ISCHEMIC NEPHROPATHY

LIGIA PETRESCU

DEFINITION
The term "ischemic nephropathy" refers to the reduction in GFR that is caused by hemodynamically significant renal artery obstruction. The most common cause of ischemic renal disease in adults is bilateral atheromatous disease when both kidneys are present or unilateral stenosis in a solitary kidney.
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DEFINITION
The major clinical questions confronting the nephrologist in considering the diagnosis of ischemic nephropathy include:
1. What is its prevalence in the population with end-stage renal disease? 2. What is the natural history in patients with less severe renal insufficiency? 3. Which clinical and laboratory features are most useful in its detection? 4. What are the indications for renal artery revascularization? 5. Which method of revascularization is more effective?
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EPIDEMIOLOGY
Hypertension is reportedly a common cause of end-stage renal disease, second only to diabetic nephropathy. During the past decade, the frequency of endstage renal disease attributed to hypertension has increased fivefold, and during the past 5 years, its prevalence has increased by more than 10%/y. The median age of this group is 67 years at the time of the initiation of dialysis, which is among the oldest for all causes of end-stage renal disease.

EPIDEMIOLOGY

The median survival for patients with ischemic nephropathy was 27 months, compared with 56 months for the other diagnostic groups. Furthermore, the 5-year survival was 12% compared with 39% for the other groups. This poor outcome was attributed to the increasing age of the patients at the time of initiation of dialysis (46 to 60 years) and their advanced systemic atherosclerosis. Compared with a group in whom other causes of chronic renal disease were found, those with ischemic nephropathy were
older, had more systemic atherosclerosis, had a threefold higher frequency of deterioration of GFR after treatment with an ACE inhibitor.

EPIDEMIOLOGY
These lesions were invariably located at the aortic orifice or within the proximal third of the renal artery. Renovascular stenosis is often found unexpectedly during the evaluation of occlusive disease of the aorta and lower extremities.

NATURAL HISTORY
There is compelling evidence that ischemic nephropathy is the consequence of progressive renal artery stenosis and occlusion. Angiographic progression of renal artery narrowing was found in 49% of 237 patients in five studies in which the follow-up period ranged from 6 to 180 months. However, there was considerable variability in the rate at which renal artery lesions progressed, ranging from approximately 1.5% to 5.0%/y. Progression to complete occlusion has been observed in approximately 15% of patients with renal artery stenosis. In contrast to these observations in patients with atheromatous lesions, fibromuscular dysplasia did not commonly progress to complete occlusion.
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DETECTION
Few clinical signs or noninvasive laboratory tests point to the diagnosis of ischemic nephropathy or signal its progression to occlusion. Clinical suspicion should be high in:
elderly patients with progressive renal insufficiency associated with an inactive urine sediment, protein excretion less than 1 g/d, hypertension, and peripheral vascular disease. a reduction in kidney length heralds progressive stenosis and occlusion, However, the sensitivity of these clinical and laboratory signs is relatively poor for identifying patients with ischemic nephropathy.
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DETECTION
Duplex ultrasonography detected a decrease in length greater than 1 cm in only 26% of those with progressive stenosis. Excretory urography and renal scintigraphy are inadequate for identifying patients with ischemic nephropathy. Changes in biochemical measurements are often unsatisfactory for detecting progressive disease. Serum creatinine concentration increased more commonly in patients with ongoing stenosis, this was not the case in other series. PRA, when measured during the captopril test or renal vein renin sampling, is less reliable for identifying bilateral renovascular stenosis than for unilaterallesions.
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Clinical Characteristics of Renovascular Hypertension

Characteristic

Essential Hypertension (%)

Renovascular Hypertension (%) Atheroma Fibromuscular Dysplasia

Race (black)
Family history Age at onset <20 y >50 y Duration >1 y Obese Abdominal bruit High-renin profile Hypokalemia (K+ <3.4 mEq/L) Smoking
Based on the US Cooperative Study

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67 12 7 10 38 7 15 7 42

2
58 2 39 23 17 41 80 14 88

10
41 16 13 19 11 57 80 17 71

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Pulmonary Edema

We have been impressed by the relatively frequent occurrence of pulmonary edema in patients with advanced renovascular hypertension. Successful revascularization of even one of the ischemic kidneys prevented further occurrence of the pulmonary edema. The occurrence of pulmonary edema was not related to the severity of the hypertension or renal failure. Although it was more common in patients who had associated coronary heart disease, it could also occur in patients with normal coronary arteries.
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THERAPEUTIC STRATEGIES FOR PRESERVATION OF RENAL FUNCTION

Medical Therapy Medical treatment does not reliably prevent the progression of renal artery stenosis, and it is associated with a high mortality rate after initiation of dialysis. Furthermore, the rate of progression of renal insufficiency often accelerates during antihypertensive drug treatment in patients with ischemic renal disease. This is a well-recognized complication of ACE inhibitor therapy, especially in the setting of Na+ depletion when the GFR is especially dependent on angiotensin II. Accordingly, acute deterioration is most likely to be provoked by ACE inhibitors during diuretic therapy, dietary sodium restriction, or excessive extrarenallosses (e.g., vomiting, diarrhea).

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THERAPEUTIC STRATEGIES FOR PRESERVATION OF RENAL FUNCTION

Other classes of antihypertensive agents can also cause acute renal failure: acute blood pressure reduction with nitroprusside (to approximately 145/85 mmHg) caused significant decrements in GFR and renal plasma flow. There are individual patients for whom medical therapy is selected because more invasive procedures may pose unacceptable risks. In this group, renal function should be observed closely while the patient is receiving antihypertensive medication, especially when ACE inhibitors are used. Diuretics should not be used routinely in combination with ACE inhibitors in patients with ischemic nephropathy because of the increased risk of acute renal failure. 13

RENAL REVASCULARIZATION
Surgery Reports from uncontrolled retrospective studies have clearly documented that surgical revascularization can improve renal function in patients with ischemic nephropathy. Postoperative improvement, generally defined as a 20% decrease in serum creatinine concentration, was reported in more than half of the patients in nine studies

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RENAL REVASCULARIZATION
Some features that may predict successful restoration of renal function include
collateral circulation and nephrogram on angiography, renal length greater than 9.0 cm, lateralization of renin secretion, differential concentration of urine on split-function studies, and viable nephrons on biopsy examination.

However, these should serve only as general guidelines because they lack sufficient specificity and sensitivity to determine outcome.
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Renal Angioplasty
Angioplasty is effective for treating renovascular hypertension associated with atheromatous lesions.

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SUMMARY
Renovascular disease often causes hypertension that can be cured or improved by renal revascularization. Another important consequence of renal artery stenosis is ischemic nephropathy. This refers to the progressive deterioration in GFR that occurs when renal blood flow is impaired. Ischemic nephropathy is increasingly recognized as an important cause of end-stage renal disease that has a high mortality rate when treated conservatively. By contrast, clinical improvement is reported commonly after renal revascularization.
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SUMMARY
There are few reliable clinical or laboratory markers for ischemic nephropathy, so that angiography is usually required to confirm the diagnosis. However, the diagnosis is likely in the elderly patient with systemic atherosclerosis and hypertension in whom a rapid rise in serum creatinine concentration is associated with decreased renal length. Revascularization by either renal angioplasty or surgery can successfully preserve renal function in selected patients.
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