Proteinuria as a modifiable risk factor for the progression of non-diabetic renal disease

Jafar, Tazeen H.; Stark, Paul C.; Schmid, Christopher H.; Landa, Marcia; Maschio, G; Marcantoni, Carmelita; Jong, Paul E. de; Zeeuw, Dick de; Shahinfar, Shahnaz; Ruggenenti, Piero; Remuzzi, Giuseppe; Levey, Andrew S.

doi:10.1046/j.1523-1755.2001.0600031131.x

Cited by 347 publications

(195 citation statements)

References 22 publications

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“…The African-American Study of Kidney Disease (AASK) recently reported that among African Americans with nondiabetic CKD, ramipril, an ACE inhibitor, was superior to a regimen that initiated therapy with either amlodipine, a dihydropyridine calcium antagonist, or metoprolol, a beta-blocker, for slowing the loss of kidney function and prevention of kidney-related clinical events (32). Furthermore, AASK study trial results were consistent with a large body of clinical trial data in nondiabetic CKD in that the greatest relative superiority of the ACE inhibitor was among those with the highest levels of proteinuria (63). Also, note that only kidney-related but not overall cardiovascular events were reported in AASK and that there was virtually no difference in BP lowering in the amlodipine and ramipril treatment arms (5).…”

Section: Evidence That Bp Lowering Slows the Progressive Loss Of Kidnsupporting

confidence: 59%

“…Other strategies to lower urinary protein excretion include dietary sodium restriction (66,67) as well cessation of cigarette smoking (68,69) and weight loss (70,71). Reductions in urinary protein excretion correlate with slower loss of kidney function (32,34,63). The clinician should be aware that attainment of low target BP levels (Ͻ130 to 135/80 to 85 mmHg) will be accomplished only with prescription of multiple (typically 3 to 4), not solitary, antihypertensive drugs (72).…”

Section: Evidence That Bp Lowering Slows the Progressive Loss Of Kidnmentioning

confidence: 99%

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Prevention of Hypertension and Its Complications

Flack¹,

Peters²,

Shafi³

et al. 2003

Journal of the American Society of Nephrology

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Abstract. Hypertension is a nutritional-hygienic disease. Longterm caloric intake in excess of energy expenditures, chronic supraphysiological intake of dietary sodium, excessive alcohol consumption, and psychosocial stressors all contribute to the development of hypertension throughout the world. Elevated BP, particularly systolic BP, has been linked to multiple adverse clinical outcomes including stroke, heart failure, myocardial infarction, renal insufficiency/failure, peripheral vascular disease, retinopathy, dementia, and premature mortality. These undesirable clinical outcomes are typically, although not invariably, preceded by pressure-related target-organ injury such as left ventricular hypertrophy, renal insufficiency and proteinuria. The relation of BP and CKD and, in turn, the prevention of CKD or forestalling its progression by hypertension treatment, will be the focus of this manuscript. In hypertensive persons with reduced kidney function and/or proteinuria, lowering BP with multidrug therapy that is inclusive of pharmacologic modulators of the renin-angiotensin-aldosterone-kinin system is an effective strategy to forestall the progressive loss of kidney function. The totality of data support low therapeutic BP targets for persons with proteinuria Ͼ1 g/d.Nevertheless, in persons with CKD, even those with proteinuria below the dipstick positive level (approximately 300 mg/d or urine protein to creatinine ratio of 0.22), aggressive BP control also may be warranted because of the high risk of nonrenal cardiovascular disease. Multiple antihypertensive drugs will be required in the vast majority of patients with diabetes and/or reduced kidney function to attain BP goal. Renin-angiotensin system (RAS) modulator therapy is indicated among persons with diabetes mellitus and CKD. Available data support the use of angiotensin receptor blockers in persons with type 2 diabetes and overt nephropathy for preservation of kidney function. Among persons with type I diabetes with or without overt nephropathy, type 2 diabetes without overt nephropathy and in nondiabetic CKD, the available clinical data support the use of angiotensin-converting enzyme inhibitors as the RAS modulator of choice. Low therapeutic target BP levels Ͻ130/80 mmHg in persons with type 2 diabetes mellitus also appear warranted based on available data mostly for reducing the risk of nonrenal cardiovascular disease and overall mortality. Hypertension, like most cardiovascular conditions, is a nutritional-hygienic disease. The seeds of hypertension are rooted in physical inactivity, obesity, high caloric intake, and excessive dietary sodium intake as well as alcohol consumption. Genetic susceptibility to hypertension remains ill-defined; however, environmental exposures of gene-environment interactions can be favorably influenced by manipulation of lifestyle choices.Prevention of hypertension-related complications such as reduced kidney function depends on population-wide control of known hypertension risk factors. Population-based hypertension pr...

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Section: Evidence That Bp Lowering Slows the Progressive Loss Of Kidnsupporting

confidence: 59%

Section: Evidence That Bp Lowering Slows the Progressive Loss Of Kidnmentioning

confidence: 99%

Prevention of Hypertension and Its Complications

Flack¹,

Peters²,

Shafi³

et al. 2003

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

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“…Large scale clinical trials and a meta analysis confirmed the benefits of ACEIs against a variety of renal diseases with their antiproteinuric effects (14, 80,81). Furthermore, recent studies demonstrated that the greater beneficial effect of ACEIs in renal disease patients with higher baseline proteinuria could be explained by the greater antiproteinuric effects in these patients (82). Thus, one of the protective mechanisms of ACEIs and ARBs is the reduction of the amount of proteinuria.…”

Section: Treatment Targeting Proteinuric Tubulointerstitial Damagementioning

confidence: 99%

Mechanisms of Tubulointerstitial Injury in the Kidney: Final Common Pathways to End-stage Renal Failure

2004

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There are many different glomerular disorders, including glomerulonephritis, diabetic nephropathy, and hypertensive nephrosclerosis. However, once glomerular damage reaches a certain threshold, the progression of renal disease is consistent and irreversible. Recent studies emphasized the crucial role of tubulointerstitial injury as a mediator of progression of kidney disease. One common mechanism that leads to renal failure via tubulointerstitial injury is massive proteinuria. Accumulating evidence suggests critical effects of filtered macromolecules on tubular cells, including lysosomal rupture, energy depletion, and tubular injury directly induced by specific components such as complement components. Another common mechanism is chronic hypoxia in the tubulointerstitium. Tubulointerstitial damage results in the loss of peritubular capillaries, impairing blood flow delivery. Interstitial fibrosis also impairs oxygen diffusion and supply to tubular cells. This induces chronic hypoxia in this compartment, rendering a vicious cycle. Development of novel therapeutic approaches against these final common pathways will enable us to target any types of renal disease. (Internal Medicine 43: 9-17, 2004)

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“…[3][4][5][6] The presence of proteinuria, a marker of kidney damage, identifies patients at increased risk of adverse clinical outcomes, including progression to ESRD. [7][8][9][10][11][12] However, whether the effects of proteinuria on earlier signs of kidney damage, namely the rate of change in estimated GFR (eGFR), vary by baseline level of kidney function is less clear. A more detailed understanding of the relationship among proteinuria, kidney function, and progression of renal disease would permit the identification of those who are at greatest risk of a progressive decline in kidney function and aid in implementation of interventions to slow the progression or prevent the development of ESRD.…”

mentioning

confidence: 99%

Proteinuria and Rate of Change in Kidney Function in a Community-Based Population

Turin¹,

James

Ravani

et al. 2013

Journal of the American Society of Nephrology

108

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Proteinuria identifies patients at risk for adverse clinical outcomes, but it is unclear whether proteinuria correlates with the rate of renal decline. We examined the association between proteinuria and rate of change in estimated GFR (eGFR) in a cohort of 638,150 adults from a province-wide registry in Alberta, Canada, who had a measure of proteinuria and three or more outpatient serum creatinine measurements over a period of $1 year. An adjusted sex-specific linear mixed-effects model was used to determine the rate of change in eGFR per year for patients with normal, mild, and heavy proteinuria, stratified by baseline kidney function (eGFR $90, patients. Notably, normal protein levels and a lower baseline eGFR (15-29.9 ml/min per 1.73 m 2 ) correlated with stable or improved renal function. In conclusion, our results suggest that proteinuria of increasing severity is associated with a faster rate of renal decline, regardless of baseline eGFR, and the combined effect should be considered in patients with CKD.

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Proteinuria as a modifiable risk factor for the progression of non-diabetic renal disease

Cited by 347 publications

References 22 publications

Prevention of Hypertension and Its Complications

Prevention of Hypertension and Its Complications

Mechanisms of Tubulointerstitial Injury in the Kidney: Final Common Pathways to End-stage Renal Failure

Proteinuria and Rate of Change in Kidney Function in a Community-Based Population

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