Interpreting SPRINT: How low should you go?

The Systolic Blood Pressure Intervention Trial (SPRINT) found evidence of cardiovascular benefit with intensive lowering of systolic blood pressure (goal < 120 mm Hg) compared with the currently recommended goal (< 140 mm Hg) in older patients with cardiovascular risk but without diabetes or stroke. This article reviews the trial design and protocol, summarizes the results, and briefly discusses the implications of these results.

Pyridorin in type 2 diabetic nephropathy.

Pyridoxamine dihydrochloride (Pyridorin, NephroGenex) inhibits formation of advanced glycation end products and scavenges reactive oxygen species and toxic carbonyls, but whether these actions translate into renoprotective effects is unknown. In this double-blind, randomized, placebo-controlled trial, we randomly assigned 317 patients with proteinuric type 2 diabetic nephropathy to twice-daily placebo; Pyridorin, 150 mg twice daily; or Pyridorin, 300 mg twice daily, for 52 weeks. At baseline, the mean age ± SD was 63.9±9.5 years, and the mean duration of diabetes was 17.6±8.5 years; the mean serum creatinine level was 2.2±0.6 mg/dl, and the mean protein-to-creatinine ratio was 2973±1932 mg/g. Regarding the primary end point, a statistically significant change in serum creatinine from baseline to 52 weeks was not evident in either Pyridorin group compared with placebo. However, analysis of covariance suggested that the magnitude of the treatment effect differed by baseline renal function. Among patients in the lowest tertile of baseline serum creatinine concentration, treatment with Pyridorin associated with a lower average change in serum creatinine concentration at 52 weeks (0.28, 0.07, and 0.14 mg/dl for placebo, Pyridorin 150 mg, and Pyridorin 300 mg, respectively; P=0.05 for either Pyridorin dose versus placebo); there was no evidence of a significant treatment effect in the middle or upper tertiles. In conclusion, this trial failed to detect an effect of Pyridorin on the progression of serum creatinine at 1 year, although it suggests that patients with less renal impairment might benefit.

Sulodexide for kidney protection in type 2 diabetes patients with microalbuminuria: a randomized controlled trial.

BACKGROUND: Sulodexide, a heterogenous group of sulfated glycosaminoglycans, includes low-molecular-weight heparin (~80% ± 8%), high-molecular-weight heparin (~5% ± 3%), and dermatan (~20% ± 8%), with a mean molecular weight of ~9 kDa. The drug is absorbed orally and has no anticoagulant effect in the doses used. Small preliminary studies consistently showed sulodexide to be associated with decreased albuminuria in patients with diabetes. STUDY DESIGN: We conducted a multicenter placebo-controlled double-blinded study to determine the effect of sulodexide on urine albumin excretion in patients with type 2 diabetic nephropathy. SETTING & PARTICIPANTS: Patients with type 2 diabetes and urine albumin-creatinine ratios (ACRs) of 35-200 mg/g in men and 45-200 mg/g in women were enrolled. Serum creatinine level was <1.5 mg/dL. Blood pressure goal was 130/80 mm Hg. A maximum US Food and Drug Administration-approved dose of an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker for a minimum of 4 months before randomization was required. INTERVENTION: The study drug was sulodexide, 200 mg/d. OUTCOME & MEASUREMENTS: The primary end point was normoalbuminuria (ACR <20 mg/g and a decrease >25%) or 50% decrease in baseline ACR. RESULTS: In 1,056 randomly assigned patients with a mean baseline ACR of 107.8 ± 83.7 mg/g, comparing the sulodexide versus placebo groups, the primary end point was achieved in 16.5% versus 18.4%; normoalbuminuria, in 7.9% versus 6.1%; and a 50% decrease in albuminuria, in 15.4% versus 17.6%. The relative probability of any given change in albuminuria was identical in both groups. LIMITATIONS: We were unable to determine whether the administered sulodexide was absorbed from the gastrointestinal tract. CONCLUSION: Sulodexide failed to decrease urine albumin excretion in patients with type 2 diabetic nephropathy and microalbuminuria.

IgA-dominant Staphylococcus infection-associated glomerulonephritis: case reports and review of the literature.

Background and objectives. The mesangial deposition of IgA is rarely described with proliferative glomerulonephritis associated with Staphylococcus infection. Recently, this association has been increasingly recognized possibly due to the increased rate of Staphylococcus infection. Design setting, participants and measurements. We report two cases of methicillin-sensitive Staphylococcus aureus bacteremia associated with acute proliferative glomerulonephritis with dominant mesangial deposit of IgA. We searched MEDLINE (1960-2009) for similar reports. We pooled individual patient data and reported descriptive statistics of all published cases. Results. Forty-six cases were included in the final analysis. The mean age of presentation was 59, with a male predominance (84%). Clinical presentation was notable for rapidly progressive glomerulonephritis with nephrotic-range proteinuria and normal complement levels in 52 and 72%, respectively. Methicillin-resistant S. aureus (68%) was the most common pathogen isolated with a latent period ranging from 1 to 16 weeks. Diffuse mesangial proliferation was commonly found with crescentic lesions noted in 35% of the cases. Antimicrobial treatment was associated with renal recovery in 58% of the cases. Need for renal replacement therapy was significantly associated with pre-existing diabetes, hypertension and interstitial fibrosis seen on kidney biopsy. Conclusions. IgA-dominant post-Staphylococcus glomerulonephritis is a rare clinical entity with certain unique clinical and morphologic features. It is difficult to differentiate from primary IgA nephropathy in cases where the infection is not apparent. An acute onset of rapidly progressive glomerulonephritis, with normal complement levels and deposition of mesangial IgA in an elderly patient should raise suspicion for this rare form of glomerulonephritis.

Dipstick pseudohematuria: unnecessary consultation and evaluation.

PURPOSE: While many primary care providers advocate routine screening urinalyses, a heme positive dipstick test often leads to a false-positive diagnosis of hematuria, or pseudohematuria. Thus, American Urological Association guidelines recommend urological evaluation for asymptomatic patients only for at least 3 red blood cells per high power field in 2 of 3 microscopic urinalyses. We determined the percentage of patients referred for asymptomatic hematuria undergoing unnecessary consultation and studies. MATERIALS AND METHODS: Patients were retrospectively identified if seen for initial consultation associated with CPT 599.7X, hematuria. Among these patients those referred for evaluation of asymptomatic nonmacroscopic hematuria were identified, and referral patterns, ancillary tests, procedures and findings were examined. RESULTS: Of 320 new patient visits with diagnosis code 599.7X, 91 were referred for asymptomatic, nonmacroscopic hematuria. Of these patients only 37 (41%) had microscopic urinalyses before referral and only 22 (24%) had microscopic urinalyses showing 3 or more red blood cells per high power field. Of the 69 patients referred without confirmed microhematuria approximately 25% had true microhematuria and 15 with no true hematuria had undergone imaging before referral. The Medicare reimbursement value for the evaluation of these 69 patients was $44,901. Of these patients 35 underwent cystoscopy and only 1 (with true microhematuria) had a malignancy. CONCLUSIONS: Positive dipstick heme tests should always be confirmed by microscopic urinalysis before urological referral or evaluation. Education of referring physicians regarding the American Urological Association guidelines could possibly help limit costly and potentially harmful, unnecessary evaluation of patients without true microhematuria.

Use of endovascular stents in atherosclerotic renovascular stenosis: blood pressure and renal function changes in hypertensive patients.

Atherosclerotic renal artery stenosis may result in hypertension and ischemic nephropathy. Renal artery endovascular stenting has emerged as current therapy; however, the percentage of patients who benefit from this procedure is still not well established. The authors studied 116 hypertensive patients with atherosclerotic renovascular stenosis who underwent successful renal artery stenting for the first time. At 1 year, there was a significant overall decrease in blood pressure in the group after stenting; however, there was no change in renal function. Also, no significant change in the number of antihypertensive drugs was noted. Blood pressure improved in 55% of the patients, worsened in 14%, and remained unchanged in 31%. Renal function improved in 16% of the patients, worsened in 30%, and remained stable in 54%. In relation to blood pressure control, patients with resistant or difficult-to-control hypertension showed the most improvement in blood pressure control after stenting.

Independent and additive impact of blood pressure control and angiotensin II receptor blockade on renal outcomes in the irbesartan diabetic nephropathy trial: clinical implications and limitations.

Elevated arterial pressure is a major risk factor for progression to ESRD in diabetic nephropathy. However, the component of arterial pressure and level of BP control for optimal renal outcomes are disputed. Data from 1590 hypertensive patients with type 2 diabetes in the Irbesartan Diabetic Nephropathy Trial (IDNT), a randomized, double-blind, placebo-controlled trial performed in 209 clinics worldwide, were examined, and the effects of baseline and mean follow-up systolic BP (SBP) and diastolic BP and the interaction of assigned study medications (irbesartan, amlodipine, and placebo) on progressive renal failure and all-cause mortality were assessed. Other antihypertensive agents were added to achieve predetermined BP goals. Entry criteria included elevated baseline serum creatinine concentration up to 266 micromol/L (3.0 mg/dl) and urine protein excretion >900 mg/d. Baseline BP averaged 159/87 +/- 20/11 mmHg. Median patient follow-up was 2.6 yr. Follow-up achieved SBP most strongly predicted renal outcomes. SBP >149 mmHg was associated with a 2.2-fold increase in the risk for doubling serum creatinine or ESRD compared with SBP <134 mmHg. Progressive lowering of SBP to 120 mmHg was associated with improved renal and patient survival, an effect independent of baseline renal function. Below this threshold, all-cause mortality increased. An additional renoprotective effect of irbesartan, independent of achieved SBP, was observed down to 120 mmHg. There was no correlation between diastolic BP and renal outcomes. We recommend a SBP target between 120 and 130 mmHg, in conjunction with blockade of the renin-angiotensin system, in patients with type 2 diabetic nephropathy.

Impact of achieved blood pressure on cardiovascular outcomes in the Irbesartan Diabetic Nephropathy Trial.

Elevated arterial pressure enhances the risk for cardiovascular (CV) events in patients with diabetic nephropathy. The optimal BP and the component of the elevated BP that affect the risk have not been defined. A post hoc analysis was performed to assess the impact of achieved systolic, diastolic, and pulse pressures on CV outcomes in 1590 adults who had overt diabetic nephropathy and were enrolled in the Irbesartan Diabetic Nephropathy Trial (IDNT) and had a baseline serum creatinine above the normal range, up to 266 micromol/L (3.0 mg/dL), 24-h urine protein >900 mg/d, and at least 6 mo of follow-up. Patients were randomized to irbesartan, amlodipine, or placebo, with other antihypertensive agents to a BP goal of < or =135/85 mmHg. Progressively lower achieved systolic BP (SBP) to 120 mmHg predicted a decrease in CV mortality and congestive heart failure (CHF) but not myocardial infarctions (MI). A SBP below this threshold was associated with increased risk for CV deaths and CHF events. Achieved diastolic BP <85 mmHg was associated with a trend to increase in all-cause mortality, significant increase in MI, but decreased risk for strokes. Increased pulse pressure predicted increased all-cause mortality, CV mortality, MI, and CHF. It is concluded that achieved SBP approaching 120 mmHg and diastolic BP of 85 mmHg are associated with the best protection against CV events in these patients. BP < or =120/85 may be associated with an increase in CV events.

Relation of homocysteine and C-reactive protein to urinary albumin loss.

This study shows that elevated high-sensitivity C-reactive protein and plasma total homocysteine contribute independently to the likelihood of an increased urinary albumin:creatinine ratio. This result suggests that total homocysteine and C-reactive protein may be acting by separate mechanistic pathways.