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Ambulatory blood pressure (BP) monitoring allows concurrent evaluation of BP control and nocturnal BP dipping status, both related to adverse outcomes. However, few studies have assessed the prognostic role of combining information on dipping status and achieved ambulatory BP in patients with chronic kidney disease (CKD).Prospective observational cohort study.906 patients with hypertension and CKD attending 1 of 3 Italian nephrology clinics.Four groups were defined by simultaneously classifying systolic ambulatory BP levels as being at goal (daytime SBP 135 and nighttime SBP 120 mm Hg) or above goal, and the presence or absence of nocturnal dipping (nighttime to daytime SBP ratio of 0.9 versus ≥0.9).The composite of time to initiation of maintenance dialysis or estimated glomerular filtration rate (eGFR) decline ≥50%, and the composite of fatal and nonfatal cardiovascular events.Multivariable Cox proportional hazards models were used to estimate risks of kidney disease progression and cardiovascular disease in the 4 exposure groups where nocturnal dipping with systolic ambulatory BP at goal was the reference group.The mean patient age was 63.8 years, 61% were male, and 26.4% had diabetes; eGFR was 41.1 ± 20.8 mL/min/1.73 mLack of a diverse cohort (all those enrolled were White). Residual uncontrolled confounding.Systolic ambulatory BP above goal or the absence of nocturnal dipping, regardless of ambulatory BP, is associated with higher risks of cardiovascular disease and kidney disease progression among patients with CKD.Among patients with chronic kidney disease (CKD), ambulatory blood pressure (BP) monitoring improves the identification of individuals at high risk of clinical disease outcomes. Those with uncontrolled ambulatory BP are known to have a higher risk of developing cardiovascular disease and kidney disease progression, particularly when their ambulatory BP does not decline by at least 10% at night. Whether this is also true for patients with presence of optimal ambulatory BP levels but a BP pattern of no nighttime decline is largely unknown. We measured ambulatory BP in 900 Italian patients with CKD and followed them for several years. We found that, independent of ambulatory BP level, the absence of nighttime reductions in BP was associated with worsening of CKD and more frequent cardiovascular events. The absence of nighttime declines in BP is an independent risk factor for adverse events among patients with CKD. Future studies are needed to examine whether treating the absence of nighttime declines in BP improves clinical outcomes.

Rationale & Objective: Data for the association of sex with chronic kidney disease (CKD) progression are conflicting, a relationship this study sought to examine. Study Design: Pooled analysis of 4 Italian observational cohort studies. Setting & Participants: 1,311 older men and 1,024 older women with estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m2 followed up in renal clinics. Predictor: Sex. Outcomes: End-stage kidney disease (ESKD), defined as maintenance dialysis or kidney transplantation, as the primary outcome; all-cause mortality and eGFR decline as secondary outcomes. Analytical Approach: Cox proportional hazard analysis to estimate the relative risk for ESKD and mortality and linear mixed models to estimate the rate of eGFR decline. Results: Age, systolic blood pressure, and use of renin-angiotensin system inhibitors were similar in men and women. Baseline eGFRs were 27.6 ± 10.2 in men and 26.0 ± 10.6 mL/min/1.73 m2 in women (P < 0.001), while median proteinuria was lower in women (protein excretion, 0.45 [IQR, 0.14-1.10] g/d) compared with men (0.69 [IQR 0.19-1.60] g/d; P < 0.001). During a median follow-up of 4.2 years, 757 developed ESKD (59.4% men) and 471 died (58.4% men). The adjusted risks for ESKD and mortality were higher in men (HRs of 1.50 [95% CI, 1.28-1.77] and 1.30 [95% CI, 1.06-1.60], respectively). This finding was consistent across CKD stages. We observed a significant interaction between sex and proteinuria, with the risk for ESKD in men being significantly greater than for women at a level of proteinuria of ∼0.5 g/d or greater. The slope of decline in eGFR was steeper in men (−2.09; 95% CI, −2.21 to −1.97 mL/min/1.73 m2 per year) than in women (−1.79; 95% CI, −1.92 to −1.66 mL/min/1.73 m2 per year; P < 0.001). Although sex differences in eGFR decline were not different across CKD stages (P = 0.3), the difference in slopes between men and women was progressively larger with proteinuria > 0.5 g/d (P = 0.04). Limitations: Residual confounding; only whites were included. Conclusions: Excess renal risk in men may, at least in part, be related to higher levels of proteinuria in men compared with women.

This pilot study shows that aliskiren with ACE-inhibitor/ARB therapy allows a clinically significant (22% at month 6) and persistent (up to month 12) decrease in proteinuria. The antiproteinuric effect was at least in part unrelated to the antihypertensive effect and small decrease in eGFR and instead may depend on enhanced suppression of intrarenal angiotensin II with more effective correction of glomerular hypertension.The magnitude of antiproteinuric response was greater in younger patients and those with higher sodium excretion and therefore intake.

Background In patients with primary glomerulonephritis (GN), antiproteinuric response to angiotensin-converting enzyme (ACE) inhibitors plus angiotensin receptor blockers (ARBs) versus either monotherapy is undefined because of the small size of studies and high heterogeneity of response. Study Design Meta-analysis/metaregression. Setting & Population Randomized clinical trials (RCTs). Selection Criteria for Studies RCTs published from January 1996 to April 2007. Studies were excluded if information about levels of proteinuria was not available, patients had kidney disease other than primary GN, or if they had end-stage renal disease. Intervention ACE inhibitor plus ARB versus monotherapy with 1 of these drug classes. Outcomes Absolute changes in proteinuria (primary), blood pressure, serum potassium level, and glomerular filtration rate (GFR; secondary). Results We found 13 RCTs including 425 patients with primary GN with proteinuria ranging from 0.8 to 7.9 g/d of protein and age from 25 to 60 years. Combination treatment decreased proteinuria by 0.60 g/d (95% confidence interval, 0.40 to 0.80) versus ACE-inhibitor monotherapy and 0.54 g/d (95% confidence interval, 0.30 to 0.78) versus ARB monotherapy. Baseline levels of proteinuria explained most between-study variability of the antiproteinuric response to combination therapy versus monotherapies. Systolic and diastolic blood pressure, GFR, age, and diagnosis of immunoglobulin A nephropathy did not modify antiproteinuric response. ACE-inhibitor plus ARB therapy did not change GFR, whereas it increased serum potassium levels (by 0.10 mEq/L versus ACE-inhibitor and 0.19 mEq/L versus ARB therapy) and decreased blood pressure. Limitations Only published data are included. Conclusions The antiproteinuric response to ACE-inhibitor plus ARB therapy versus either monotherapy is consistently greater and strictly related to baseline proteinuria, associated with only moderate increase in serum potassium levels, and not peculiar to immunoglobulin A nephropathy.