renal biopsy in patients aged 80 years and older

9
Renal Biopsy in Patients Aged 80 Years and Older Ramesh Nair, MD, Jane M. Bell, MD, and Patrick D. Walker, MD Background: Renal abnormalities discovered in the elderly have often been considered the result of aging, hypertensive changes, and so on. Recently, we noted an increase in renal biopsies among patients 80 years and older. This is a demographic subset with little or no previously reported clinicopathologic correlation between renal biopsy findings and clinical syndromes. Methods: We examined our files for all biopsies performed in patients 80 years and older and report 100 patients of a total of 3,227 biopsies (3.1%) from multiple referral centers. Results: Significant differences in the disease spectrum were found in the very elderly, not only compared with studies of adults and children, but also compared with studies of renal biopsies in the elderly. Crescentic glomerulonephritis was the most common diagnosis in patients aged 80 years and older. Although membranous glomerulopathy is the most common cause of idiopathic nephrotic syndrome in studies of the elderly (23% to 38%) and adults (35% to 40%), only 15% of our patients aged 80 years and older with idiopathic nephrotic syndrome had membranous nephropathy. Overall, at least 40 of 100 biopsies performed on the very elderly showed a renal condition that would benefit from therapeutic intervention, and the remaining biopsies provided at least prognostic information and/or ruled out a more severe condition, preventing potentially harmful empiric therapy. Conclusion: As the population ages, more elderly patients are undergoing diagnostic renal biopsies. This study emphasizes the variance between clinical presentation and expected diagnosis compared with actual biopsy findings in patients aged 80 years and older. Am J Kidney Dis 44:618-626. © 2004 by the National Kidney Foundation, Inc. INDEX WORDS: Aged; aged 80 years and older; needle biopsy; glomerulonephritis; hypertensive nephrosclerosis; kidney disease. M ANIFESTATIONS OF renal disease are being recognized increasingly in people aged 80 years and older as the number of people in this demographic subset continues to in- crease. 1 However, alterations in renal function and/or abnormalities in urinalysis results in this group may be attributed to aging or hypertensive changes, leading to little, if any, diagnostic evalu- ation and therapeutic intervention. Previous stud- ies of renal disease in older people essentially have been limited to those aged between 60 and 79 years (a group we refer to as the elderly). Importantly, these studies suggested that renal disease found in the elderly is treatable in as many as 50% of patients. 2-12 However, the lack of significant numbers of patients aged 80 years and older (a set we refer to as the very elderly) and the reluctance to subject the very elderly to such interventional procedures as renal biopsy has limited the examination of renal disease in this age group. Ethical issues concerning renal biopsy and therapeutic interventions in the insti- tutionalized very elderly were additional chal- lenges. We recently noted a marked increase in renal biopsies in the very elderly. This may be caused by the overall increase in longevity, as well as the increase in the general health of this group. It also may be related to the overall expectations of continuing an active and healthy lifestyle as we age. 13 Biopsies were performed for the usual renal syndromes, but the distribu- tion of renal biopsy findings was significantly different from patterns seen in children, adults, and the elderly. METHODS Patient Selection We reviewed our case files from March 1, 2001, through December 5, 2003, to identify all renal biopsies performed on individuals aged 80 years or older. One hundred two biopsies from 101 patients were identified of a total of 3,227 biopsies (3.2%) from multiple referral centers. Two biopsies were inadequate for diagnosis (2%), but 1 of these 2 patients underwent a successful repeated biopsy for a total of 100 unique individuals used for analysis in this report. For comparison, we evaluated 433 non–renal transplant biopsies in patients aged 66 to 79 years from the same period (13.4% of our total biopsies). After eliminating 20 cases that were inadequate for diagnosis (4.6%), 413 cases remained for this study. From Nephropathology Associates, Little Rock, AR. Received March 18, 2004; accepted in revised form May 28, 2004. Address reprint requests to Patrick D. Walker, MD, Nephropathology Associates, 10802 Executive Center Dr, Suite 111, Benton Bldg, Little Rock, AR 72211. E-mail: [email protected] © 2004 by the National Kidney Foundation, Inc. 0272-6386/04/4404-0006$30.00/0 doi:10.1053/j.ajkd.2004.05.044 American Journal of Kidney Diseases, Vol 44, No 4 (October), 2004: pp 618-626 618

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Page 1: Renal biopsy in patients aged 80 years and older

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Renal Biopsy in Patients Aged 80 Years and Older

Ramesh Nair, MD, Jane M. Bell, MD, and Patrick D. Walker, MD

Background: Renal abnormalities discovered in the elderly have often been considered the result of aging,ypertensive changes, and so on. Recently, we noted an increase in renal biopsies among patients 80 years andlder. This is a demographic subset with little or no previously reported clinicopathologic correlation between renaliopsy findings and clinical syndromes. Methods: We examined our files for all biopsies performed in patients 80ears and older and report 100 patients of a total of 3,227 biopsies (3.1%) from multiple referral centers. Results:ignificant differences in the disease spectrum were found in the very elderly, not only compared with studies ofdults and children, but also compared with studies of renal biopsies in the elderly. Crescentic glomerulonephritisas the most common diagnosis in patients aged 80 years and older. Although membranous glomerulopathy is theost common cause of idiopathic nephrotic syndrome in studies of the elderly (23% to 38%) and adults (35% to

0%), only 15% of our patients aged 80 years and older with idiopathic nephrotic syndrome had membranousephropathy. Overall, at least 40 of 100 biopsies performed on the very elderly showed a renal condition that wouldenefit from therapeutic intervention, and the remaining biopsies provided at least prognostic information and/oruled out a more severe condition, preventing potentially harmful empiric therapy. Conclusion: As the populationges, more elderly patients are undergoing diagnostic renal biopsies. This study emphasizes the variance betweenlinical presentation and expected diagnosis compared with actual biopsy findings in patients aged 80 years andlder. Am J Kidney Dis 44:618-626.2004 by the National Kidney Foundation, Inc.

NDEX WORDS: Aged; aged 80 years and older; needle biopsy; glomerulonephritis; hypertensive nephrosclerosis;idney disease.

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ANIFESTATIONS OF renal disease arebeing recognized increasingly in people

ged 80 years and older as the number of peoplen this demographic subset continues to in-rease.1 However, alterations in renal functionnd/or abnormalities in urinalysis results in thisroup may be attributed to aging or hypertensivehanges, leading to little, if any, diagnostic evalu-tion and therapeutic intervention. Previous stud-es of renal disease in older people essentiallyave been limited to those aged between 60 and9 years (a group we refer to as the elderly).mportantly, these studies suggested that renalisease found in the elderly is treatable in asany as 50% of patients.2-12 However, the lack

f significant numbers of patients aged 80 yearsnd older (a set we refer to as the very elderly)nd the reluctance to subject the very elderly touch interventional procedures as renal biopsyas limited the examination of renal disease in

From Nephropathology Associates, Little Rock, AR.Received March 18, 2004; accepted in revised form May

8, 2004.Address reprint requests to Patrick D. Walker, MD,

ephropathology Associates, 10802 Executive Center Dr,uite 111, Benton Bldg, Little Rock, AR 72211. E-mail:[email protected]© 2004 by the National Kidney Foundation, Inc.0272-6386/04/4404-0006$30.00/0

sdoi:10.1053/j.ajkd.2004.05.044

American Journal of K18

his age group. Ethical issues concerning renaliopsy and therapeutic interventions in the insti-utionalized very elderly were additional chal-enges.

We recently noted a marked increase inenal biopsies in the very elderly. This may beaused by the overall increase in longevity, asell as the increase in the general health of thisroup. It also may be related to the overallxpectations of continuing an active and healthyifestyle as we age.13 Biopsies were performedor the usual renal syndromes, but the distribu-ion of renal biopsy findings was significantlyifferent from patterns seen in children, adults,nd the elderly.

METHODS

atient SelectionWe reviewed our case files from March 1, 2001, through

ecember 5, 2003, to identify all renal biopsies performedn individuals aged 80 years or older. One hundred twoiopsies from 101 patients were identified of a total of 3,227iopsies (3.2%) from multiple referral centers. Two biopsiesere inadequate for diagnosis (2%), but 1 of these 2 patientsnderwent a successful repeated biopsy for a total of 100nique individuals used for analysis in this report. Foromparison, we evaluated 433 non–renal transplant biopsiesn patients aged 66 to 79 years from the same period (13.4%f our total biopsies). After eliminating 20 cases that werenadequate for diagnosis (4.6%), 413 cases remained for this

tudy.

idney Diseases, Vol 44, No 4 (October), 2004: pp 618-626

Page 2: Renal biopsy in patients aged 80 years and older

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RENAL BIOPSY IN PATIENTS AGED 80 AND OLDER 619

linical SyndromesClinical presentations were grouped as follows: nephrotic

yndrome, acute nephritic syndrome, acute renal failure,apidly progressive renal failure, chronic renal failure, andsymptomatic urinary abnormalities (Table 1).14,15 Clinicalnformation was gathered from data sheets provided with theenal biopsy and from routine follow-up telephone conversa-ions with the clinician regarding renal biopsy results. Avail-ble data included pertinent clinical history, serum creati-ine concentration, urinalysis results, 24-hour urine proteinxcretion, urine and/or serum protein electrophoresis, pres-nce of antineutrophil cytoplasmic antibody, and presence ofnti–glomerular basement membrane antibody, among oth-rs. To determine morbidity and mortality related to theiopsy procedure, a follow-up questionnaire was sent forach patient. Referring nephrologists were asked if there hadeen “death due to biopsy,” “complications” (defined asleeding requiring transfusion and/or surgical intervention,erinephric hematoma, formation of an arteriovenous fis-ula, and so on), or “no complications” (defined as noostbiopsy problems, mild postbiopsy pain, hematuria notequiring transfusion, and so on).

enal Histological EvaluationRenal biopsy specimens were processed for light, immu-

ofluorescence, and electron microscopy. For light micros-opy, 2- to 3-�m thick serial sections of formalin-fixedaraffin-embedded tissue were stained for hematoxylin andosin, periodic acid–Schiff reaction, and Jones methenamineilver or Masson trichrome stains. When indicated, Congoed and thioflavin-T stains for amyloid also were performed.or immunofluorescence, 4- to 5-�m thick serial cryostatections were stained with fluoresceinated antisera specificor immunoglobulin G (IgG), IgA, IgM, C3, C4, C1q,brinogen, albumin, and � and � light chains. For electronicroscopy, tissue was fixed in formalin, postfixed in os-ium tetroxide, and embedded in epoxy resin, and thin

ections were stained with uranyl acetate. All renal biopsyaterials were reviewed without knowledge of clinical infor-

Table 1. Clinic

Syndrome

ephrotic syndrome Proh

cute nephritic syndrome Redteo

apidly progressive renal failure A sum

cute renal failure A sus

hronic renal failure A slsymptomatic urinary abnormalities Isol

h

Data derived from Alam and Shah14 and Walker and Sha

ation. m

tatisticsThe distribution of renal biopsy and clinical findings

mong various age groups was compared using Pearson’shi-square test. Results are considered significant for P lesshan 0.05.

RESULTS

Average age of very elderly patients was 83.3ears, with a range of 80 to 91 years (Fig 1A);here were 48 men and 52 women (man-womanatio, 0.92/1.0). Average age of elderly patientsas 71.5 years, with a range of 66 to 79 years

Fig 1B); there were 246 men and 165 women inhis group (man-woman ratio, 1.49/1.0). Data forhe very elderly and elderly are from our labora-ory and are compared with renal biopsies inhildren (defined as �15 years; boy-girl ratio,.2 to 1; mean age, 9 years; range, 1 to 14 years)nd adults (defined as 15 to 65 years; male-emale ratio, 1.5 to 1; mean age, 41 years; range,5 to 64 years) derived from the Spanish Regis-ry of Glomerulonephritis.16 Data also are com-ared with a renal biopsy series from the Univer-ity of North Carolina Nephropathologyaboratory that includes patients of all ages.17

hese groups were chosen because they were thelosest approximation to our data from the ratherimited recent literature regarding renal biopsyeries.

ndications for Renal Biopsy

Percentages of patients undergoing renal bi-psy for various renal syndromes are listed inable 2. Nephrotic syndrome was the most com-

al Syndromes

Features

with protein � 3.5 g/24 h/1.73 m2 with or without edema,uminemia, hyperlipidemia, or hyperlipiduriacell casts and/or dysmorphic red cells on urinalysislly associated with acute renal failure with or without new-pertensiondecline in renal function developing over weeks to

decline in renal function developing in days to weekst to cause retention of nitrogenous wasteline in renal function developing over months to yearsild proteinuria with protein � 2.0 g/24 h/1.73 m2 oria with or without mild proteinuria

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Page 3: Renal biopsy in patients aged 80 years and older

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xcept the elderly (nephrotic syndrome, 33%;cute renal failure, 41%; Table 2). However, inhe very elderly and elderly, nephrotic syndromes significantly less often the indication for renaliopsy compared with children or the Universityf North Carolina Nephropathology Laboratoryroup.Acute nephritic syndrome is a significantlyore common indication for renal biopsy among

he very elderly compared with all other groups.his is not surprising when compared with a

enal biopsy series in children because most

Fig 1. Number of patients aged (A)

Table 2. Presentat

All*(n � 7,257)

ephrotic syndrome 42NS

cute nephritic syndrome 15NS

apidly progressive renal failure 5NS

symptomatic urinary abnormalities 9�0.01

cute renal failure 5�0.001

hronic renal failure 8�0.01

ther 16*

NOTE. Data are expressed as percentage of total.Abbreviations: NA; not available; NS; not significant.*University of North Carolina Nephropathology Laborat

ther diseases (3%), no pathological diagnosis (2%), nonsp†Spanish Registry of Glomerulonephritis16; children, age

f children and 4% of adults in this report underwent a rena

‡Nephropathology Associates Laboratory; elderly, aged 66 to 7

hildren with acute nephritic syndrome arehought to have poststreptococcal glomerulone-hritis and do not require a renal biopsy.18 How-ver, there is a decided trend toward renal biopsyor this syndrome as the population under exami-ation ages (elderly, 12%; very elderly, 20%).Rapidly progressive renal failure was not a

ategory used in the Spanish Registry of Glomer-lonephritis. This complicated exact comparisonecause patients we refer to as having rapidlyrogressive renal failure are included amongther syndromes in the Spanish Registry. How-

rs and older and (B) 66 to 79 years.

Renal Syndromes

ren†473)

Adults†(n � 3,079)

Elderly‡(n � 413)

Very Elderly‡(n � 100)

35 33 33S NS NS

4 12 20001 �0.001 �0.03A NA 4 6

NS35 1 1

001 �0.001 NS10 41 23

001 �0.001 �0.00112 9 17

001 NS �0.0014† 0 0

the remaining 16% of their biopsies were categorized asbnormalities (5%), and inadequate for diagnosis (6%).

er than 15 years; adults, aged 15 to 65 years. One percentfor hypertension.

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Page 4: Renal biopsy in patients aged 80 years and older

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RENAL BIOPSY IN PATIENTS AGED 80 AND OLDER 621

ver, it seems most likely that patients in thisategory would have been placed in the acuteephritic syndrome group. Thus, if removed fromhat category, differences between the elderlynd very elderly versus children and adults woulde accentuated further in regard to the incidencef biopsy for acute nephritic syndrome.Renal biopsy for asymptomatic urinary abnor-alities was significantly lower among the el-

erly and very elderly compared with the otherroups. This seems appropriate given the rela-ively benign nature of diseases likely to beound by biopsy in this syndrome in older popu-ations.

Acute renal failure is a significantly moreommon reason for biopsy among those olderhan 65 years compared with children, adults, orll. This may be caused by an actual increasedrequency of acute renal failure in the elderly andery elderly and/or the perceived need for a rapidiagnosis in these populations.There are multiple reasons to perform biopsy

n a patient with chronic renal failure, includinghe need for prognostic information, possibilityf discovering a potentially treatable condition,nd utility of a firm diagnosis if renal transplanta-ion is needed. In certain cases among the verylderly, biopsy was performed in the small hopef discovery of a treatable condition because theatient did not desire dialysis therapy.

enal Biopsy Diagnoses

Changes consistent with benign nephrosclero-is were found in only 35 of 100 very elderlyatients (35%). Diagnoses in the other 65 pa-ients, expressed as percentage of the total num-er of biopsies (n � 100), were as follows:auci-immune crescentic glomerulonephritis19%), focal segmental glomerulosclerosis (7%),inimal change disease (6%), acute interstitial

ephritis (5%), diabetic nephropathy (4%), acuteubular necrosis (3%), amyloidosis (3%), mem-ranous glomerulopathy (2%), and others (16%).Renal biopsy diagnoses in the very elderly

rranged by clinical presentation are listed inable 3. Overall, benign nephrosclerosis was theost common diagnosis rendered for the very

lderly with nephrotic syndrome. This perhaps isurprising given that hypertensive, arteriosclero-is, or aging-associated nephrosclerosis gener-

lly is thought to produce only non–nephrotic- n

ange proteinuria.19 In each of these cases, theossibility of minimal change disease overlyingenign nephrosclerosis was ruled out. This wasased on both clinical and pathological factors.linical features against the diagnosis of mini-al change disease include time to onset of

ephrotic syndrome (gradual instead of rapid)nd the absence of secondary conditions associ-ted with minimal change disease (eg, leukemia/ymphoma, nonsteroidal anti-inflammatorygents20). The usual pathological finding of ex-ensive effacement of the foot process seen bylectron microscopy in cases of minimal changeisease was not found in these cases. One caveatemains in that focal segmental glomerulosclero-is cannot be ruled out. Among patients withdiopathic nephrotic syndrome, there were markedifferences between the very elderly and elderlynd adult populations. In Table 4, the subset ofll patients with the 3 main forms of idiopathicephrotic syndrome (minimal change disease,ocal segmental glomerulosclerosis, and membra-ous nephropathy) are compared by age. In theery elderly, the pattern is much more similar tohat seen in children than in either adults or thelderly, with minimal change disease more com-on than focal segmental glomerulosclerosis

nd focal segmental glomerulosclerosis moreommon than membranous glomerulopathy inhis population.

Very elderly patients with acute nephritic syn-rome most commonly were found to have cres-entic glomerulonephritis (13 of 20 patients withhis syndrome). Similarly, 25 of 37 elderly pa-ients with acute nephritic syndrome had crescen-ic glomerulonephritis. These cases likely are notruly acute nephritic syndrome (renal failure de-eloping in days to weeks), but rather are rapidlyrogressive renal failure (renal failure develop-ng in weeks to months). It often is difficult toccurately determine the time to renal failure inlder patients. Neither postinfectious glomerulo-ephritis nor lupus nephritis, the 2 most commonauses of acute nephritic syndrome in childrennd adults, was found in very elderly patients.ostinfectious glomerulonephritis also was noteen in the elderly population with acute ne-hritic syndrome, although 6 of 37 patients hadupus nephritis.

Benign nephrosclerosis presented as acute re-

al failure in both the elderly and very elderly.
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NAIR, BELL, AND WALKER622

lso, 2 of 23 very elderly patients and 21 of 169lderly patients with acute renal failure had cres-entic glomerulonephritis. In both cases, thisikely reflects the difficulty of accurate assign-ent to clinical syndromes in these populations.

Table 3. Renal Biopsy Dia

Clinical Presentation

ephrotic syndromeMinimal chanFocal segmenMembranousAmyloidosisBenign nephrDiabetic NephIgA nephropaOther

cute nephritic syndromeCrescentic GNCrescentic GNGranulomatoIgA nephropaMPGN ICryoglobulineCholesterol eLupus nephritNonspecific c

cute renal failureAcute postinfeAcute interstitAcute tubularIgA nephropaLight-chain caLight-chain deAmyloidosisBenign nephrDiabetic nephCrescentic GNCrescentic GNCholesterol eThrombotic mOther

apidly progressive renal failureCrescentic GNCrescentic GNCrescentic GNLight-chain caFocal segmenOther

hronic renal failureBenign nephrDiabetic nephFocal segmenAmyloidosisOther

cute interstitial nephritis was common in both g

he elderly and very elderly age groups withcute renal failure.

Percentages of patients with rapidly progres-ive renal failure were approximately the samemong the elderly, very elderly, and all age

s by Clinical Presentation

sisVery Elderly

(n � 100)Elderly

(n � 413)

33 33ase 6 4merulosclerosis 5 4pathy 2 7

3 3sis 14 8y 1 5

1 01 2

20 12I anti-GBM 1 0*III pauci-immune 12 6ulitis 1 0

2 01 2

pe I 1 01 00 1

/Other 1 323 41

GN 0 1hritis 5 6is 2 1

2 0*hropathy 3 2n disease 1 0*

0 1sis 5 12y 2 2I anti-GBM 0 0*III pauci-immune 2 5

1 3giopathy 0 1

0 7†6 4

III pauci-immune 2 1I anti-GBM 1 0*loidosis 1 0hropathy 1 0merulosclerosis 1 0

0 3‡17 9

sis 15 6y 1 1merulosclerosis 1 0§

0 10 1§

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Diagno

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roups in the North Carolina series (Table 2).

Page 6: Renal biopsy in patients aged 80 years and older

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RENAL BIOPSY IN PATIENTS AGED 80 AND OLDER 623

owever, only 50% of very elderly patients and5% of elderly patients with this syndrome hadrescentic glomerulonephritis (Table 3). Lighthain cast nephropathy, fibrillary glomerulopa-hy, and amyloidosis were among the diagnosesound in patients older than 65 years with rapidlyrogressive renal failure.Chronic renal failure was the indication for

enal biopsy in 17% of very elderly patients and% of elderly patients. Benign nephrosclerosisas found in 15 of 17 very elderly patients, withiabetic nephropathy and focal segmental glomer-losclerosis in the other 2 patients. However, in

Table 3

Clinical Presentation

symptomatic urinary abnormalitiesBenign nephrThin GBM synOther

NOTE. Data are expressed as percentage of total biopsieAbbreviations: GN, glomerulonephritis; GBM, glome

lomerulonephritis.*Zero percent; but 1 or 2 patients.†Seven percent of patients with acute renal failure, inc

lomerulosclerosis, 2 patients; focal proliferative glomeruloatients; Henoch-Schönlein purpura, 1 patient; membranoucute pyelonephritis, 1 patient; type I cryoglobulinemia, 1 p‡Three indicates 3.34% of patients with rapidly progres

myloidosis, 2 patients; acute tubular necrosis, 1 patient; cgA nephropathy, 1 patient; diabetic nephropathy, 1 patientpatient.§One indicates 1.45% of patients with chronic renal failu

lomerulosclerosis, 1 patient; cholesterol emboli, 1 patient;is, type III pauci-immune, 1 patient; and lupus nephritis, 1 p

Table 4. Idiopath

Children*

inimal change disease 58NS

ocal segmental glomerulosclerosis 36NS

embranous nephropathy 6�0.001

NOTE. Data are expressed as percentage of the total wihe very elderly. Very elderly versus adults and elderlephropathy; very elderly versus children, P � NS for minery elderly versus children, adults, and elderly for focal seAbbreviation: NS, not significant.*From the Spanish Registry of Glomerulonephritis16; chil

†From Nephropathology Associates Laboratory; elderly, aged 6

he elderly population, 12 of 37 patients withhronic renal failure had conditions other thanenign nephrosclerosis, often with therapeuticotential, including crescentic glomerulonephri-is, granulomatous vasculitis, and acute intersti-ial nephritis (Table 3).

Elderly patients with asymptomatic urinarybnormalities were found to have thin basementembrane syndrome, IgA nephropathy, and be-

ign recurrent hematuria in 4 of 7 biopsies. Theemaining elderly patients and the 1 very elderlyatient with this syndrome had benign nephroscle-osis.

tinued

sisVery Elderly

(n � 100)Elderly

(n � 413)

1 3sis 1 1

0 10 1

basement membrane; MPGN, membranoproliferative

polyethylene glycol toxicity, 2 patients; focal segmentalis, 1 patient; pseudodiabetic nodular glomerulosclerosis, 4erulopathy, 1 patient; granulomatous vasculitis, 1 patient;

and no changes, 5 patients.nal failure, including benign nephrosclerosis, 5 patients;rol emboli, 1 patient; acute interstitial nephritis, 1 patient;cryoglobulinemia, 1 patient; and fibrillary glomerulopathy,

ding acute interstitial nephritis, 1 patient; focal segmentallomatous vasculitis, 1 patient; crescentic glomerulonephri-

hrotic Syndrome

Adults* Elderly† Very Elderly†

26 20 46�0.001 �0.00139 39 38

NS NS35 41 15�0.001 �0.001

athic nephrotic syndrome in each group. P compared with0.001 for minimal change disease and membranous

ange disease, P � 0.001 for membranous nephropathy;l glomerulosclerosis, P � NS.

ounger than 15 years; adults, aged 15 to 65 years.

. Con

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6 to 79 years; very elderly, age 80 years or older.
Page 7: Renal biopsy in patients aged 80 years and older

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The most common renal biopsy diagnosesompared across various ages are listed in Table. Crescentic glomerulonephritis was the diagno-is in 19% of the very elderly compared with2% of the elderly and 5% of the adult popula-ion. Conversely, membranous glomerulopathyccurred in only 2% of the very elderly, almostdentical to the 3% incidence in children andignificantly less than that in both the adult andlderly populations. Lupus nephritis was noteen in any very elderly patient.

Several unusual and unexpected diagnosesere found in our 100 biopsies of patients aged0 years and older, including a patient with typemonoclonal cryoglobulinemia. This biopsy led

o a detailed workup showing unsuspected recur-ence of a small B-cell lymphoma that had beenn remission for more than 2 years. Also, 4lasma cell dyscrasias were discovered after light-hain–associated renal disease (2 cases of light-hain cast nephropathy, 1 case each of light-hain deposition disease and amyloidosis) wasiagnosed on renal biopsy, although 1 had aositive urine protein electrophoresis result athe time of the biopsy.

omplications

The majority of serious post–renal biopsy com-

Table 5. Most

Childr

rescentic glomerulonephritis 2�0.0

ocal segmental glomerulosclerosis 15�0.0

inimal change disease 24�0.0

gA nephropathy 20�0.0

myloid 0NS

embranous glomerulopathy 3NS

embranoproliferative glomerulonephritis 3NS

ystemic lupus erythematosus 7�0.0

NOTE. Data are expressed as percentage of all diagnoseAbbreviation: NS, not significant.*Spanish Registry of Glomerulonephritis16; children, you†Nephropathology Associates Laboratory; elderly, aged

lications (including death, surgical interven- g

ion, and transfusion) occur in the first 18 to 24ours after biopsy.21 There were no deaths orajor complications reported immediately after

iopsy. The follow-up questionnaire was devel-ped to determine whether there had been lateeaths or other significant complications. Thereere replies for 47 of 100 patients. One of the 47atients developed a perinephric hematoma, butid not require surgical intervention or transfu-ion. Another patient had significant postopera-ive bleeding requiring transfusion and intra-rterial coil placement. No death caused by biopsynd no other significant complications were re-orted. One patient with crescentic glomerulone-hritis went to end stage, but declined dialysisherapy and died. Two patients died of unrelatedauses: 1 patient at 6 months and another patientt 8 months post renal biopsy.

DISCUSSION

This is the first report of renal biopsy results inlarge number of patients aged 80 years and

lder (the very elderly). Significant differencesn the disease spectrum were found, not onlyompared with studies of adults and chil-ren,16,22,23 but also compared with studies ofenal biopsies in the elderly.4,6-8,24,25 Crescentic

on Diagnoses

Adults* Elderly† Very Elderly†

5 13 19�0.001 NS11 5 7

NS NS7 4 6NS NS

17 1 4�0.05 �0.01

3 4 3NS NS

10 7 2�0.02 0.059 NS

5 1 1NS NS

12 3 0�0.001 NS

e in the given age group. P compared with the very elderly.

an 15 years; adults, aged 15 to 65 years.9 years; very elderly, 80 years or older.

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lomerulonephritis was the most common diag-

Page 8: Renal biopsy in patients aged 80 years and older

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RENAL BIOPSY IN PATIENTS AGED 80 AND OLDER 625

osis (19%) in patients 80 years and older com-ared with 5% in adults and 13% in the elderly.In the very elderly, the distribution of diseases

ssociated with nephrotic syndrome was mark-dly different from what had been expected.lthough membranous glomerulopathy is theost common cause of idiopathic nephrotic syn-

rome in studies of the elderly (23% to 38%) anddults (35% to 40%), only 15% of our patientsged 80 years and older with idiopathic ne-hrotic syndrome had membranous nephropathy.inimal change disease accounted for 46%, and

ocal segmental glomerulosclerosis 38%, in ourery elderly patients, a distribution much moreike that found in children than in either adults orhe elderly. Benign nephrosclerosis was the diag-osis in 14 of 33 patients with nephrotic syn-rome despite the prevailing thought that benignephrosclerosis is associated with only mild pro-einuria, usually less than nephrotic range.19

In the very elderly, acute nephritic syndromeas associated most frequently with crescenticlomerulonephritis, rather than postinfectious glo-erulonephritis, the disease group usually asso-

iated with this syndrome in children and adults.iven that the clinical difference between rap-

dly progressive renal failure and acute nephriticyndrome is based on time to renal insufficiency,his difference may reflect the difficulty determin-ng the onset of symptoms in the very elderly.arly manifestations of crescentic glomerulone-hritis may be milder in the very elderly and maye ignored. In addition, baseline renal functionay not be known, leading to additional diffi-

ulty in accurate syndrome assignment. Still, thiss critically important given the differential diag-osis, treatment, and prognosis of diseases asso-iated with these 2 syndromes.

Similarly, acute renal failure may elude accu-ate clinical assessment in the very elderly. Thiss supported by the finding of benign nephroscle-osis as the sole lesion in almost a third ofatients in this category. These cases likely repre-ent a slow and undetected decline in renalunction that, on acute discovery of poor renalunction, leads to biopsy. Importantly, poten-ially reversible acute interstitial nephritis wasiagnosed in approximately half the patients withcute renal failure.

Only 4 patients presented with rapidly progres-

ive glomerulonephritis among the very elderly. p

gain, this likely represents the difficulty ineneral of assigning patients to this syndrome, aroblem that may be exaggerated in the verylderly. Still, 2 of the 4 patients with rapidlyrogressive glomerulonephritis did not have cres-entic glomerulonephritis. One patient had light-hain cast nephropathy and the other patient hadocal segmental glomerulosclerosis, both entitiesith markedly different treatment and outcome

rom each other and crescentic glomerulonephri-is.

Overall, at least 40 of the 100 biopsieserformed on the very elderly showed a renalondition that would benefit from therapeuticntervention (eg, pauci-immune crescentic glo-erulonephritis, minimal change disease, mem-

ranous nephropathy, severe acute interstitial ne-hritis).2,11,26-28 The remaining biopsies providedt least prognostic information and/or ruled out aore severe condition, preventing potentially

armful empiric therapy. The risk for complica-ions in this series was no greater than that forther age groups, and the potential benefits weres high.21,29,30

There is ongoing debate regarding the impactf the aging of the population on health carexpenditures,31-33 and serious ethical questionsurrounding this issue are being discussed.34,35

n the area of renal disease, vigorous discussionontinues about the initiation of dialysis therapyor elderly patients with the attendant risk fordditional disability, other medical complica-ions, and overall costs.36 However, it appearshat for the most part, patients are choosingialysis rather than certain death from end-stageenal disease. In the United States, patients beingdded to the dialysis roles at the greatest rate arehose aged 75 years and older.37 For patients athe end of the age spectrum, this study empha-izes the increasing use of renal biopsy for cor-ect diagnosis, leading to a more directed thera-eutic approach.

REFERENCES

1. Freid VM, Prager K, MacKay AP, et al: Health, Unitedtates, 2003: With Chartbook on Trends in the Health ofmericans. Hyattsville, MD, National Center for Healthtatistics, 20032. Donadio JV: Treatment and clinical outcome of glomer-

lonephritis in the elderly. Contrib Nephrol 105:49-57, 19933. Bergesio F, Bertoni E, Bandini S, et al: Changing

atterns of glomerulonephritis in the elderly: A change of

Page 9: Renal biopsy in patients aged 80 years and older

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NAIR, BELL, AND WALKER626

revalence or a different approach. Contrib Nephrol05:75-80, 19934. Davison AM, Johnston PA: Idiopathic glomerulonephri-

is in the elderly. Contrib Nephrol 105:38-48, 19935. Colombo V, Confalonieri R, Minola E, et al: Renal

iopsies in the elderly. Contrib Nephrol 105:102-106, 19936. Glassock RJ: Glomerular disease in the elderly popula-

ion. Geriatr Nephrol Urol 8:149-154, 19987. Preston RA, Stemmer CL, Materson BJ, et al: Renal

iopsy in patients 65 years of age or older. J Am Geriatr Soc8:669-674, 19908. Modesto-Segonds A, Ah-Soune MF, Durand D, et al:

enal biopsy in the elderly. Am J Nephrol 13:27-34, 19939. Davison AM: Renal disease in the elderly. Nephron

0:6-16, 199810. Brown WW, Davis BB, Spry LA, et al: Aging and the

idney. Arch Intern Med 146:1790-1796, 198611. Moran D, Korzets Z, Bernheim J, et al: Is renal

iopsy justified for the diagnosis and management of theephrotic syndrome in the elderly. Gerontology 39:49-54,99312. Cameron JS: Nephrotic syndrome in the elderly.

emin Nephrol 16:318-329, 199613. Campion EW: Aging better. N Engl J Med 338:1064-

066, 199814. Alam MG, Shah SV: Approach to the patient with

enal disease, in Andreoli TE, Carpenter CCJ, Griggs RC, etl (eds): Cecil Essentials of Medicine. Philadelphia, PA,aunders, 2004, pp 237-24215. Walker PD, Shah SV: Glomerular diseases, in An-

reoli TE, Carpenter CCJ, Griggs RC, et al (eds): Cecilssentials of Medicine. Philadelphia, PA, Saunders, 2004,p 259-27216. Rivera F, Lopez-Gomez JM, Perez-Garcia R: Fre-

uency of renal pathology in Spain 1994-1999. Nephrol Dialransplant 17:1594-1602, 200217. Jennette JC, Falk RA: Glomerular clinicopathologic

yndromes, in Greenberg A, Cheung AK, Coffman TM, et aleds): National Kidney Foundation Nephrology Primer. Saniego, CA, Academic, 1998, pp 127-14018. Silva FG, Hogg RJ: Glomerular lesions associated

ith the acute nephritic syndrome and hematuria. Seminiagn Pathol 5:4-38, 198819. Mujais SK, Emmanouel DS, Kasinath GS, et al:arked proteinuria in hypertensive nephrosclerosis. Am Jephrol 5:190-195, 198520. Glassock RJ: Secondary minimal change disease.

ephrol Dial Transplant 18:Svi52-Svi58, 2003 (suppl 6) (

21. Whittier WL, Korbet SM: Timing of complications inercutaneous renal biopsy. J Am Soc Nephrol 15:142-147,00422. Orth SR, Ritz E: The nephrotic syndrome. N Engl

Med 338:1202-1211, 199823. Cattran DC: Idiopathic membranous glomerulonephri-

is. Kidney Int 59:1983-1994, 200124. Levison SP: Renal disease in the elderly: The role of

he renal biopsy. Am J Kidney Dis 16:300-306, 199025. Zech PY, Colon S, Pointet PH, et al: The nephrotic

yndrome in adults over 60: Etiology, evolution and treat-ent in 76 cases. Clin Nephrol 17:232-236, 198226. Furci L, Medici G, Baraldi A, et al: Rapidly progres-

ive glomerulonephritis in the elderly: Long-term results.ontrib Nephrol 105:98-101, 199327. Palmieri PF, Bonomini M, Di Mizio G, et al: Ne-

hrotic syndrome in the elderly: A retrospective study interoid-treated patients. Contrib Nephrol 105:58-64, 1993

28. Haas M, Spargo BH, Wit EJ, et al: Etiologies andutcome of acute renal insufficiency in older adults: A renaliopsy study of 259 cases. Am J Kidney Dis 35:433-447,00029. Parrish AE: Complications of percutaneous renal bi-

psy: A review of 37 years’ experience. Clin Nephrol 38:135-41, 1992

30. Kim D, Kim H, Shin G, et al: A randomized, prospec-ive, comparative study of manual and automated renaliopsies. Am J Kidney Dis 32:426-431, 199831. Lubitz J, Cai L, Kramarow E, et al: Health, life expect-

ncy, and health care spending among the elderly. N EnglMed 349:048-1055, 200332. Vita AJ, Terry RB, Hubert HB, et al: Aging, health risks,

nd cumulative disability. N Engl J Med 338:1035-1041, 199833. Campion EW: The oldest old. N Engl J Med 330:1819-

820, 199434. Levinsky NG: The purpose of advance medical plan-

ing—Autonomy for patients or limitation of care? N EnglMed 335:741-743, 199635. Callahan D: Controlling the costs of health care for

he elderly—Fair means and foul. N Engl J Med 335:743-46, 199636. Moss AH: Too many patients who are too sick to

enefit start chronic dialysis. Nephrologists need to learn tojust say no.” Am J Kidney Dis 41:723-732, 2003

37. US Renal Data System: Excerpts from the USRDS003 Annual Data Report: Atlas of end-stage renal disease inhe United States. Am J Kidney Dis 42:S13-S24, 2003

suppl 5)