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Maintenance dialysis for diabetic nephropathy with uremia
J Chron Dis 1975, Vol. 28, pp. 365-374. Pergamon Press. Printed in Great Britain
MAINTENANCE DIALYSIS FOR DIABETIC NEPHROPATHY WITH UREMIA* C. HUANG,? F. DEL GRECO, P. IVANOVICH,F.
A. KRuMLovsKY, J. ROGUSKA,N. M. SIMONand J. HANO
Department of Medicine, Northwestern University Medical School, Northwestern Memorial Hospital, and V.A. Research Hospital, Chicago, Illinois 60611, U.S.A. (Received 7 August 1974)
NOTABLEsuccesses have been achieved with maintenance dialysis for nondiabetic uremic patients, and survival rates of 83.7 and 95.6 per cent at 1 yr have been reported [l-6]. By contrast, the value of long-term dialysis for treating patients with diabetic nephropathy and uremia is still in doubt. The pertinent available evidence is conflicting, and rates of rehabilitation, morbidity and mortality vary greatly [7-171. Since the availability of maintenance dialysis is being greatly expanded, an increasing number of diabetics with uremia is likely to be placed on such therapy. It is, therefore, of considerable practical importance to evaluate the experience available to date. Between January, 1963 and December, 1973, 150 patients with chronic uremia have been placed on maintenance dialysis at our center. The purpose of this report is to describe 14 of these patients who had uremia caused by diabetic nephropathy. MATERIALS
AND
METHODS
The clinical findings on admission are summarized in Table 1. There were 12 men and 2 women, ranging in age from 28 to 61 yr. The patients had known diabetes mellitus for 7-29 yr. Six patients had had diabetes since childhood, while in eight the disease was of adult onset. Hypertension was present in nine patients, and features of circulatory congestion with heart failure were noted in 11. All patients had edema, with anasarca in seven. Two patients were partially blind, and the remainder had varying degrees of retinopathy. Peripheral neuropathy, as evidenced by decreased deep tendon reflexes and nerve conduction velocity studies, was present in 13 cases, and diminished or absent peripheral pulses were found in 12. The initial laboratory data are listed in Table 2. All patients had anemia of varying degree. Mean blood urea nitrogen (BUN) was 109f28 S.D. mg per 100 ml, mean serum creatinine (Cr) 13.2k3.8 S.D. mg per 100 ml, and mean serum bicarbonate *Partially supported by grants from the Division of Chronic Disease, CH 15-8, U.S. Public Health Service, Otho S.A. Sprague Foundation, and Kidney Research Fund of Passavant Pavilion. Certain observations were performed in the Clinical Research Center, Northwestern University Medical School, supported by Grant RR 48, Division of Research Resources, National Institutes of Health. TResearch Fellow. 1972-1974. 365
130180
180/100
16
18
14 12
17
M/28
M/30
M/30 M/45
M/30 M/60
M/39
M/45 M/48
M/61 41
5
6** 7***
10
I1
12
13
14 Mean
tposterior
DTR-deep
yes yes yes
yes
yes
yes
yes yes
yes
yes
yes
yes yes
yes
yes
yes
yes
yes
yes
pres. dec.
pres.
abs.
dec.
abs. dec.
dec.
dec. dec.
dec.
abs.
dec.
dec.
Periph. pulsest
dec.
dec.
dec.
abs.
abs.
dec.
dec. abs.
dec. dec.
dec.
dec. abs.
DTR
dialysis.
tendon reflexes (pateliar and ankle).
yes
yes
yes
yes
yes yes
yes
yes
yes
Edema Anasarca Peripheral
INCEPTIONOF MAINTENANCE DIALYSIS
18, 8, and 3 months, respectively, after onset of maintenance
congestion.
11
II
11t
II
IV I
yes
yes
II III
yes
yes yes
yes
IV IV
IV
III
IV
II
CC
AT
conduction velocity (peroneal nerve), normal range 43-57 m/set. abs.-absent, dec.-decreased.
transplant
tibia], dorsalis pedis.
tNCV-nerve pres.-present,
159189 34/14
16.5
5.2
loo/70
200190
168/108
140180 lOO,l70
180/110
144/90
190190
20
11
15 13
7
118/70
200194
blood pressure. CC--circulatory
*, **, ***-renal
BP-supine
S.D.
8 9
17 29
M/39
F/30
4
170180 200/l 10
22
20
M/51
F/32
1”
(grade)
(mm&$
(yr)
2 3
Diabetic retinop.
BP
Diabetes duration
Sex/ Age
Pat. no.
TABLE1. CLINICALDATA
44
no resp. 29.4
26
16
20 20.6
33
26
(m/set)
NCV
NPH 25
NPH 37
NPH 24
NPH 24
NPH 85 NPH 22
NPH 60
NPH 30
NPH 30
NPH 50
NPH 80
X
x
Therapy insulin oral agents (units/day)
Dialysis for Uremic Diabetic Nephropathy
367
(COa) 14.1 f 1.8 mEq S.D. per liter. Serum cholesterol ranged from 325 to 620 mg per 100 ml, and serum albumin from 1.4 to 4.5 g per 100 ml with levels of 2.5 g or less in eight patients. Proteinuria ranged from 1.Oto 33.7 g per 24 hr, exceeding 5 g in five cases. Hemodialysis by the twin-coil or parallel flow dialyzer was employed in 12 patients from twice to thrice weekly for a total of 18-30 hr. Access to the circulation was via external shunt in three and via A-V fistula in nine. Two patients (Nos. I and 13, Table 1) were treated by peritoneal dialysis twice weekly for a total of 48-52 hr per week, with standard dialysate solutions, by employing the repeated puncture technique or the Tenckhoff device [18]. Body weight, vital functions, hematocrit and blood glucose were monitored routinely with each dialysis. Blood urea nitrogen (BUN), serum creatinine (Cr), and electrolytes were determined at least once weekly before and after each dialysis, and serum proteins every 4-8 weeks. Nerve conduction velocity was measured initially, and serially during dialysis in nine cases. ‘rABLE
2.
hRlINEN-F
LABORAWRY
DAlA
AF INCk.PTION
OF MAINWNANCE
DIALYSIS
Serum
Fasting Pal. no.
Hct. (Y%J
serum glucose (mJzxJ
BUN
(wP/u)
Serum Cr (ms XJ
Serum co>
Strum albumin
(mEq/l.)
(g%)
Urine protein k/24 hr)
lesterol (mgo/,)
cho-
- _____. 14.0
15.0
1.4
2.8
520
Y5
4.6
16.0
2.5
17.0
440
210
132
17.7
14.0
3.5
2.5
185 I’)2
91
13.5
12.5
3.4
80
15.0
10.5
2.3
1.5 I.0
380 325
I*
29
140
2
28
240
3
25
4
18
5
17
85
580 620
6**
23
225
Ytl
16.0
13.2
1.6
7***
17
184
100
16.2
13.8
2.0
1.X 7.0
N
I’)
145
67
7.1
14.1
4.5
8.5
3Y5
465
Y
24
150
85
17.0
I I.0
2.3
33.7
415
10
20
135
147
9.1
14.0
1.‘)
I.2
405
II
24
160
135
15.5
17.0
3.Y
2.1
460
12
24
142
150
15.0
16.5
2.7
475
13
21
148
150
13.0
3.5
385
14
23
130
125
11.0
15.7 14.3
4.8 8.0
2.5
3.5
4’0
Mean
21.5
170
100
13.2
14.1
2.6
6.8
44’)
28
3.8
1.8
0.8
8.5
SD. *, **, ***-as
4.5
34.4
77.3
for Table 1. RESULTS
The data are summarized in Tables 3-5. Maintenance dialysis totalled 156.5 months for the whole group of patients, averaging 11.2 months per patient. In particular, six patients were on dialysis for 1.5-6 months, and the remainder for 8-30 months. Three patients (Nos. 1, 6, and 7) underwent renal transplantation 6, 8, and 18 months, respectively, after starting dialysis.
12
6 4
2
11
12 13
14
H-hemodialysis. P-peritoneal *, **, ***-as for Table 1.
3 21
9 10
F F
P, H H
none
none
n.c. n.c.
dec.
dec. none
dec.
n.c.
dec. n.c.
varied
n.c. n.c.
dialysis. F-arterio-venous
F
F
S F
s
F
F
F
F
F
s
Access
Insulin requirements
n.c. n.c.
n.c.
n.c.
n.c.
n.c.
n.c. n.c.
n.c.
n.c.
worse n.c.
n.c.
n.c.
Retinopathy
shunt. n.c.-no
36
6
8 6
12
conduction
2
2 5
4
4
6 2
2
8 12
4
7
10 17
54 1
velocity.
l/2
314 3
2 l/2 2
1
2 l/2
4 l/2
6 7
5 l/4
2 314
6 l/2 1 l/2
Hospital admissions Total Mos.
8
14
12
Work/ week hr
change. NCV-nerve
none partial
partial
partial
partial
40 no resp.
partial none
partial
partial
none
partial none
none
partial
Rehabilitation
12
no resp.
no resp.
12
23
21
(mpersec)
NCV
DIALYSIS IN 14 PATIENTS WITH DIABETIC NEPHROPATHY
fistula. S-external
COURSEOF MAINTENANCE
H
H
H H
H
H
15
8
6
H
12
6+* 7*++
H
H
18
8
H
30
3
4 5
2
1+
P H
Mos.
Dialysis
18 1 l/2
no.
Pat.
TABLE 3.
tttt
tttt
4
5
tttt
14
.<1
Xl
Xl
Xl
x2
xl
gangrene rt. foot
hepatitis
lung abscess
gangrene It. foot
‘t’ttt, before each dialysis; ttt,
x2
Xl
x4
Xl
FOR
x 4 shunt
WITH
yes
yes
Yes
yes
yes
yes
yes
Yes
yes
yes
yes
yes
Intractable heart failure, septicemia Acute hyperkalemia
Intractable heart failure
Septicemia
Rapidly progressive liver failure
Massive pulmonary hemorrhage, pseudomonas septicemia post transplant Multiple pulmonary embolism Acute myocardial infarction
Septicemia post transplant
Intractable heart failure, septicemia
Intractable heart failure
Acute myocardial infarction
yes
Cause of death
NEPHROPATHY
Bone marrow aplasia and septicemia post-transplant
Psychiatric care
DIABETIC
yes
Emotional problems
14 PATIENTS
Thrombosis
DIALYSIS
every 10 to 15 days; it, every 16 to 21 days; *, **, ***. as for Table 1.
x2
Xl
Pancreatitis
OF MAINTENANCE
other
IN COURSE
Infections systemic
COMPLICATIONS
peritoneal
CC., circulatory congestion;
tttt tttt
ttt
13
12
11
10
9
8
tttt
tt
3
6** 7***
tttt
C.C.
2
1*
Pat. no.
TABLE 4.
stated.
Patients
l-29
28-61
63.6:
80
48
78 28
24
n.s.
n.s.
62.5
100 n.s.
Mortality on dialysis t %!yr)
of the mortality rate.
10-35
27-55
14-30 n.s. mean 20.1
n.s. 23-73
25-49
n.s.
33-58 5-43
n.s.
10-73
n.s.
n.s.
n.s. 5-29
20-67
n.s. 22-72
age
Diabetes duration (yr)
deaths were not included in the computation
14
Present series
*The 3 post-transplant
n.s.-not
10
White et al. [ 171
9
n.s. 14
Chavamian et al. [ 141
SchupaketaL [15] Leonard et al. [ 161
12
29
12
Baskin er al. [lo]
Knepshiel et al. [ 121
20
Comty and Shapiro 191
Blagg et al. [ 1l]
2 44
total
Avram [ 71 Chazan et al. [8]
Reference
Remarks
Five patients died between A.5 and 6 months, 2 died at 1 yr, 3 between 15 and 21 months of starting dialysis. One patient alive at 30 months. Three patients died post-transplant
One patient had peritoneal dialysis only and died at 4 months. Nine patients had peritoneal and hemodialysis
Details not available
Details not available
Eight patients died within 4 to 28 months
Nine juvenile and 3 adult diabetics. Mortality significantly higher than in non-diabetics
Patients died between 1 and 6 months Only 8 patients survived longer than 3 months
TABLE5. MAINTENANCEDIALYSISFORDJABETICNEPHROPATHY WJTH UREMJA
_
Dialysis for Uremic Diabetic Nephropathy
371
Clinical course
Nitrogen retention and acidosis were readily controlled by dialysis: BUN decreased to an average of 37.3 mg per 100 ml, and serum creatinine (Cr) to 4.4 per 100 ml, while serum bicarbonate (COP) increased to an average of 20.2 mEq per liter. However, the clinical course was eventful in most patients because of varying complications. 1. Hospital admissions. (Table 3). The severity of complications present at the initial admission was such as to preclude discharge of one patient‘ (No. 2) who died within 1.5 months after inception of maintenance dialysis. The length of hospitalization for all admissions averaged 3.25 months per patient, ranging from 2 weeks to 7 months. Thus, the average hospital stay was about a third of the mean overall length of maintenance dialysis (11.2 months) per patient. 2. ItrwulitJrequirements. The dose of insulin needed to maintain fasting glucose between 90 and 110 mg per 100 ml decreased in four patients, and did not change in six. However, diabetes was di&ult to control in one patient (No. 4, Table 3), who required almost daily adjustment of insulin dose. 3. Cardiovascular complications. Features of circulatory congestion present in 11 patients at the initial admission were readily controlled by dialysis in two patients. However, congestive features frequently developed in the other nine patients. In several of these patients, development of hypotension during dialysis was common, precluding effective fluid removal, and six died of acute myocardial infarction or intractable heart failure (Table 4). 4. Infections. (Table 4). Septic complications and hepatitis caused or contributed to the demise of four patients during maintenance dialysis. One patient (No. 5) developed multiple intra-abdominal and pelvic abcesses after surgery for removal of bladder, spleen, and kidneys, which persisted until death I yr after the start of dialysis. The second patient (No. 10) developed hepatitis during the 21st month of dialysis, with liver failure which proved rapidly fatal. The third patient (No. 11) had recurrent septic thrombophlebitis secondary to infected gangrene of the right foot, which did not respond to aggressive chemotherapy, and he died of septicemia at I yr. The fourth patient (No. 13) who was on peritoneal dialysis, had two bouts of peritonitis with fatal septicemia during the fourth month of treatment. Additionally, the patient (No. 3) who is the longest survivor of the group, has manifested gangrene of the left foot, complicated by thrombophlebitis 30 months after the start of dialysis. 5. Thromboembolic complications. (Table 4). One patient (No. 8) experienced repeated clotting of the external shunt, which required several revisions. He eventually developed arterial thrombosis in the upper extremities and died of acute pulmonary embolism. 6. Pancreatitis. (Table 4). Two patients (Nos. 1 and 13) had recurrent pancreatitis, despite seemingly adequate control of uremia and diabetes. 7. Retinopathy. All patients had retinopathy of varying degree at the time of initial admission. Two were nearly blind, and a third (No. 3, Table 3) became nearly so after 30 months on dialysis.
372
C. HUANGet al.
8. Peripheral neuropathy. Peripheral neuropathy deteriorated or did not change in most cases. Significant decrease in nerve conduction velocity and muscle weakness of the lower extremities was noted in three patients. However, one patient (No. 10, Table 3) experienced marked improvement.
9. Rehabilitation. Three patients (Nos. 1, 3, and 10, Table 3) were able to resume limited work between dialyses and hospitalizations. Six were able to work only at home, helping their spouses with the household chores, and five were disabled to varying degrees. Emotional problems were common in nine patients, and psychiatric care for severe depression was required by five. 10. Survival. Survival rate according to life table analysis [19] was 54.8 per cent at 1 yr, and 16.4 per cent at 2 yr. The longest survivor has continued on dialysis for 30 months, but suffers from severe peripheral neuropathy and progressive visual impairment. Transplantation. Three patients (Nos. 1, 6, and 7, Tables l-4) underwent renal transplantation 6, 8, and 18 months, respectively, after maintenance dialysis. One patient received the allograft from a related living donor, and two received cadaveric allografts which, for one, included the pancreas as well. All patients died from 10 days to 3 months postoperatively with overwhelming infectious complications. DISCUSSION
Maintenance dialysis was of limited benefit to the patients included in this study. The clinical course was plagued in most patients by frequent bouts of edema, circulatory congestion, and various infectious complications. Repeated hospitalizations were required and meaningful rehabilitation was virtually impossible. The survival rate of 54.8 per cent at 1 yr, and of 16.4 per cent at 2 yr contrasts sharply with the rates of 83.7-92.9 per cent at 1 yr, and of 73-86.1 per cent at 2 yr, reported [l-5] for nondiabetic uremics on maintenance dialysis. Our own experience with such patients [6] shows survival rates of 95.6 per cent and 88.6 per cent at 1 and 2 yr, respectively. Several series of uremic diabetics on maintenance dialysis have been described. The data listed in Table 5 reveal that the yearly mortality rate ranged from 48 to 100 per cent in most series. However, Schupak et al. [15] and Knepshiel et al. [12] have experienced a mortality rate of 28 and 24 per cent, respectively. The discrepancy between their results and the data reported by others is not readily apparent and from the published information it is difficult to determine whether the clinical and laboratory features were less severe in Schupak’s and Knepshiel’s series. As to the patients included in this study, nearly all were in poor general condition at the inception of maintenance dialysis. All had edema with anasarca in seven, and 11 had congestive heart failure. All had retinopathy, which was severe in five, and all but one had evidence of peripheral neuropathy. The results of the present study as well as of others point out that maintenance dialysis does not alter the multisystem involvement of end-stage diabetic nephropathy, and potential for rehabilitation or extended survival is far inferior to that of patients without diabetes. This evidence underscores the need for clinical and laboratory criteria which might be helpful in anticipating the response of uremic diabetics to
Dialysis for Uremic Diabetic Nephropathy
373
maintenance dialysis. Chazan et al. [8] found that hyponatremia with anasarca was associated with the worst results. Watkins et al. [13] have proposed that the degree of hypoproteinemia and proteinuria provides a reliable prognostic indicator. The present observations do not permit conclusions in this regard since in nearly half the patients death was caused by intractable heart failure or acute myocardial infarction. Nonetheless, it cannot be excluded that protein depletion contributed to excessive fluid retention as well as to the general morbidity exhibited by most patients. The grim outlook for diabetics with uremia suggested by this and other studies does not necessarily imply hopelessness. Indeed, maintenance dialysis has a place in the management of these patients [16]. Application of more stringent criteria for patient selection, initiation of dialysis earlier, improved techniques, and, above all, attention to details will likely lead to better results [20]. SUMMARY Fourteen patients, aged 28-61 yr, with diabetic nephropathy and uremia were observed on maintenance dialysis for a total of 156.5 dialysis patient months (range: 1.5-30 months per patient). Clinical course on dialysis was eventful in most cases,
though nitrogen retention and acidosis were readily controlled. Bouts of circulatory congestion and severe fluid retention were frequent in nine patients, six of whom died of acute myocardial infarction or intractable heart failure. Septic complications and hepatitis caused or contributed to the demise of four patients, and thromboembolic complications to that of one patient. Rehabilitation on dialysis was limited in nine cases, and five remained disabled. Retinopathy was not improved. Emotional problems were common in nine patients, five of whom required psychiatric care. Ten patients died between 1.5 and 21 months after the start of dialysis, and only one survived over 30 months. Three patients underwent renal transplantation 6 to 18 months after inception of dialysis. They all died 10 days to 3 months after surgery of overwhelming septic complications. Survival rate on maintenance dialysis for the whole group was 54.8 per cent at 1 yr, and 16.4 per cent at 2 yr. REFERENCES Johnson WJ, O’Kane HO, Woods JE, Elveback LR: Survival of patients with end-stage renal disease. Mayo Clin Proc 48: 18-23, 1973 2. Lewis EJ, Foster DM, De la Fuente J, Scurlok C: Survival data for patients undergoing chronic intermittent hemodialysis. Ann Int Med 70: 311-315, 1969 3. Gross J, Kean WF, McDonald A: Survival and rehabilitation of patients on home hemodialysis. I.
Ann Int Med 78: 341-346, 1973
4. Neff M, Baez A, Slifkin R, Schupak E: Outpatient dialysis. Arch Int Med 131: 717-721, 1973 5. Lowrie EG, Lazarus LM, Mocelin AJ, Bailey GL, Hampers CL, Wilson RE, Merrill JP: 6. I. 8. 9. 10. C
Survival of patients undergoing chronic hemodialysis and renal transplantation. NEJM 288: 863-867, 1973 Roguska J, Simon NM, de1 Greco F, Krumlovsky FA: Ten-year experience with maintenance hemodialysis for chronic uremia. Trans Am Sot Artif Org 1974 (in press) Avram MM: in Proe Conference on Dialysis, Practical Work-Shop, New York, National Union Catalogue, April-June 1966, pp. 15-16 (abstract) Chazam BI, Rees SB, Balodimos MC, Younger D, Ferguson BD: Dialysis in diabetics. JAMA 209:2026-2030, 1969 Comty CM, Shapiro FL: Management and prognosis of diabetic patients treated by chronic hemodialysis. Am Soe Neph 5th Nat Mtg 5: 15, 1971 (abstract) Baskin S, Lawrence J, McNichol LJ: Chronic home dialysis of patients with diabetes mellitus. Am See Neph 5th Nat Mtg 5: 6, 1971 (abstract)
314 11. 12.
13. 14. 15. 16. 17. 18. 19. 20.
C. HUANG et al. Blagg CR, Esbach JW, Sawyer TK, Casaretto AA: Dialysis for end-stage diabetic nephropathy. Proc Clin Dial Transplant Forum 1: 133-135, 1971 Knepshiel J, Briggs %‘, Lazarus J, Cirksena’W, Bailey G, Seigel G, Hampers C, Schreiner G, Merrill JP: Diabetic nephropathy: Results of treatment with dialysis and transplantation. Int Cong Neph 5: 25, 1972 (abstract) Watkins P, Blainey J, Brewer D, Fitzgerald M, Malins J: The natural history of diabetic renal disease. Quart J Med 41: 437-454, 1972 Ghavamian M, Gutch CF, Kopp KF, Kolff WJ : The sad truth about hemodialysis in diabetic nephropathy. JAMA 222: 1386-1389, 1972 Schupak E, Neff MS, Slifkin R, Baez A: Diabetics in hemodialysis. JAMA 223: 1157, 1973 (letter) Leonard A, Comty M, Raij L, Rattazzi T, Wathen R, Shapiro F: The natural history of regular dialyzed diabetics. Trans Am Sot Artif Int Org 19: 282-286, 1973 White N, Snowden SA, Parsons V, Sheldon J, Bewick M: The management of terminal renal failure in diabetic patients with regular dialysis therapy. Nephron 11: 261-275, 1973 Tenckhoff H, Schechter HA: A bacteriologically safe peritoneal access device. Trans Am Sot ArtifInt Org 14: 181-186, 1968 Cutler S, Ederer F: Maximum utilization of the life table method in analyzing survival. J Chron Dis 8: 699-712, 1958 Jones KM, Ivanovich P: Peritoneal dialysis treatment for end-stage diabetic nephropathy. Proc Am Sot Extracorporeal Technology, 12th Tnternat Conf, Dallas, Texas, July 19, 1974 (in press)
MAINTENANCE DIALYSIS FOR DIABETIC NEPHROPATHY WITH UREMIA* C. HUANG,? F. DEL GRECO, P. IVANOVICH,F.
A. KRuMLovsKY, J. ROGUSKA,N. M. SIMONand J. HANO
Department of Medicine, Northwestern University Medical School, Northwestern Memorial Hospital, and V.A. Research Hospital, Chicago, Illinois 60611, U.S.A. (Received 7 August 1974)
NOTABLEsuccesses have been achieved with maintenance dialysis for nondiabetic uremic patients, and survival rates of 83.7 and 95.6 per cent at 1 yr have been reported [l-6]. By contrast, the value of long-term dialysis for treating patients with diabetic nephropathy and uremia is still in doubt. The pertinent available evidence is conflicting, and rates of rehabilitation, morbidity and mortality vary greatly [7-171. Since the availability of maintenance dialysis is being greatly expanded, an increasing number of diabetics with uremia is likely to be placed on such therapy. It is, therefore, of considerable practical importance to evaluate the experience available to date. Between January, 1963 and December, 1973, 150 patients with chronic uremia have been placed on maintenance dialysis at our center. The purpose of this report is to describe 14 of these patients who had uremia caused by diabetic nephropathy. MATERIALS
AND
METHODS
The clinical findings on admission are summarized in Table 1. There were 12 men and 2 women, ranging in age from 28 to 61 yr. The patients had known diabetes mellitus for 7-29 yr. Six patients had had diabetes since childhood, while in eight the disease was of adult onset. Hypertension was present in nine patients, and features of circulatory congestion with heart failure were noted in 11. All patients had edema, with anasarca in seven. Two patients were partially blind, and the remainder had varying degrees of retinopathy. Peripheral neuropathy, as evidenced by decreased deep tendon reflexes and nerve conduction velocity studies, was present in 13 cases, and diminished or absent peripheral pulses were found in 12. The initial laboratory data are listed in Table 2. All patients had anemia of varying degree. Mean blood urea nitrogen (BUN) was 109f28 S.D. mg per 100 ml, mean serum creatinine (Cr) 13.2k3.8 S.D. mg per 100 ml, and mean serum bicarbonate *Partially supported by grants from the Division of Chronic Disease, CH 15-8, U.S. Public Health Service, Otho S.A. Sprague Foundation, and Kidney Research Fund of Passavant Pavilion. Certain observations were performed in the Clinical Research Center, Northwestern University Medical School, supported by Grant RR 48, Division of Research Resources, National Institutes of Health. TResearch Fellow. 1972-1974. 365
130180
180/100
16
18
14 12
17
M/28
M/30
M/30 M/45
M/30 M/60
M/39
M/45 M/48
M/61 41
5
6** 7***
10
I1
12
13
14 Mean
tposterior
DTR-deep
yes yes yes
yes
yes
yes
yes yes
yes
yes
yes
yes yes
yes
yes
yes
yes
yes
yes
pres. dec.
pres.
abs.
dec.
abs. dec.
dec.
dec. dec.
dec.
abs.
dec.
dec.
Periph. pulsest
dec.
dec.
dec.
abs.
abs.
dec.
dec. abs.
dec. dec.
dec.
dec. abs.
DTR
dialysis.
tendon reflexes (pateliar and ankle).
yes
yes
yes
yes
yes yes
yes
yes
yes
Edema Anasarca Peripheral
INCEPTIONOF MAINTENANCE DIALYSIS
18, 8, and 3 months, respectively, after onset of maintenance
congestion.
11
II
11t
II
IV I
yes
yes
II III
yes
yes yes
yes
IV IV
IV
III
IV
II
CC
AT
conduction velocity (peroneal nerve), normal range 43-57 m/set. abs.-absent, dec.-decreased.
transplant
tibia], dorsalis pedis.
tNCV-nerve pres.-present,
159189 34/14
16.5
5.2
loo/70
200190
168/108
140180 lOO,l70
180/110
144/90
190190
20
11
15 13
7
118/70
200194
blood pressure. CC--circulatory
*, **, ***-renal
BP-supine
S.D.
8 9
17 29
M/39
F/30
4
170180 200/l 10
22
20
M/51
F/32
1”
(grade)
(mm&$
(yr)
2 3
Diabetic retinop.
BP
Diabetes duration
Sex/ Age
Pat. no.
TABLE1. CLINICALDATA
44
no resp. 29.4
26
16
20 20.6
33
26
(m/set)
NCV
NPH 25
NPH 37
NPH 24
NPH 24
NPH 85 NPH 22
NPH 60
NPH 30
NPH 30
NPH 50
NPH 80
X
x
Therapy insulin oral agents (units/day)
Dialysis for Uremic Diabetic Nephropathy
367
(COa) 14.1 f 1.8 mEq S.D. per liter. Serum cholesterol ranged from 325 to 620 mg per 100 ml, and serum albumin from 1.4 to 4.5 g per 100 ml with levels of 2.5 g or less in eight patients. Proteinuria ranged from 1.Oto 33.7 g per 24 hr, exceeding 5 g in five cases. Hemodialysis by the twin-coil or parallel flow dialyzer was employed in 12 patients from twice to thrice weekly for a total of 18-30 hr. Access to the circulation was via external shunt in three and via A-V fistula in nine. Two patients (Nos. I and 13, Table 1) were treated by peritoneal dialysis twice weekly for a total of 48-52 hr per week, with standard dialysate solutions, by employing the repeated puncture technique or the Tenckhoff device [18]. Body weight, vital functions, hematocrit and blood glucose were monitored routinely with each dialysis. Blood urea nitrogen (BUN), serum creatinine (Cr), and electrolytes were determined at least once weekly before and after each dialysis, and serum proteins every 4-8 weeks. Nerve conduction velocity was measured initially, and serially during dialysis in nine cases. ‘rABLE
2.
hRlINEN-F
LABORAWRY
DAlA
AF INCk.PTION
OF MAINWNANCE
DIALYSIS
Serum
Fasting Pal. no.
Hct. (Y%J
serum glucose (mJzxJ
BUN
(wP/u)
Serum Cr (ms XJ
Serum co>
Strum albumin
(mEq/l.)
(g%)
Urine protein k/24 hr)
lesterol (mgo/,)
cho-
- _____. 14.0
15.0
1.4
2.8
520
Y5
4.6
16.0
2.5
17.0
440
210
132
17.7
14.0
3.5
2.5
185 I’)2
91
13.5
12.5
3.4
80
15.0
10.5
2.3
1.5 I.0
380 325
I*
29
140
2
28
240
3
25
4
18
5
17
85
580 620
6**
23
225
Ytl
16.0
13.2
1.6
7***
17
184
100
16.2
13.8
2.0
1.X 7.0
N
I’)
145
67
7.1
14.1
4.5
8.5
3Y5
465
Y
24
150
85
17.0
I I.0
2.3
33.7
415
10
20
135
147
9.1
14.0
1.‘)
I.2
405
II
24
160
135
15.5
17.0
3.Y
2.1
460
12
24
142
150
15.0
16.5
2.7
475
13
21
148
150
13.0
3.5
385
14
23
130
125
11.0
15.7 14.3
4.8 8.0
2.5
3.5
4’0
Mean
21.5
170
100
13.2
14.1
2.6
6.8
44’)
28
3.8
1.8
0.8
8.5
SD. *, **, ***-as
4.5
34.4
77.3
for Table 1. RESULTS
The data are summarized in Tables 3-5. Maintenance dialysis totalled 156.5 months for the whole group of patients, averaging 11.2 months per patient. In particular, six patients were on dialysis for 1.5-6 months, and the remainder for 8-30 months. Three patients (Nos. 1, 6, and 7) underwent renal transplantation 6, 8, and 18 months, respectively, after starting dialysis.
12
6 4
2
11
12 13
14
H-hemodialysis. P-peritoneal *, **, ***-as for Table 1.
3 21
9 10
F F
P, H H
none
none
n.c. n.c.
dec.
dec. none
dec.
n.c.
dec. n.c.
varied
n.c. n.c.
dialysis. F-arterio-venous
F
F
S F
s
F
F
F
F
F
s
Access
Insulin requirements
n.c. n.c.
n.c.
n.c.
n.c.
n.c.
n.c. n.c.
n.c.
n.c.
worse n.c.
n.c.
n.c.
Retinopathy
shunt. n.c.-no
36
6
8 6
12
conduction
2
2 5
4
4
6 2
2
8 12
4
7
10 17
54 1
velocity.
l/2
314 3
2 l/2 2
1
2 l/2
4 l/2
6 7
5 l/4
2 314
6 l/2 1 l/2
Hospital admissions Total Mos.
8
14
12
Work/ week hr
change. NCV-nerve
none partial
partial
partial
partial
40 no resp.
partial none
partial
partial
none
partial none
none
partial
Rehabilitation
12
no resp.
no resp.
12
23
21
(mpersec)
NCV
DIALYSIS IN 14 PATIENTS WITH DIABETIC NEPHROPATHY
fistula. S-external
COURSEOF MAINTENANCE
H
H
H H
H
H
15
8
6
H
12
6+* 7*++
H
H
18
8
H
30
3
4 5
2
1+
P H
Mos.
Dialysis
18 1 l/2
no.
Pat.
TABLE 3.
tttt
tttt
4
5
tttt
14
.<1
Xl
Xl
Xl
x2
xl
gangrene rt. foot
hepatitis
lung abscess
gangrene It. foot
‘t’ttt, before each dialysis; ttt,
x2
Xl
x4
Xl
FOR
x 4 shunt
WITH
yes
yes
Yes
yes
yes
yes
yes
Yes
yes
yes
yes
yes
Intractable heart failure, septicemia Acute hyperkalemia
Intractable heart failure
Septicemia
Rapidly progressive liver failure
Massive pulmonary hemorrhage, pseudomonas septicemia post transplant Multiple pulmonary embolism Acute myocardial infarction
Septicemia post transplant
Intractable heart failure, septicemia
Intractable heart failure
Acute myocardial infarction
yes
Cause of death
NEPHROPATHY
Bone marrow aplasia and septicemia post-transplant
Psychiatric care
DIABETIC
yes
Emotional problems
14 PATIENTS
Thrombosis
DIALYSIS
every 10 to 15 days; it, every 16 to 21 days; *, **, ***. as for Table 1.
x2
Xl
Pancreatitis
OF MAINTENANCE
other
IN COURSE
Infections systemic
COMPLICATIONS
peritoneal
CC., circulatory congestion;
tttt tttt
ttt
13
12
11
10
9
8
tttt
tt
3
6** 7***
tttt
C.C.
2
1*
Pat. no.
TABLE 4.
stated.
Patients
l-29
28-61
63.6:
80
48
78 28
24
n.s.
n.s.
62.5
100 n.s.
Mortality on dialysis t %!yr)
of the mortality rate.
10-35
27-55
14-30 n.s. mean 20.1
n.s. 23-73
25-49
n.s.
33-58 5-43
n.s.
10-73
n.s.
n.s.
n.s. 5-29
20-67
n.s. 22-72
age
Diabetes duration (yr)
deaths were not included in the computation
14
Present series
*The 3 post-transplant
n.s.-not
10
White et al. [ 171
9
n.s. 14
Chavamian et al. [ 141
SchupaketaL [15] Leonard et al. [ 161
12
29
12
Baskin er al. [lo]
Knepshiel et al. [ 121
20
Comty and Shapiro 191
Blagg et al. [ 1l]
2 44
total
Avram [ 71 Chazan et al. [8]
Reference
Remarks
Five patients died between A.5 and 6 months, 2 died at 1 yr, 3 between 15 and 21 months of starting dialysis. One patient alive at 30 months. Three patients died post-transplant
One patient had peritoneal dialysis only and died at 4 months. Nine patients had peritoneal and hemodialysis
Details not available
Details not available
Eight patients died within 4 to 28 months
Nine juvenile and 3 adult diabetics. Mortality significantly higher than in non-diabetics
Patients died between 1 and 6 months Only 8 patients survived longer than 3 months
TABLE5. MAINTENANCEDIALYSISFORDJABETICNEPHROPATHY WJTH UREMJA
_
Dialysis for Uremic Diabetic Nephropathy
371
Clinical course
Nitrogen retention and acidosis were readily controlled by dialysis: BUN decreased to an average of 37.3 mg per 100 ml, and serum creatinine (Cr) to 4.4 per 100 ml, while serum bicarbonate (COP) increased to an average of 20.2 mEq per liter. However, the clinical course was eventful in most patients because of varying complications. 1. Hospital admissions. (Table 3). The severity of complications present at the initial admission was such as to preclude discharge of one patient‘ (No. 2) who died within 1.5 months after inception of maintenance dialysis. The length of hospitalization for all admissions averaged 3.25 months per patient, ranging from 2 weeks to 7 months. Thus, the average hospital stay was about a third of the mean overall length of maintenance dialysis (11.2 months) per patient. 2. ItrwulitJrequirements. The dose of insulin needed to maintain fasting glucose between 90 and 110 mg per 100 ml decreased in four patients, and did not change in six. However, diabetes was di&ult to control in one patient (No. 4, Table 3), who required almost daily adjustment of insulin dose. 3. Cardiovascular complications. Features of circulatory congestion present in 11 patients at the initial admission were readily controlled by dialysis in two patients. However, congestive features frequently developed in the other nine patients. In several of these patients, development of hypotension during dialysis was common, precluding effective fluid removal, and six died of acute myocardial infarction or intractable heart failure (Table 4). 4. Infections. (Table 4). Septic complications and hepatitis caused or contributed to the demise of four patients during maintenance dialysis. One patient (No. 5) developed multiple intra-abdominal and pelvic abcesses after surgery for removal of bladder, spleen, and kidneys, which persisted until death I yr after the start of dialysis. The second patient (No. 10) developed hepatitis during the 21st month of dialysis, with liver failure which proved rapidly fatal. The third patient (No. 11) had recurrent septic thrombophlebitis secondary to infected gangrene of the right foot, which did not respond to aggressive chemotherapy, and he died of septicemia at I yr. The fourth patient (No. 13) who was on peritoneal dialysis, had two bouts of peritonitis with fatal septicemia during the fourth month of treatment. Additionally, the patient (No. 3) who is the longest survivor of the group, has manifested gangrene of the left foot, complicated by thrombophlebitis 30 months after the start of dialysis. 5. Thromboembolic complications. (Table 4). One patient (No. 8) experienced repeated clotting of the external shunt, which required several revisions. He eventually developed arterial thrombosis in the upper extremities and died of acute pulmonary embolism. 6. Pancreatitis. (Table 4). Two patients (Nos. 1 and 13) had recurrent pancreatitis, despite seemingly adequate control of uremia and diabetes. 7. Retinopathy. All patients had retinopathy of varying degree at the time of initial admission. Two were nearly blind, and a third (No. 3, Table 3) became nearly so after 30 months on dialysis.
372
C. HUANGet al.
8. Peripheral neuropathy. Peripheral neuropathy deteriorated or did not change in most cases. Significant decrease in nerve conduction velocity and muscle weakness of the lower extremities was noted in three patients. However, one patient (No. 10, Table 3) experienced marked improvement.
9. Rehabilitation. Three patients (Nos. 1, 3, and 10, Table 3) were able to resume limited work between dialyses and hospitalizations. Six were able to work only at home, helping their spouses with the household chores, and five were disabled to varying degrees. Emotional problems were common in nine patients, and psychiatric care for severe depression was required by five. 10. Survival. Survival rate according to life table analysis [19] was 54.8 per cent at 1 yr, and 16.4 per cent at 2 yr. The longest survivor has continued on dialysis for 30 months, but suffers from severe peripheral neuropathy and progressive visual impairment. Transplantation. Three patients (Nos. 1, 6, and 7, Tables l-4) underwent renal transplantation 6, 8, and 18 months, respectively, after maintenance dialysis. One patient received the allograft from a related living donor, and two received cadaveric allografts which, for one, included the pancreas as well. All patients died from 10 days to 3 months postoperatively with overwhelming infectious complications. DISCUSSION
Maintenance dialysis was of limited benefit to the patients included in this study. The clinical course was plagued in most patients by frequent bouts of edema, circulatory congestion, and various infectious complications. Repeated hospitalizations were required and meaningful rehabilitation was virtually impossible. The survival rate of 54.8 per cent at 1 yr, and of 16.4 per cent at 2 yr contrasts sharply with the rates of 83.7-92.9 per cent at 1 yr, and of 73-86.1 per cent at 2 yr, reported [l-5] for nondiabetic uremics on maintenance dialysis. Our own experience with such patients [6] shows survival rates of 95.6 per cent and 88.6 per cent at 1 and 2 yr, respectively. Several series of uremic diabetics on maintenance dialysis have been described. The data listed in Table 5 reveal that the yearly mortality rate ranged from 48 to 100 per cent in most series. However, Schupak et al. [15] and Knepshiel et al. [12] have experienced a mortality rate of 28 and 24 per cent, respectively. The discrepancy between their results and the data reported by others is not readily apparent and from the published information it is difficult to determine whether the clinical and laboratory features were less severe in Schupak’s and Knepshiel’s series. As to the patients included in this study, nearly all were in poor general condition at the inception of maintenance dialysis. All had edema with anasarca in seven, and 11 had congestive heart failure. All had retinopathy, which was severe in five, and all but one had evidence of peripheral neuropathy. The results of the present study as well as of others point out that maintenance dialysis does not alter the multisystem involvement of end-stage diabetic nephropathy, and potential for rehabilitation or extended survival is far inferior to that of patients without diabetes. This evidence underscores the need for clinical and laboratory criteria which might be helpful in anticipating the response of uremic diabetics to
Dialysis for Uremic Diabetic Nephropathy
373
maintenance dialysis. Chazan et al. [8] found that hyponatremia with anasarca was associated with the worst results. Watkins et al. [13] have proposed that the degree of hypoproteinemia and proteinuria provides a reliable prognostic indicator. The present observations do not permit conclusions in this regard since in nearly half the patients death was caused by intractable heart failure or acute myocardial infarction. Nonetheless, it cannot be excluded that protein depletion contributed to excessive fluid retention as well as to the general morbidity exhibited by most patients. The grim outlook for diabetics with uremia suggested by this and other studies does not necessarily imply hopelessness. Indeed, maintenance dialysis has a place in the management of these patients [16]. Application of more stringent criteria for patient selection, initiation of dialysis earlier, improved techniques, and, above all, attention to details will likely lead to better results [20]. SUMMARY Fourteen patients, aged 28-61 yr, with diabetic nephropathy and uremia were observed on maintenance dialysis for a total of 156.5 dialysis patient months (range: 1.5-30 months per patient). Clinical course on dialysis was eventful in most cases,
though nitrogen retention and acidosis were readily controlled. Bouts of circulatory congestion and severe fluid retention were frequent in nine patients, six of whom died of acute myocardial infarction or intractable heart failure. Septic complications and hepatitis caused or contributed to the demise of four patients, and thromboembolic complications to that of one patient. Rehabilitation on dialysis was limited in nine cases, and five remained disabled. Retinopathy was not improved. Emotional problems were common in nine patients, five of whom required psychiatric care. Ten patients died between 1.5 and 21 months after the start of dialysis, and only one survived over 30 months. Three patients underwent renal transplantation 6 to 18 months after inception of dialysis. They all died 10 days to 3 months after surgery of overwhelming septic complications. Survival rate on maintenance dialysis for the whole group was 54.8 per cent at 1 yr, and 16.4 per cent at 2 yr. REFERENCES Johnson WJ, O’Kane HO, Woods JE, Elveback LR: Survival of patients with end-stage renal disease. Mayo Clin Proc 48: 18-23, 1973 2. Lewis EJ, Foster DM, De la Fuente J, Scurlok C: Survival data for patients undergoing chronic intermittent hemodialysis. Ann Int Med 70: 311-315, 1969 3. Gross J, Kean WF, McDonald A: Survival and rehabilitation of patients on home hemodialysis. I.
Ann Int Med 78: 341-346, 1973
4. Neff M, Baez A, Slifkin R, Schupak E: Outpatient dialysis. Arch Int Med 131: 717-721, 1973 5. Lowrie EG, Lazarus LM, Mocelin AJ, Bailey GL, Hampers CL, Wilson RE, Merrill JP: 6. I. 8. 9. 10. C
Survival of patients undergoing chronic hemodialysis and renal transplantation. NEJM 288: 863-867, 1973 Roguska J, Simon NM, de1 Greco F, Krumlovsky FA: Ten-year experience with maintenance hemodialysis for chronic uremia. Trans Am Sot Artif Org 1974 (in press) Avram MM: in Proe Conference on Dialysis, Practical Work-Shop, New York, National Union Catalogue, April-June 1966, pp. 15-16 (abstract) Chazam BI, Rees SB, Balodimos MC, Younger D, Ferguson BD: Dialysis in diabetics. JAMA 209:2026-2030, 1969 Comty CM, Shapiro FL: Management and prognosis of diabetic patients treated by chronic hemodialysis. Am Soe Neph 5th Nat Mtg 5: 15, 1971 (abstract) Baskin S, Lawrence J, McNichol LJ: Chronic home dialysis of patients with diabetes mellitus. Am See Neph 5th Nat Mtg 5: 6, 1971 (abstract)
314 11. 12.
13. 14. 15. 16. 17. 18. 19. 20.
C. HUANG et al. Blagg CR, Esbach JW, Sawyer TK, Casaretto AA: Dialysis for end-stage diabetic nephropathy. Proc Clin Dial Transplant Forum 1: 133-135, 1971 Knepshiel J, Briggs %‘, Lazarus J, Cirksena’W, Bailey G, Seigel G, Hampers C, Schreiner G, Merrill JP: Diabetic nephropathy: Results of treatment with dialysis and transplantation. Int Cong Neph 5: 25, 1972 (abstract) Watkins P, Blainey J, Brewer D, Fitzgerald M, Malins J: The natural history of diabetic renal disease. Quart J Med 41: 437-454, 1972 Ghavamian M, Gutch CF, Kopp KF, Kolff WJ : The sad truth about hemodialysis in diabetic nephropathy. JAMA 222: 1386-1389, 1972 Schupak E, Neff MS, Slifkin R, Baez A: Diabetics in hemodialysis. JAMA 223: 1157, 1973 (letter) Leonard A, Comty M, Raij L, Rattazzi T, Wathen R, Shapiro F: The natural history of regular dialyzed diabetics. Trans Am Sot Artif Int Org 19: 282-286, 1973 White N, Snowden SA, Parsons V, Sheldon J, Bewick M: The management of terminal renal failure in diabetic patients with regular dialysis therapy. Nephron 11: 261-275, 1973 Tenckhoff H, Schechter HA: A bacteriologically safe peritoneal access device. Trans Am Sot ArtifInt Org 14: 181-186, 1968 Cutler S, Ederer F: Maximum utilization of the life table method in analyzing survival. J Chron Dis 8: 699-712, 1958 Jones KM, Ivanovich P: Peritoneal dialysis treatment for end-stage diabetic nephropathy. Proc Am Sot Extracorporeal Technology, 12th Tnternat Conf, Dallas, Texas, July 19, 1974 (in press)