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Acute kidney injury (AKI) in minimal change disease and other forms of nephrotic syndrome

Alain Meyrier, MD
Section Editors
Richard J Glassock, MD, MACP
Fernando C Fervenza, MD, PhD
Deputy Editor
Albert Q Lam, MD


Although the glomeruli are normal on light microscopy in minimal change disease (MCD) at the time of presentation, many adults and children have a modest reduction (averaging 30 percent) in glomerular filtration rate (GFR), as evidenced by a moderate elevation in the plasma creatinine concentration [1-6]. This relatively common change is mediated at least in part by the reversible podocyte foot process fusion, which is apparent by electron microscopy, and which is characteristic of the disease [7-11]. In addition to this modest reduction in GFR, some patients with MCD develop acute kidney injury (AKI), which is often severe and may require dialysis [12-14]. In most cases, AKI is due to acute tubular necrosis.

The pathophysiology, etiology, clinical manifestations, and treatment of GFR reduction in patients with MCD are discussed in this topic. The pathophysiology and treatment of edema in such patients, as well as treatment of MCD in children and adults, are presented elsewhere. (See "Pathophysiology and treatment of edema in patients with the nephrotic syndrome" and "Treatment of idiopathic nephrotic syndrome in children" and "Treatment of minimal change disease in adults".)


Many patients with minimal change disease (MCD) and nephrotic syndrome have a modest reduction in glomerular filtration rate (GFR) of approximately 30 percent [1-6]. Studies of children with this disorder show a close correlation of the GFR with both the reduced filtration fraction and the decreased serum albumin concentration that are proportional to the severity of the nephrotic state. [6-8,10]. Filtrate that has passed through the glomerular basement membrane enters the urinary space via the slit pores between the adjacent foot processes. Foot process fusion decreases the filtration slit frequency, thereby increasing the average path length for filtration [7,8,10]. The capacity of the glomerular basement membrane to bar the egress of serum albumin into Bowman's space is altered, causing massive proteinuria, while foot process fusion reduces the glomerular capillary wall permeability to water and small solutes, decreasing hydraulic permeability and explaining the reduction in the GFR.

Low effective arterial blood volume is not the cause of reduced GFR in most patients with MCD. Although patients with MCD have a low plasma oncotic pressure, the "underfill" hypothesis that was thought to explain the reduction in GFR and the intense renal sodium reabsorption is no longer accepted [15-32]. Rather, in this particular edematous state, an increase in the interstitial pressure is accompanied by an increase of the lymph flow to the circulation that maintains a normal blood volume. These changes in renal function regress with treatment-induced remission of proteinuria. (See "Pathophysiology and treatment of edema in patients with the nephrotic syndrome".)

In some patients with MCD (usually adults), an acute onset of a severe decline in GFR is seen, possibly requiring dialysis. As noted below, hypertension and older age are risk factors for acute kidney injury (AKI) in patients with MCD. In several studies, for example, kidney biopsies performed in patients with MCD and AKI revealed vascular lesions of arterial and arteriolar sclerosis, which are commonly found in hypertensives [13,33]. These lesions of the renal vessels contribute to reduced blood flow to the glomeruli [34], which diminish in number with aging [35]. In addition, tubulointerstitial lesions are common with hypertensive nephrosclerosis [34]. Underlying vascular disease and tubulointerstitial lesions may be an important precursor to the development of AKI in patients with MCD.

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Literature review current through: Nov 2017. | This topic last updated: Oct 19, 2016.
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