Use of anti-inflammatory analgesics in sickle-cell disease.

WHAT IS KNOWN AND OBJECTIVE: Non-steroidal anti-inflammatory drugs (NSAIDs) have been commonly used to treat pain in sickle-cell disease (SCD), but NSAID use is associated with renal, gastrointestinal and cardiovascular toxicities. Our objective was to evaluate the use of aspirin and non-aspirin NSAIDs in SCD. COMMENT: Despite analgesic and anti-inflammatory benefits in SCD, non-aspirin NSAIDs are associated with renal, cardiovascular and gastrointestinal toxicities in this patient population. Aspirin may have less renal and cardiovascular toxicities. The different side effect profile of NSAIDs is related to the COX-1/COX-2 selectivity at their therapeutic doses. Individual risk factors and genetic biomarkers should be considered when selecting appropriate NSAIDs and their dose. WHAT IS NEW AND CONCLUSION: NSAIDs have the potential to be an important component of pain regimens in SCD, but the use of NSAIDs should be individualized based on potential side effects and patient risk factors and the lowest effective dose should be prescribed with proper monitoring in patients with SCD.

N-terminal prohormone brain natriuretic peptide as a predictor of cardiovascular disease and mortality in blacks with hypertensive kidney disease: the African American Study of Kidney Disease and Hypertension (AASK).

BACKGROUND: Higher levels of N-terminal prohormone brain-type natriuretic peptide (NT-proBNP) predict cardiovascular disease (CVD) in several disease states, but few data are available in patients with chronic kidney disease or in blacks. METHODS AND RESULTS: The African American Study of Kidney Disease and Hypertension trial enrolled hypertensive blacks with a glomerular filtration rate of 20 to 65 mL x min(-1) x 1.73 m(-2) and no other identified cause of kidney disease. NT-proBNP was measured with a sandwich chemiluminescence immunoassay (coefficient of variation 2.9%) in 994 African American Study of Kidney Disease and Hypertension participants. NT-proBNP was categorized as undetectable, low, moderate, or high. Proteinuria was defined as 24-hour urinary protein-creatinine ratio >0.22. A total of 134 first CVD events (CVD death or hospitalization for coronary artery disease, heart failure, or stroke) occurred over a median of 4.3 years. Participants with high NT-proBNP were much more likely to have a CVD event than participants with undetectable NT-proBNP after adjustment (relative hazard 4.0 [95% confidence interval [CI] 2.1 to 7.6]). A doubling of NT-proBNP was associated with a relative hazard of 1.3 (95% CI 1.0 to 1.6) for coronary artery disease, 1.7 (95% CI 1.4 to 2.2) for heart failure, 1.1 (95% CI 0.9 to 1.4) for stroke, and 1.8 (95% CI 1.4 to 2.4) for CVD death. The association of NT-proBNP with CVD events was significantly stronger (P(interaction)=0.05) in participants with than in those without proteinuria. Higher NT-proBNP was not associated with renal disease progression. CONCLUSIONS: These results suggest that elevated NT-proBNP levels are associated with higher CVD risk among blacks with hypertensive kidney disease. This association may be stronger in individuals with significant proteinuria.

Correlation between pulse wave velocity and other measures of arterial stiffness in chronic kidney disease.

AIM: Pulse wave velocity (PWV), augmentation index (AIx) and time to first wave reflection (Tr) are all measures of arterial stiffness, but whether these parameters behave similarly in different populations is not well-understood. Given the large burden of cardiovascular disease in individuals with chronic kidney disease (CKD), assessing the relationship between vascular stiffness parameters in this population is important. METHOD: A subset of 152 participants enrolled in the Chronic Renal Insufficiency Cohort Study had vascular stiffness parameters (aortic PWV, central AIx, and Tr) measured using the SphygmoCor system. Linear association between these parameters was assessed using Pearson correlation coefficients. Reproducibility across operators of the device was also tested within individuals. RESULTS: Association was largest between PWV and heart rate-adjusted AIx (AIx-75). The correlation coefficient was 0.371 (p = 0.0003) for ideal studies and 0.305 (p = 0.0001) for all technically acceptable studies. The association between ideal PWV and AIx-75 measurements was 0.361 (p = 0.005) for men and 0.423 (p = 0.01) for women. Bland-Altman plots comparing the mean value of PWV (n = 31) or AIx-75 (n = 21) when measured by 2 different individuals against the difference in their respective values demonstrate that both measures of arterial stiffness are reproducible across multiple technicians. CONCLUSIONS: Thus, we conclude that PWV and AIx-75, despite measuring different quantities in different units, are related measures of arterial stiffness and are reproducible across multiple operators in the population with CKD.

Renal risk and renoprotection among ethnic groups with type 2 diabetic nephropathy: a post hoc analysis of RENAAL.

Type 2 diabetes is becoming the leading cause of end-stage renal disease (ESRD) worldwide. Prevalence of ESRD and the antihypertensive response to renin-angiotensin system intervention are suggested to vary among different ethnicities. The Reduction in Endpoints in Non-insulin dependent diabetes mellitus with the Angiotensin II Antagonist Losartan (RENAAL) study, which included different ethnic groups, demonstrated a renoprotective effect of losartan. A post hoc analysis from RENAAL was performed where we examined in each ethnic group the ESRD risk, identified independent predictors for ESRD, effect of degree of baseline albuminuria, effect of 6-month antiproteinuric response to therapy on ESRD, and renoprotective effect of losartan assessed by albuminuria reduction and ESRD. Baseline albuminuria was the strongest predictor for ESRD in every ethnic group. Albuminuria reduction was associated with reduced risk of ESRD while losartan reduced albuminuria in every ethnic group. When accounting for independent predictors of ESRD, losartan exhibited renoprotection in all ethnic groups. In this type 2 diabetic population with nephropathy, baseline albuminuria is the predominant risk parameter for ESRD; early antiproteinuric effect of losartan predicts long-term renoprotection; and losartan appears to be renoprotective in all ethnic groups. Since the RENAAL study was not powered to determine ethnic responses, these results underline the need for prospective trials where the aim is renal protection among different ethnic groups.

Effects of aging and drugs on normal renal function.

The aging kidney is associated with a number of structural and functional changes. As a result of these changes the aging kidney is more susceptible to nephrotoxic and ischemic injury. We will review the structural and functional changes that occur with aging and then review the salient features of acute renal failure in the elderly population.

Mesangial lupus nephritis with associated nephrotic syndrome.

Patients with mesangial proliferative lupus glomerulonephritis (World Health Organization class II) are generally believed to have only mild to moderate proteinuria and normal renal function. However, there have been several reports of patients with mesangial lupus with nephrotic-range proteinuria. In this report, we present two additional cases and review the literature. Of seven reported cases, persistent nephrotic syndrome was observed in four, morphologic transformation occurred in three, and all but one presented with varying degrees of azotemia. These cases reinforce the concept that in systemic lupus erythematosus, laboratory findings may not correlate well with the underlying glomerular lesion, and therefore, the renal biopsy is an essential clinical tool in the approach to lupus nephritis.

Laboratory evaluation of renal tubular acidosis.

In this article, the renal tubular acidoses are briefly described, individual laboratory tests of urinary acidification are reviewed, and the administration and interpretation of these tests are discussed. A systematic approach to the laboratory evaluation of hyperchloremic metabolic acidosis is included.