Elsevier

The Lancet

Volume 357, Issue 9268, 19 May 2001, Pages 1601-1608
The Lancet

Review
Progression, remission, regression of chronic renal diseases

https://doi.org/10.1016/S0140-6736(00)04728-0Get rights and content

Summary

The prevalence of chronic renal disease is increasing worldwide. Most chronic nephropathies lack a specific treatment and progress relentlessly to end-stage renal disease. However, research in animals and people has helped our understanding of the mechanisms of this progression and has indicated possible preventive methods. The notion of renoprotection is developing into a combined approach to renal diseases, the main measures being pharmacological control of blood pressure and reduction of proteinuria. Lowering of blood lipids, smoking cessation, and tight glucose control for diabetes also form part of the multimodal protocol for management of renal patients. With available treatments, dialysis can be postponed for many patients with chronic nephropathies, but the real goal has to be less dialysis–in other words remission of disease and regression of structural damage to the kidney. Experimental and clinical data lend support to the notion that less dialysis (and maybe none for some patients) is at least possible.

Section snippets

Notion of renoprotection

Most renal diseases progress to renal failure as a consequence of functional adaptations intervening in the kidney, after the original disease process causes a critical loss of nephron units. Such changes, extensively studied in rats, include glomerular hyperperfusion and hypertension of the remaining nephrons, which to begin with enhance the filtration capacity of single nephrons. Over time, however, kidney hyperfiltration is detrimental.7 Renoprotection is a strategy that aims to interrupt or

Renoprotection by low-protein diet

Reduction of the amount of protein in the diet prevents disease progression in most animal models. Does this rule apply to man? A few initial study results showed a benefit but larger trials were less encouraging. In one controlled study8 of 456 patients, restriction of protein content alone showed a trend toward benefit, but inaccurate measurement of glomerular filtration rate (GFR) and non-compliance prevented clear-cut conclusions. Compliance was much better in the 585 patients without

Renoprotection by blood-pressure control

In animal models of chronic nephropathy, systemic hypertension is associated with increased intraglomerular pressure.2, 11, 12 Lowering blood pressure uniformly slows disease progression and reduces renal damage.11 Angiotensin-converting-enzyme (ACE) inhibitors are, among the antihypertensive drugs, those that most effectively lower intraglomerular capillary pressure in animals.11, 12 A seminal clinical study was published in 1976.13 Five patients with type 1 diabetes whose decline in renal

Duration of renoprotection

Parving and co-workers34 have reported a progressive reduction in the rate of GFR decline in nine patients with type 1 diabetes and overt nephropathy over 9 years of continuous antihypertensive therapy. 6 years later, Wilmer and colleagues35 described seven patients who had remission of nephrotic syndrome (proteinuria < 1 g) while on captopril, and who were available 7 years later for follow-up. One patient had progressed to ESRD but the others were still in remission (mean proteinuria 1·03 g,

Optimisation of blood-pressure control

A pooled analysis by Weidmann and co-workers37 established a strong relation between extent of blood-pressure control and proteinuria reduction in diabetic nephropathy. When blood-pressure control was tight, all antihypertensive drugs other than nifedipine significantly reduced proteinuria.37 How far should blood pressure be reduced? In the MDRD study,16 non-diabetic patients with GFR 13·55 mL/min were randomly assigned to a usual mean arterial pressure target of 107 mm Hg or less, or to a low

ACE inhibitors and angiotensin II receptor antagonists

Since ACE inhibitors and angiotensin II receptor antagonists inhibit the renin-angiotensin system at different points, they could act synergistically, and studies in rats42 point to less renal injury with this combination. However, combined treatment was associated with greater blood-pressure reduction than with each drug separately, and when drug doses were titrated to achieve comparable blood-pressure control, no significant differences in proteinuria and glomerulosclerosis between the

Experimental treatments

Besides angiotensin II, other peptides such as endothelin-1, and natriuretic peptides, might have a role in the progression of renal disease. Interference with the renal action of these peptides could represent an innovative strategy to slow the progression of chronic nephropathies.

No more dialysis for some?

Experimental and clinical studies indicate that renal disease progresses less rapidly in women than in men, and ACE inhibitors are more renoprotective in women.72 In the REIN study, ramipril decreased the rate of GFR decline and the frequency of ESRD by 52% and 74%, respectively, in women, but only by 19% and 40%, in men. ACE inhibition retained a better renoprotective effect in women even after adjustments for a series of potentially confounding factors including treatment compliance, dietary

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