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                                      TITLE PAGE


      Yung-Hsin Huang1, Yi-Chou Chen1, Huang-Yang Tseng2, Chih-Jen Wu1,3,4 ,
                                  Han-Hsiang Chen1,3,5

Division of Nephrology, Department of Internal Medicine, Mackay Memorial Hospital,
Taipei, Taiwan1
Division of Nephrology, Department of Internal Medicine, Mackay Memorial Hospital,
Hsin-Chu, Taiwan2
Mackay Medicine, Nursing and Management College, Taipei, Taiwan3
Graduate Institute of Medical Science, Taipei Medical University, Taipei, Taiwan4
National Taipei College of Nursing, Taipei, Taiwan5

Correspondence and reprint requests to: Dr. Han-Hsiang Chen
Division of Nephrology, Department of Internal Medicine, Mackay Memorial Hospital.
No. 92, Section 2, Chung Shan North Road, Taipei, Taiwan.

 Running title : FSGS with reversible renal failure


                         TITLE PAGE (中文)


             黃永新 1, 陳逸洲 1, 曾黃泱 2, 吳志仁 1,3,4 , 陳漢湘1,3,5

馬偕紀念醫院, 腎臟內科 1
馬偕紀念醫院(新竹),腎臟內科 2
馬偕醫護管理專科學校 3
台北醫學大學醫學研究所 4
國立台北護理學院 5

抽印本索取及聯絡地址: 陳漢湘醫師
台北市中山區中山北路二段 92 號
電話 : (02) 25433535
傳真 : (02) 25433642





                  The nephrotic associated acute renal failure is an infrequent but an

alarming condition in primary or secondary glomerular diseases. Pathophysiology is

unclear and the following mechanisms may be proposed in causing acute decline in

glomerular filtration rate; a severe reduction of glomerular ultrafiltration, a concomitant

acute tubular injury and an increased intrarrenal pressure secondary to interstitial edema

and/or tubular obstruction. We present a 26-year-old young man with a nephrotic

syndrome caused by focal segmental glomerulosclerosis who developed an oliguric acute

renal failure. Renal function did not improve in spite of fluid removal by hemodialysis

and only after corticosteroid therapy we attained resolution of acute renal failure. Hence,

the steroid therapy is a worth giving strategy for recovery of renal function in such


Key    words:    Nephrotic    syndrome,     Acute    renal   failure,   Focal   segmental



                    ABSTRACT (中文)



      對 於 原 發 或 繼 發 性 腎 絲 球 疾 病 病 患 而 言 腎 病 症 候 群 (Nephrotic



內壓力增高可能是急性降低腎絲球過濾率(GFR)之機轉。我們提出一位 26 歲男性病

患, 以局部腎絲球硬化症(FSGS)引起之腎病症候群合併急性寡尿性腎衰竭為表現,




關鍵詞 : 腎病症候群, 急性腎衰竭, 局部腎絲球硬化症




          The development of acute renal failure (ARF) in patients with nephrotic

syndrome (NS) is an uncommon, but an important complication and the minimal change

disease is the frequently seen glomerulopathy1. Focal segmental glomerulosclerosis

(FSGS) may also present with ARF, but is less common. The underlying pathophysiology

is not clearly understood, but several mechanisms have been suggested for decrease in

glomerular filtration rate. The reduction in ultrafiltration of glomerular basement

membrane might play a major role2. Some postulated that it might be related to the

increase in hydrostatic pressure in the tubule and Bowman’s space due to obstruction by

protein cast and/or interstitial edema1. Furthermore, hypovolemia secondary to

hypoalbuminemia and/or the excessive use of diuretics could be a contributing factor3.

FSGS is considered to be more refractory to treatment than minimal change

glomerulopathy. Herein, we report a case of reversible ARF secondary to nephrotic

associated FSGS, after treatment with corticosteroid.


                                       Case report

      A 26-year-old man had past medical history of rheumatic heart disease status post

mitral and aortic mechanical valve replacement, atrial fibrillation and hypertension since

about 4 years ago. His current medications include coumadin 2.5 mg once daily,

propranolol 10 mg four times per day and oral furosemide 20 mg twice daily from other

hospital. He presented to our branch hospital with edema of lower legs for 1 week

duration. On admission, a blood pressure of 123/88 mmHg, a heart rate of 112/min, a

respiratory rate of 18/min, a temperature of 36 degree Celsius were recorded. Laboratory

data were as follows: serum blood urea nitrogen (BUN) 70 mg/dL, creatinine (Cr) 2.6

mg/dL, albumin 2.5 g/dL, total protein 6.9 g/dL, total cholesterol 293 mg/dL,

triglycerides 92 mg/dL, hemoglobin 9.8 gm/L, MCV 96.1 fl. WBC and platelet count

were within normal limits. Coagulation profile revealed prothrombin time (PT) 14.9

second (control 11.0), INR 1.73, activated partial thromboplastin time (APTT) 30.8

second (control 30.0). Urinalysis showed dipstick protein 3+, RBC 32/HPF. The spot

urine protein to creatinine ratio (UPCR) was 6.12. Immunological data showed IgG 619

mg/dL, IgA 405 mg/dL, IgM 209 mg/dL, C3 71 mg/dL, C4 33 mg/dL. Antinuclear factor,

rheumatoid factor, cryoglobulin, ANCA-C, ANCA–P, hepatitis B surface antigen and

hepatitis C antibody were all non-significant. Kidney sonography showed increased size

of both kidneys and normal cortical echogenicity. Echocardiography revealed prosthetic

mechanical mitral and aortic valves, preserved global systolic function with ejection

fraction 62%.

                Despite medical therapy with intravenous furosemide 40 mg per day since

admission, renal failure became worsening with persistent oliguria (Fig.1). On fourth


hospital day, urine amount was 330 ml per day while total intake was 1712 ml per day,

and serum BUN was elevated to 129 mg/dL, Cr to 3.1 mg/dL. So, hemodialysis was

arranged on that day and maintained regular three times a week as oliguria and high

azotemia continued (Fig.1). Then, corticosteroid pulse therapy with intravenous

methylprednisolone 1 gram per day was initiated for 3 consecutive days, followed by oral

prednisolone 0.5 mg/kg/day dose. Urine output was increased day by day after giving

corticosteroid therapy, so hemodialysis was discontinued and renal function was

recovered gradually. But, the proteinuria was slow to reach complete remission. The

UPCR was 1.24 after about 8 weeks of corticosteroid therapy, so renal biopsy was

performed at our main hospital. The specimen contained a total of 20 glomeruli. The light

microscopy showed some glomeruli with segmental sclerosis, renal tubules with

thickened basement membrane, but unremarkable interstitium (Fig.2). There were no

staining for immunoglobulins or complement under immunofluorescence microscopy.

Electron microscopy revealed no electron-dense deposits and the foot processes of

podocytes showed effacement. The pathological diagnosis was FSGS. We are continuing

corticosteroid therapy for non-nephrotic range proteinuria.



              Our patient mainly presented with NS associated ARF and oliguria

necessitating hemodialysis for about 4 weeks. Renal function was recovered after

corticosteroid therapy, but remission of proteinuria was rather slow. So, renal biopsy was

done and unveiled FSGS.

              In clinical practice, NS associated ARF is mostly seen in minimal change

glomerulopathy. Other NS predorminant glomerulonephritis conditions like FSGS may

evolve with ARF, but is less often. Pure membranous glomerulopathy causing ARF is

very rare. Only when it is superimposed with a crescentic glomerulonephritis, then

presents with ARF, active urinary sediments and cellular casts4. Aggressive

glomerulonephritis like rapidly progressive glomerulonephritis usually happens to ARF

but with different mechanism, the crescent formation. Apart from underlying

glomerulonephritis pathophysiology, some patients with NS concurrently using

nonsteroidal antiinflammatory drugs5, or selective COX-2 inhibitors6, or traditional

medicine7, or exposing to iodinated contrast medium8, may develop ARF mostly

secondary to an acute or chronic tubulo-interstitial nephropathy. Our patient did not have

exposure to these conditions and to ACEI/ARB in the history and throughout

hospitalization. Moreover, there were no signs of intravascular volume depletion on

admission and we only prescribed 40mg of furosemide per day in order to avoid

diuretics-overuse related worsening of renal failure. Although maintaining daily positive

fluid balance since admission, renal function did not improve. Our limitation was the

time-lag of renal biopsy which was actually done on 90th day of disease course. The


histopathology could not reveal any superimposed tubulo-interstitial change at that time

even if it initially coexisted. But, we did not find any evidence of its coexistence

clinically from history and disease course. We assumed that the possibility of coexistence

of toxin or drug related tubulo-interstitial nephropathy in our patient might be much less

than the underlying glomerulonephritis alone.

               In literature reports, high risk of ARF is found in nephrotic patients who

tend to be much older1, have more marked proteinuria with hypoalbuminemia and a

higher blood pressure9. The pathogenesis is uncertain, but the proposed etiologies may

include reduced glomerular ultrafiltration due to foot process fusion2, early transient

ischemic tubular injury causing decreased nephronal perfusion9,10, interstitial edema

known as nephrosarca11, obstructing intratubular protein debris9. Ischemic tubular injury

hypothesis is less likely in this case because our patient did not have hypotension or other

shock episode in the history and during hospital course. Although our patient is young

and has easily controllable blood pressure, the extent of proteinuria is high, which

suggests a more severe presentation of the underlying FSGS, causing severe reduction in

glomerular ultrafiltration. Corticosteroid therapy induces a recovery of renal function

with improvement in underlying disease by decreasing proteinuria12. The detail

mechanism of corticosteroid on glomerular ultrafiltration in ARF secondary to NS

remains unknown, but it may permit the complete recovery of glomerular filtration

fraction as proteinuria decreases13. Meanwhile, the appropriate diuretic therapy or renal

replacement therapy should be initiated and maintained for removal of excess fluid

causing interstitial edema, in order to avoid a misbalance of pressures within the

glomeruli and the subsequent progression to anuria.


               Patients with primary FSGS may present with any level of proteinuria,

nevertheless, the concern is greatest for those who present with nephrotic-range

proteinuria and renal dysfunction because without appropriate treatment, they often

follows an alarming progressive course to ESRD over three to six years14. The rate of

spontaneous complete remission among patients with NS related FSGS is very low,

probably less than 10%15. Spontaneous remission is more likely to occur among patients

with normal kidney function and non-nephrotic proteinuria15. Although optimal dose and

duration of corticosteroid therapy are unknown, better results are obtained with an

aggressive longer course of therapy rather than conventional short periods of 8 to 12

weeks in patients with nephrotic range proteinuria. Up to almost 70% of patients with

nephrotic associated FSGS may attain complete or partial proteinuric remission and

maintain stable renal function for about 10 years when given a prolonged therapy with

corticosteroid or immunosuppressive drugs16. The last UPCR of our patient declined to

0.7 after 16 weeks of steroid therapy.

               In conclusion, the renal replacement therapy may be required in case of

nephrotic associated ARF secondary to FSGS, especially when presenting with oliguria

and accumulation of nitrogen products. At the same time, corticosteroid treatment with

adequate dose should be initiated or treatment duration prolonged for better benefit.

Consequently, the reversibility of ARF might be expected as in our case.



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                                  FIGURE LEGEND


Fig.1. The serial alterations of serum BUN, serum Cr and urine amount per day are

shown in relation to days of clinical course. The time period under the dotted square area

represents regular hemodialysis period. Recovery of renal function after steroid therapy is


Fig.2. Renal histopathology (Hematoxylin & eosin x 200 magnification) reveals one

glomerulus with segmental sclerosis. The basement membrane is thickened in some renal

tubules. The interstitium is unremarkable.


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