1.73 m2 increased the risk of poor outcome (OR [95% CI]): (ORunadjusted 1.20 [1.17–1.24]; ORadjusted 1.05 [1.01–1.09]), death (ORunadjusted 1.33 [1.28–1.38]; ORadjusted 1.18 [1.11–1.249]), and sICH (ORunadjusted 1.15 [1.01–1.22]; ORadjusted 1.11 [1.04–1.20]). Low GFR was independently associated with poor 3-month outcome (ORadjusted 1.32 [1.10–1.58]), death (ORadjusted 1.73 [1.39–2.14]), and sICH (ORadjusted 1.64 [1.21–2.23]) compared with normal GFR (60–120 mL/min/1.73 m2). Low GFR (ORadjusted 1.64 [1.21–2.23]) and stroke severity (ORadjusted 1.05 [1.03–1.07]) independently determined sICH. Compared with patients who did not receive IVT, treatment with IVT in patients with low GFR was associated with poor outcome (ORadjusted 1.79 [1.41–2.25]), and with favorable outcome in those with normal GFR (ORadjusted 0.77 [0.63–0.94]).
Conclusion: Renal function significantly modified outcome and complication rates in IVT-treated stroke patients. Lower GFR might be a better risk indicator for sICH than age. A decrease of GFR by 10 mL/min/1.73 m2 seems to have a similar impact on the risk of death or sICH as a 1-point-higher NIH Stroke Scale score measuring stroke severity.
Lipid peroxidation impairs renal function. Aldosterone contributes to renal injury in the remnant kidney model. This study aimed to determine the effects of the antioxidant N-acetylcysteine (NAC) on renal function and aldosterone levels in chronic renal failure.
Adult maleWistar rats were submitted to 5/6 nephrectomy or laparotomy (sham-operated) and received NAC (600 mg/L in drinking water, initiated on postoperative day 7 or 60), spironolactone (1.5 g/kg of diet initiated on postoperative day 7), the NAC-spironolactone combination or no treatment. Clearance studies were performed on postoperative days 21, 60, and 120.
Mean daily NAC and spironolactone ingestion was comparable among the treated groups. Mean weight gain was higher in NAC-treated rats than in untreated rats. A significant decrease in urinary thiobarbituric acid reactive substances (TBARS) concentrations, a lipid peroxidation marker, was observed in NAC-treated rats. By day 120, glomerular filtration rate (GFR), which dropped dramatically in untreated rats, was stable (albeit below normal) in NAC-treated rats, which also presented lower proteinuria, glomerulosclerosis index, and blood pressure, together with attenuated cardiac and adrenal hypertrophy. These beneficial effects, observed even when NAC was initiated on postnephrectomy day 60, were accompanied by a significant reduction in plasma aldosterone and urinary sodium/potassium ratio. The NAC-spironolactone combination lowered blood pressure and improved GFR protection.
The NAC-spironolactone combination improves renal function more than does NAC alone. In the remnant kidney model, early or late NAC administration has a protective effect attributable to decreased plasma aldosterone and lower levels of lipid peroxidation.
Our data demonstrate that NAC attenuates drops in GFR, as well as lowering proteinuria and blood pressure in nephrectomized rats. This is accompanied by a significant reduction in aldosterone levels. Our results indicate that ROS play an important role in the progression of chronic renal failure. It is evident that NAC has potential utility in preventing glomerulosclerosis and loss of kidney function in patients with chronic renal failure. The findings that NAC attenuated GFR drop and lowered proteinuria, even in end-stage chronic renal failure, and that the combination of NAC and spironolactone improves renal function more than does NAC alone have significant clinical implications.
Proteinuria and low estimated glomerular filtration rate (eGFR) should both be considered when assessing a patient’s risk for — and prognosis after — acute kidney injury, according to a large study presented at the American Society of Nephrology’s annual meeting and published online in the Lancet.
Among more than 900,000 adults in Canada tracked for some 35 months, risk for acute kidney injury requiring hospital admission or dialysis increased with increases in proteinuria alone and with decreases in eGFR alone; heavy proteinuria plus low eGFR conferred the highest risk. In turn, acute kidney injury was associated with increased mortality at all levels of proteinuria and eGFR, but particularly in patients with heavy proteinuria and normal eGFR.
Commentators conclude that “urine dipsticks … might just be what the doctor ordered for starting to reverse worldwide trends in acute kidney injury.”