• No results found

Focal Segmental Glomerulosclerosis and Progressive Renal Failure Associated with a Unilateral Kidney

N/A
N/A
Protected

Academic year: 2020

Share "Focal Segmental Glomerulosclerosis and Progressive Renal Failure Associated with a Unilateral Kidney"

Copied!
7
0
0

Loading.... (view fulltext now)

Full text

(1)

Focal

Segmental

Glomerulosclerosis

and

Progressive

Renal

Failure

Associated

with a

Unilateral

Kidney

Paul S. Thorner,

MD, Gerald

S. Arbus,

MD, David

S. Celermajer,

and

Reuben

Baumal,

MD, PhD

From the Departments of Pathology and Pediatrics, The Hospital for Sick Children, Toronto

ABSTRACT.

Persistent proteinuria, chronic renal failure, and focal segmental glomerulosclerosis developed in three children with solitary kidneys. Two of these children were born with unilateral kidneys. The third had bilateral reflux and underwent a unilateral nephrectomy and reim-plantation of the remaining ureter; persistent proteinuria developed 7 years later. It is postulated that

hyperperfu-sion of a critical number of glomeruli during childhood

may be the mechanism responsible for the production of

focal segmental glomerulosclerosis in these patients.

Pe-diatrics 1984;73:806-810; unilateral kidneys, focal

segmen-tal glomerulosclerosis.

Focal segmental glomerulosclerosis (FSGS) is the second most common cause of idiopathic nephrotic syndrome in childhood and often progresses to renal insufficiency.’ Although FSGS has been widely recognized in laboratory animals with uni-lateral kidneys,27 this association has only recently been reported in man.8 Kiprov et a!8 showed that FSGS was present in adults born with a solitary kidney but not in adults who had undergone uni-lateral nephrectomy. We report the development of proteinuria, chronic renal failure, and FSGS in three children with solitary kidneys.

CASE REPORTS

Case I

A 15-year-old male adolescent was found to have 2+

proteinuria during a routine presummer camp

examina-Received for publication June 1, 1983; accepted July 18, 1983. Reprint requests to (R.B.) Department of Pathology, The Hos-pital for Sick Children, 555 University Aye, Toronto, Ontario,

Canada M5G 1X8.

PEDIATRICS (ISSN 0031 4005). Copyright © 1984 by the

American Academy of Pediatrics.

tion when he was 1 1 years old. He was otherwise normal with height and weight at the 25th percentile. Investiga-tions revealed BUN of 23 mg/dL and serum creatinine

level was consistently about 1.6 mg/dL. The urine did not contain any blood or casts. A 24-hour urine showed

2.5 g of protein, and creatinine clearance was 64 mL/

min/1.73 m2. Values for serum electrolytes, lipids, and

proteins were normal. An intravenous pyelogram (IVP) showed that the kidney was in the right iliac fossa, but

there was no evidence of a left kidney on ultrasound examination. Cystourethogram indicated a normal

blad-der and urethra with no reflux. The patient has remained well without therapy, and at no time has he been hyper-tensive or edematous; however, the proteinuria has

per-sisted and there has been a slight reduction in growth

rate. At his most recent visit, the serum creatinine level

was 2.7 mg/dL, creatinine clearance was 19 mL/min/1.73

m’, and 24-hour urinary protein was 2.5 g. An open renal

biopsy was performed.

Case 2

An 8-year-old boy was admitted to the hospital on

numerous occasions from 6 months of age onward with pneumonia and asthma. During one of these stays (at 3#{189}

years of age), he was found to have proteinuria; there was

no hypertension. An IVP and ultrasound demonstrated an absent left kidney and compensatory hypertrophy of the right kidney. Cystoscopy showed a hemitrigone of the

bladder with a single ureteric orifice. There was no reflux

on a voiding cystourethrogram. Over the next 4 years, he

was followed by his family doctor; the boy’s urine was

normal except for persistent 2 to 4+ proteinuria. At no

time was edema present. Values for BUN and serum creatinine were in the normal range. The patient’s serum creatinine level was first noted to be elevated (1.3 mgI

dL) when he was 7 years old and he was referred to The

Hospital for Sick Children. Creatinine clearance was 43 mL/min/1.73 m2, and 24-hour urine protein was 0.75 g. Nine months later, the serum creatinine level was 1.6 mg/dL and creatinine clearance was 31 mL/min/1.73 m2.

(2)

Fig I. Renal biopsy from case 1, showing focal segmen- tubular atrophy and interstitial fibrosis. (hematoxylin-tal sclerotic lesions in glomerulus against background of phloxine-saffron, x140).

Case 3

MATERIALS

AND

METHODS

A 16-year-old male adolescent was first seen at 6 years

of age with a 1-week history of diarrhea and fever. Inves-tigations at that time revealed bilateral costovertebral

angle tenderness, pyuria, and Gram-negative bacilli in

the urine. There was no proteinuria. He was treated for pyelonephritis and dehydration, and the initial serum creatinine level of 3.8 fell to 1.5 mg/dL. IVP showed no function of the left kidney. Voiding cystourethrogram showed bilateral vesicoureteral reflux. Because of its poor function, the left kidney was surgically removed.

Histo-logic examination revealed renal dysplasia; no evidence

of FSGS was seen. Five months later, the patient’s re-maining ureter was reimplanted. At this time, creatinine clearance was 50 mL/min/1.73 m’. Over the next 7 years,

the patient remained asymptomatic; renal function was stable and no evidence of reflux, urethral obstruction,

edema, or proteinuria (checked twice annually) was ever

noted. He maintained normal height and weight (50th to

75th percentile) and was not hypertensive. Proteinurea (1 to 2+) with a rising serum creatinine level first

ap-peared when he was 13 years old. When last seen, his serum creatinine level was 2.7 mg/dL and a 24-hour urine sample contained 2.7 g of protein. An open renal biopsy was performed.

Open renal biopsies were performed on the three

patients and each specimen was divided into three

parts. The first was fixed in Helly’s solution and processed for routine paraffin sections; 3-j.m sec-tions were stained for light microscopy. The second

part was snap-frozen in liquid nitrogen, sectioned at 5 tm, and stained with fluorescein-conjugated rabbit antisera to immunoglobulins G, A, M, and C3. The third part was fixed in universal fixative

and processed for electron microscopy.

RESULTS

A!! three biopsies demonstrated similar features and are described together.

Light microscopy showed extensive areas of tu-bular atrophy, interstitial fibrosis, and a chronic interstitial inflammatory cell infiltrate (Fig 1). A spectrum of changes was seen in the g!omeru!i, ranging from normal (25%) to global sclerosis (25%

to 50%). The remaining glomeruli demonstrated

(3)

Renal biopsies were performed on three children with solitary kidneys, in order to ascertain whether

2.

(

Lomeru om case 3, showing segmental sclerotic 1

and hyaline deposit (arrowhead) (hematoxylin-phloxine-saffron, x350).

loop collapse, and foci of hyalinosis (Fig 2). The

scierosed segments were adherent to Bowman’s

capsule with overlying areas of prominent parieta! epithelium. In some cases, these changes were most marked at the vascular pole, but they were also seen in other portions of the glomeruli. Away from the

segmental lesions, glomerular capillary loops and

mesangial regions appeared normal. The affected glomeruli were often surrounded by fibrosis. None of the biopsies showed evidence of renal dysplasia or other congenital anomaly.

Immunofluorescence studies revealed focal seg-mental granular staining for 1gM and C3 in

gb-meruli, mainly in mesangia! regions.

Electron microscopy showed extensive fusion of foot processes of visceral epithe!ial cells and pseu-dovilbous transformation. Gbomerular capillary

basement membranes were wrinkled and thickened

in the areas of sclerosis. No electron-dense deposits were identified, but foam cells and osmiophi!ic

de-bris were occasionally found in a subendothelial

location.

DISCUSSION

their proteinuria and renal failure were a

conse-quence of FSGS. It is known that FSGS may be primary or secondary to a number of other diseases

including heroin abuse,9 segmental hypoplasia,’#{176} oligomeganephronia,1 Alport’s 12 and

re-flux nephropathy.’3 Recently, unilateral renal

agen-esis (ie, patients born with a solitary kidney) has

been described as a secondry cause of FSGS. In a

retrospective review of 586 renal biopsies and 9,200 autopsies, Kiprov et a!8 found five and two cases, respectively, of unilateral renal agenesis associated with FSGS. An eighth case was the father of one of the other seven cases. Seven of these cases were males; the youngest was 18 years old. In six cases,

terminal renal failure led to death. In one case, the patient was in chronic renal failure. No cases of FSGS were found in adults who had undergone

unilateral nephrectomy.

In our study, all three patients were male. They

were first seen with proteinuria at 3#{189}to 13 years

of age, with no evidence of a renal tubular defect.

Two ofthe patients were born with solitary kidneys; at no time did they have evidence of reflux and/or

pyebonephritis, yet both demonstrated FSGS on renal biopsy. The third patient was seen with reflux

(4)

poorly functioning kidney removed surgically; it

showed no evidence of FSGS. An antireflux proce-dure was performed on the remaining kidney.

Al-though the creatinine clearance was reduced at the time of ureteral reimplantation, there was no fur-ther reflux. Proteinuria

did

not appear until 7 years later, suggesting that FSGS did not develop until

this time.

What factor(s) may be responsible for the

initi-ation and progression of secondary FSGS, as seen in our three patients? Studies in animals27 have shown that the situation of a solitary kidney in

man can be simulated by performing renal ablation

experiments, which result in functional overload of

the remaining renal ti55ue.3’4’6”4 Although overall gbomerular filtration rate drops, the gbomerular fib-tration rate per individual nephron rises.3’4 This hyperperfusion per nephron leads to gbomerular

damage, heralded by proteinuria, and, in time,

FSGS which becomes well established within 2 to

50 weeks.3’4 The process is self-perpetuating,

be-cause with every glomerulus that becomes sclerotic, there is a further increase in perfusion of the re-maining nephrons. This may explain why renal injury occurring at one time progresses in the future to renal failure. Why the gbomerular lesion is

mi-tially segmental and begins in the juxtamedulbary region is not known. It has been postulated that

juxtamedullary gbomeruli have a higher filtration rate and thus are more susceptible than superficial

glomeruli to damage as a result of

hyperperfu-sion.2”5

An additional factor in the development of FSGS

has become clear from animal and human data. In uninephrectomized or /6 renal-ablated rats, several investigators’’9 observed that high protein diets

(up to 40% of calories) increased the severity of

FSGS, whereas a protein-restricted diet (6% of calories) minimized the development of FSGS.4’2#{176} Improved renal function was also noted in patients with progressive renal failure when their dietary

protein intake was reduced.2’ Studies have shown

that increasing the protein or amino acid content of the diet increases renal perfusion, perhaps via glucagon release.2#{176} This increase would aggravate

the hyperfusion per nephron already occurring

when renal mass is reduced.

What makes some children with one kidney

sus-ceptible to the development of FSGS and not others

is not clear. Although the incidence of solitary

kidneys in the general population is about 1/1,000,

the majority of affected individuals do not acquire renal disease. In addition, the effect of unilateral nephrectomy in adults is controversial. Some investigators have concluded that renal damage

does not occur after nephrectomy3’2224 whereas

others25’26 have detected subtle deterioration in

renal function, suggesting that such patients be followed closely for more obvious renal

abnormali-ties. One explanation that may account for the

progressive renal disease that ensues in some chil-dren with a solitary kidney is that there is a critical number of nephrons below which the kidney is at

risk to develop FSGS. If one is born with a solitary

kidney and appreciably less than 1 million neph-rons, perhaps the case in our first two patients, or if a kidney is removed from an individual and the remaining kidney has a significant number of

neph-rons destroyed (from reflux and/or pyebonephritis) as in our third patient, then in time, FSGS will

occur. Similarly, patients with oligomeganephronia or segmental hypoplasia may be at risk, while the

majority of patients born with solitary kidneys or

undergoing unilateral nephrectomy, yet who

pos-sess a full complement of 1 million functioning

nephrons would not be at risk. We believe that this mechanism may explain the development of FSGS

in our three patients.

It would appear that proteinuria and renal failure were a consequence of FSGS in patients 1 and 2, who were born with a solitary kidney, and in patient

3, who was left with a single kidney as a result of surgery. We feel that performance of renal biopsies was justified because it allowed us to determine that

FSGS was present, presumably as a result of

hy-perperfusion of the remaining nephrons.

Restric-tion ofprotein has been instituted in these children,

who had been receiving regular diets, because it has been shown that a high protein diet increases gb-merular filtration rate and would potentially aggra-vate the FSGS.2#{176}It is conceivable that restricting dietary protein early in life might be more beneficial to these patients than doing so after renal failure

has developed.

REFERENCES

1. Habib R, Kleinknecht C: The primary nephrotic syndrome in childhood: Classification and clinicopathologic study of 406 cases. Pathol Annu 1971;6:417-474

2. Grond J, Schilthius MS, Koudstaal J, et al: Mesangial

function and glomerular sclerosis in rata after unilateral

nephrectomy. Kidney

mt

1982;22:338-343

3. Hostetter TH, Olson JL, Rennke HG, et al: Hyperfiltration in remnant nephrons: A potentially adverse response to renal ablation. Am J Physiol 1981;241:F85-F93

4. Olson JL, Hostetter TH, Rennke HG, et al: Altered glomer-ular permselectivity and progressive sclerosis following

ex-treme ablation of renal mass. Kidney

mt

1982;22:112-126

5. Shea SM, Raskova J, Morrison AB: Ultrastructure of the

glomerular basement membrane of rats with proteinuria due

to subtotal nephrectomy: Localization of anionic sites by cationic probe molecules. Am J Pathol 1980;100:513-526 6. Shimamura T, Morrison AB: A progressive

glomeruloscle-rosis occurring in partial five-sixths nephrectomized rats.

Am J Pat/wI 1975;79:95-106

7. Striker GE, Nagle RB, Kohnen PW, et al: Response to unilateral nephrectomy in old rats. Arch Pat/wI

(5)

8. Kiprov DD, Colvin RB, McCluskey RT: Focal and segmental

glomerulosclerosis and proteinuria associated with

unilat-eral renal agenesis. Lab Invest 1982;46:275-281

9. Grishman E, Churg J: Focal glomerular sclerosis in ne-phrotic patients: An electron microscopic study of glomer-ular podocytes. Kidney

mt

1975;7:111-122

10. Habib R: Pathology ofrenal segmental corticopapillary

scar-ring in children with hypertension: The concept of

segmen-tal hypoplasia, in Hodson CJ, Kincaid-Smith P (eds): Reflux

Nephropathy. New York, Masson, 1979, pp 220-239

11. Bernstein J: Renal hypoplasia and dysplasia, in Edelmann

CM Jr (ed): Pediatric Kidney Disease. Boston, Little, Brown and Co, 1978, vol 2, pp 541-557

12. Gaboardi F, Edefonti A, Imbasciati E, et al: Alport’s

syn-drome (progressive hereditary nephritis). Clin Nephrol 1974;2:143-156

13. Kincaid-Smith P: Glomerular and vascular lesions in

chronic atrophic pyelonephritis and reflux nephropathy.

Adv Nephrol 1975;5:3-17

14. Elema JD, Koudstaal J, Lamberts HB, et al: Spontaneous glomerulosclerosis in the rat: Effect of nephrectomy and

irradiation of the contralateral kidney. Arch Pathol 1971;91:418-425

15. Couser WG, Stilmant MM: Mesangial lesions and focal glomerular sclerosis in the aging rat. Lab Invest

1975;33:491-501

16. Glasser RI, Velosa JA, Michael AF: Experimental model of

focal sclerosis. I. Relationship to protein excretion in amino-nucleoside nephrosis. Lab Invest 1977;36:519-526

17. Lalich JJ, Allen JR: Protein overload nephropathy in rats with unilateral nephrectomy. II. Ultrastructural study. Arch

Pat/wI 1971;91:372-382

18. Lalich JJ, Burkholder PM, Paik WCW: Protein overload nephropathy in rats with unilateral nephrectomy: A correl-ative light immunofluorescence and electron microscopical analysis. Arch Pathol 1975;99:72-79

19. Lalich JJ, Faith GC, Harding GE: Protein overload

nephrop-athy in rats subjected to unilateral nephrectomy. Arch Pa-thol 1970;89:548-559

20. Brenner BM, Meyer TW, Hostetter TH: Dietary protein intake and the progressive nature of kidney disease. N EngI

J Med 1982;307:652-659

21. Maschio G, Oldrizzi L, Tessitore N, et al: Effects of dietary protein and phosphorus restriction on the progression of

early renal failure. Kidney

mt

1982;22:371-376

22. Aperia A, Broberger 0, Wikstad I, et al: Renal growth and

function in patients nephrectomized in childhood. Acta Poe-diatr Scand 1977;66:185-192

23. Aperia A, Broberger 0, Wilton P: Renal functional

adapts-tion in the remnant kidney in patients with renal agenesis

and in patients nephrectomized in childhood. Acta Paediatr

Scand 1978;67:611-615

24. Ogden DA: Consequences of renal donation in man. Am J Kid Dis 1983;11:501-511

25. Goldszer RC, Hakim RM, Brenner BM: Longterm followup of renal function in kidney transplant donors. Presented at

the 16th Annual Meeting of the American Society of Ne-phrologists, Washington, DC, Dec 4-7, 1983

26. Delano BG, Lazar LL, Friedman EA: Hypertension, a late

consequence of kidney donation. Presented at the 16th

Annual Meeting of the American Society of Nephrologists,

Washington, DC, Dec 4-7, 1983

MEETING: BEHAVIORAL PEDIATRICS FOR THE PRACTITIONER

South Carolina Chapter, American Academy of Pediatrics, Annual Scientific Meeting, “Behavioral Pediatrics for the Practitioner.” Faculty: Ronald G. Barr, MDCM, FRCP(C), John Reinhart, MD, and Harold Jackson, MD. Meeting Site: Marriott’s Hilton Head Resort, Hilton Head Island, South Carolina. Meeting Date: August 10-11, 1984. Credit: AMA Category I and PREP, 7 Hours. For more information, contact:

Barbara Jean Blanks SC Chapter AAP

(6)

1984;73;806

Pediatrics

Paul S. Thorner, Gerald S. Arbus, David S. Celermajer and Reuben Baumal

Unilateral Kidney

Focal Segmental Glomerulosclerosis and Progressive Renal Failure Associated with a

Services

Updated Information &

http://pediatrics.aappublications.org/content/73/6/806

including high resolution figures, can be found at:

Permissions & Licensing

http://www.aappublications.org/site/misc/Permissions.xhtml

entirety can be found online at:

Information about reproducing this article in parts (figures, tables) or in its

Reprints

http://www.aappublications.org/site/misc/reprints.xhtml

(7)

1984;73;806

Pediatrics

Paul S. Thorner, Gerald S. Arbus, David S. Celermajer and Reuben Baumal

Unilateral Kidney

Focal Segmental Glomerulosclerosis and Progressive Renal Failure Associated with a

http://pediatrics.aappublications.org/content/73/6/806

the World Wide Web at:

The online version of this article, along with updated information and services, is located on

American Academy of Pediatrics. All rights reserved. Print ISSN: 1073-0397.

References

Related documents

IS adoption. The results of this study have implications for IS adoption in small businesses. First, the study highlights the importance of having innovative and IS-knowledgeable

Tanaka, An adaptive framework for multipath routing via maximally zone-disjoint shortest paths in ad hoc wireless networks with directional antenna, in:

Another important author Joseph MerianusKujur in his article titled :Development- induced displacement in Chhhatishgarh: A case study from tribal prospective discussed about the

The use of the term antisocial disorder dates back only to DSM-III in 1980, but many of central features of this disorder have long been labeled as Psychopathy or

The correlation results of this finding suggested that transparency, equity, fair distribution and consistency of reward system have positive effect on the

Repeated normal and reverse phase column chromatography of ethyl acetate fraction supported by Thin Layer Chromatography have led to the isolation of pure single compound..

Occupy Madison in Wiscon- sin, and Opportunity Village in Eugene recognize this- a keystone of their model is to connect villagers with housed residents in the larger community

The Journal of Sustainability Education is pleased to be planning a March 2020 special issue, “Educating for Water Resilience in the Context of Climate Crisis,” to mark