Antihypertensive regimens that include ACE inhibitors are more effective than regimens without ACE inhibitors in slowing the progression of nondiabetic renal disease. The beneficial effect of ACE inhibitors is mediated by factors in addition to decreasing blood pressure and urinary protein excretion and is greater in patients with proteinuria. Angiotensin-converting inhibitors are indicated for treatment of nondiabetic patients with chronic renal disease and proteinuria and, possibly, those without proteinuria.

Studies have shown that dual therapy with angiotensin-converting enzyme inhibitors (ACEI) and either angiotensin II receptor blockers or aldosterone receptor antagonists is more effective in reducing proteinuria than either agent used alone. The questions that remain are as follows: (1) Which of these agents should be used as dual therapy with the ACEI? (2) Does a higher level of blockade of the renin-angiotensin-aldosterone system with triple therapy offer an advantage over dual blockade? A 3-mo randomized, double-blind, placebo-controlled study was performed in 41 patients with proteinuria >1.5 g/d. Four treatment groups were compared: (1) Ramipril ؉ spironolactone placebo ؉ irbesartan placebo, (2) ramipril ؉ irbesartan ؉ spironolactone placebo, (3) ramipril ؉ irbesartan placebo ؉ spironolactone, and (4) ramipril ؉ irbesartan ؉ spironolactone. The percentage change in protein excretion differed according to treatment arm (ANOVA: F 3,35 ‫؍‬ 8.6, P < 0.001). Pair-wise comparison showed that greater reduction in protein excretion occurred in treatment regimens that incorporated spironolactone. The reduction in proteinuria at 3 mo was as follows: Group 1, 1.4%; group 2, 15.7%; group 3, 42.0%; and group 4, 48.2%. The reduction in proteinuria among patients who were taking spironolactone-containing regimens was sustained at 6 and 12 mo. This study suggests that aldosterone receptor blockade offers a valuable adjuvant treatment when used with ACEI therapy for the reduction of proteinuria. Results suggest no advantage of triple blockade over dual blockade of the renin-angiotensin-aldosterone system to reduce proteinuria.

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Marked changes in the accumulation of Mo/Mphi, MF, and collagen IV were found in this model of ischemic acute renal failure. The reversibility of functional and structural changes is in marked contrast to that found in progressive disease. The increases observed for collagen III at 64 and 180 days postischemia suggest that in the long term, however, further chronic structural changes may be observed.

Suppression of the humoral immune response by MMF has implications for the design of immunization protocols to protect the immunosuppressed, and raises the possibility that MMF use may be accompanied by more or different infections than complicate more conventional immunosuppression. More importantly, consideration should be given to harnessing the relatively specific effect of MMF on antibody production to treat antibody-mediated diseases.

Progressive renal failure results from a triad of glomerulosclerosis, tubulointerstitial fibrosis and vascular sclerosis. The mechanisms by which tubules are injured, and by which the tubular epithelial cell then excites interstitial inflammation culminating in fibroblast activation and fibrosis have become increasingly understood. Most current methods to prevent progressive glomerulosclerosis would inherently prevent tubular injury and interstitial fibrosis. The behaviour and control of the renal fibroblast is being investigated, with the potential for direct interference with its functions.

The Kidney Disease: Improving Global Outcomes Clinical Practice Guideline for management of blood pressure (BP) in chronic kidney disease (CKD) supersedes the 2004 Kidney Disease Quality Outcomes Initiative document on this topic. The new guideline has been designed to assist clinical decision making in patients with CKD who are not receiving dialysis. The recommendations in the guideline acknowledge that no single BP target is optimal for all CKD patients and encourage individualization of treatment depending on age, the severity of albuminuria, and comorbidities. In general, the available evidence indicates that in CKD patients without albuminuria the target BP should be ≤140 mm Hg systolic and ≤90 mm Hg diastolic. However, in most patients with an albumin excretion rate of ≥30 mg/24 h (i.e., those with both micro- and macroalbuminuria), a lower target of ≤130 mm Hg systolic and ≤80 mm Hg diastolic is suggested. In achieving BP control, the value of lifestyle changes and the need for multiple pharmacological agents is acknowledged. Use of agents that block the renin-angiotensin-aldosterone system is recommended or suggested in all patients with an albumin excretion rate of ≥30 mg/24 h. Recommendations are almost identical in CKD patients with and without diabetes. Special considerations relevant to children and those of older age and those who have received a kidney transplant are included. Ongoing controversies in BP management in the context of CKD are highlighted along with key areas for future research.