Henry Ford Hospital Medical Journal Henry Ford Hospital Medical Journal

Manuscript 2013

Treatment of Uremic Diabetic Patients: Hemodialysis or Treatment of Uremic Diabetic Patients: Hemodialysis or

Transplantation? Transplantation?

Godofredo Santiago

Cosme Cruz

Francis Dumler

Pedro Cortes

Stanley Dienst

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Treatment of Uremic Diabetic Patients: Hemodialysis or Transplantation? Treatment of Uremic Diabetic Patients: Hemodialysis or Transplantation?

Authors Authors Godofredo Santiago, Cosme Cruz, Francis Dumler, Pedro Cortes, Stanley Dienst, Sandra Parnell, Maxine Uniewski, and Nathan W. Levin

Henry Ford Hosp Med Journal

Vol 26, No 3, 1978

Treatment of Uremic Diabetic Patients: Hemodialysis or Transplantation?

Godofredo Santiago, MD,* Cosme Cruz, MD,* Francis Dumler, MD,* Pedro Cortes, MD,* Stanley Dienst, MD,** Sandra Parnell, RN, BS, Maxine Uniewski, RN, and Nathan W. Levin, MD*

Eighty-one patients with chronic renal failure associated with or secondary to diabetic nephropathy were treated with dialysis and/or transplant. Twenty-five had juvenile di­abetes and 56 had adult onset diabetes. Juvenile diabetics did poorly on hemodialysis with 13 patients having a 19% four-year survival rate, whereas those who had cadaveric transplantation did well with a four-year patient and graft survival rate of 56% in nine patients. The three juvenile diabetics who received related kidney grafts are presently alive with good function. Patients with adult onset diabetes did well on hemodialysis with a four-year survival rate of 63% in 45 patients. In this last group 11 patients received cadaveric transplants, but none survived 18 months.

A major cause of death in diabetes mellitus is diabetic nephropathy with progression to terminal renal failure. Death from uremia occurs at a mean of 2.7 years from the time renal insufficiency is initially detected unlessdialysisor transplantation are performed.

There has been reluctance to accept uremic diabetics to chronic hemodialysis programs because multiple diabetic complications including retinopathy, neuropathy, autono­mic disorder, and arterial disease are already present. As dialysis became more widely available, it became clear that chronic dialysis treatment of diabetics is unsatisfactory compared to nondiabetic patients in regard to mortality and morbidity.^'" Rapid progression of retinopathy and neuropa­thy has been observed. It has also been reported that 70% of all diabetics are dead three years after dialysis' has been initiated.

Najarian and others have recently demonstrated the success of renal transplantation in juvenile onset diabetes.'' Eighty-eight of 132 patients (67%) were alive, and 81 of 132 grafts were function ing from one to five years after transplantation. Ninety-six kidneys were obtained from living related do­nors, and 36 were from cadaver donors. They strongly advocated thattransplantation be the treatmentof choice for juvenile diabetics in spite of the higher risk involved.

In order to determine the advantages and disadvantages of hemodialysis and transplantation as treatment for end-stage kidney disease in diabetes, we have analyzed our experi­ence in 81 diabetic patients over a four-year period.

Submitted for publication: August 14, 1978 Accepted for publication: September 15, 1978

* Department of Medicine, Division of Nephrology, Henry Ford Hospital

** Department of Surgery, Section of Transplantation, Henry Ford Hospital

Address reprint requests to Dr. Santiago, Division of Nephrology, Henry Ford Hospital, 2799 W Grand Blvd, Detroit, Ml 48202

Materials and Methods In four years, we have treated 81 patients with insulin and/ororal-agent dependent diabetes. Age and sex charac­teristics are summarized in Table I. Twenty-five were juve­nile onset diabetics, and 56 were adult onset diabetics. Patients who had the diagnosis of diabetes mellitus before age 18 were considered juvenile onset diabetics, while those diagnosed after 18 were considered adult onset diabetics. Although some error may have been introduced due to the

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Santiago, Cruz, Dumler, ef al

TABLE I

AGE AND SEX OF DIABETIC POPULATION

JUVENILE DIABETIC ADULT DIABETIC

DIA

LY

SIS

Male Female Male Female

DIA

LY

SIS

< AGE 1 AGE # AGE # AGi:

DIA

LY

SIS

II 37.5 1 33.0 21 57.0 24 59.9

TR

AN

S P

UN

T

5 38.4 8 35.0 9 52.9 2 43.0

1.0

0.8 H

0.6

0.4

0.2

HOME DIALYSIS (17)

ADULT DIABETIC (58)

NON DIABETIC (347)

JUVENILE DIABETIC (23)

o • • — ^ o

~l 1 1 1 1 1 1 1 1 3 6 12 18 24 30 36 42 48

MONTHS

Fig.1

Patient Survival on Dialysis

Patients who had graft failure remain in the transplant group.

presence of young patients with maturity onset diabetes, the clinical picture of our patients diagnosed with juvenile diabetes has not been compatible with this possibility.

Twenty-four patients received a transplant, and 56 were treated with chronic intermittent hemodialysis. Patients were transplanted according to the procedure described by Simmons, eta/.'Those on hemodialysis were dial yzed three times a week for an average of four hours per treatment, using hollow fiber kidneys with 2.5 square meter surface area and with single-pass dialysis machines.

Cumulative patient and kidney survival statistics were cal­culated by the life table method.° Causes of death were compiled and tabulated in each group.

Results Fifty-one of the 81 diabetic patients (63%) are alive with a mean treatment period of 19.8 months. Figure 1 compares thecumulative patient survival of adult and juvenile diabet­ics to the nondiabetic dialysis population. Both adult diabet­ics and nondiabetics have a similar four-year survival rate. However, juvenile diabetics did not benefit from dialysis.

In Figure 2, our diabetic patients are divided according to juvenile or adult onset group and according to donor source. Our experience in related diabetic transplants is limited to three patients, who are all alive at this time. Juvenile, cadaveric transplant patients did well with 57% alive atfouryears, in contrast to adult onset diabetics, none of whom survived over 18 months after transplantation.

Figure 3 shows the data on kidney graft survival. To date, the three juvenile diabetics have good functioning grafts at 56, 36, and 30 months, respectively. The juvenile diabetic.

JUVENILE DIABETIC RELATED (3)

3 m? •? r ^ 17 y

NON-DIABETIC RELATED (19)

NON-DIABETIC CADAVER (97)

• • •o oo

JUVENILE DIABETIC CADAVER (10)

ADULT DIABETIC CADAVER (11)

/ t i l l ! -I <f

12 18 24 30 36 42 48

MONTHS

Fig. 2

Transplant Patient Survival

JUVENILE DIABETIC RELATED (3)

NON-DIABETIC RELATED (19)

JUVENILE DIABETIC CADAVER (10)

NON-DIABETIC CADAVER (97) o o

ADULT DIABETIC CADAVER (11)

Fig. 3

Kidney Graft Survival

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Treatment of Uremic Diabetic Patients

cadaver kidney did comparatively well with a 56% four-year survival rate.

The causes of death are listed in Table II. The source of this information was the autopsy reports of 13 patients and the death certificates of the 14 patients who did not have postmortem exam inations. Compi ications of d iabetes as the primary or secondary cause of death were considered when death was associated with severe hypo- or hyperglycemia and/or severe autonomic neuropathy. Complications of d iabetes accounted for the greatest number of deaths among juvenile diabetics on dialysis, while cardiovascular deaths predominate in the adult onset patients who had received transplants. Infection as a cause of death was highest in the juvenile diabetic transplants (100%), with septicemia being the most common infection. Other infections consisted of meningitis, staphylococcal empyema, and hyperinfection with Strongyloides. Ofthe infectious causes of death in adult diabetic transplants (50%), 30% were dueto septicemia and 20% to pneumonia. Only 16% of those adult onset diabetics on hemodialysis died with infection, while none of the juvenile diabetics on hemodialysis did so.

Discussion Diabetic nephropathy causing renal failure is the second most common diagnosis in the end-stage renal disease program at Henry Ford Hospital. It was found in 81 of 354 patients (23%) who presented with chronic renal failure during the study period. This increase in diabetic patients maybe due in part to the active diabetes clinic at our center as well as to the recent trend towards more liberal dialysis acceptance pol icies here and elsewhere. In our total of 354 patients, hypertensive nephrosclerosis was the lead ing diag­nosis (31%). This differs from reports at other centers where chronic glomerulonephritis is the most commonly reported cause of renal failure.

Regardless of diabetic complications, patients with terminal renal failure were unselected. Except for those with active infection, recent myocardial infarction, age over 60 years, and extreme debility, transplantation was encouraged. The final decision remained with the patient, who, after the possible outcomes were explained, could elect to stay on hemodialysis or be transplanted. Those who chose to stay on hemodialysis did so because of fear of major surgery, social reasons, and, in a few cases, religious belief.

Our experience with juvenile onset diabetic patients sup­ports the conclusions of previous series.' Our results show that this group of patients did poody on chronic hemo­dialysis, with 19% cumulative life table survival at four years. However, with cadaveric transplantation, the patient survival and graft survival at four years is 56%, which does

TABLE II CAUSES OF DEATH (PRIMARY OR SECONDARY)

DIABETIC HEMODIALYSIS ONLY DIABETIC TRANSPUNT

Complications of Diabetes

75%

MT;

It''.

infection

Cardiac

Complications of Diabetes

71";-

5751

ADULT

Cardiac

i nfection

Complications of Diabetes

Complications ol Diabetes Jl%

Cardiac

16% Infection

71%

0%

ADULT

Cardiac

Infection

Complications of Diabetes

JUVENILE

757. Infection I0O7.

5I». Cardiac 23%

Complications of Diabetes l.r.

not differ significantly from the rate for the nondiabetic cadaver transplant group.

The superiority of transplantation over hemodialysis as a method of managing end-stage kidney disease due to juve­nile onset diabetes is impressive enough to make it the treatment of choice in such patients. This should not hide the fact that there is a higher incidence of complications associated with marked increased morbidity in juvenile diabetics than in nondiabetic transplantation patients. It has also been reported that diabetic lesions may reoccur in the transplanted kidney, although this factor has not yet caused functional deterioration in the transplanted graft.^"

Juvenile diabetics have rapid progression of their diabetic complications which contributed directly in most cases to their early death on hemodialysis therapy Stabilization of these complications has been reported in previous trans­plants, which may in part explain their increased survival after successful kidney transplantation. Infection remains the most common cause of death after transplantation.

In marked contrast, adult onset diabetics, in spite of already advanced age with onset of uremia, did reasonably well on chronic hemodialysis therapy The patient survival at four years of 63% does not significantly differ from the rate for the nondiabetic dialysis population. As a group, adult onset diabetics did very poorly with transplantation with all of our patients dead at 18 months.

This find ing would suggest that adult onset diabetic patients with end-stage kidney disease should be treated with hemo-dialysis or peritoneal dialysis therapy rather than by renal transplantation. Most of the mortality in this group was caused by death from coronary vascular disease, which suggests that advanced artherosclerosis is usually present by the time their kidneys fail.

In some centers," chronic peritoneal dialysis is used pre­dominantly fortreating chronic renal failure due to diabetes. Its major advantage is that it can be carried out without the

29

Santiago, Cruz, Dumler, ef al

use of heparin, which has been claimed to aggravate retinal hemorrhage leading to deterioration of vision. Our experi­ence with this form of therapy is limited to four patients, for whom it has been a satisfactory substitute when hemo­dialysis was not feasible. We have used it in cases of lossof all possible access sites, severe cardiovascular instability, and severe autonomic dysfunction causing orthostatic hy­potension. Advances in peritoneal dialysis technology may reduce the associated complications such as infections, make it less time consuming, and thus make it a more attractive alternative than in its present form.

In this series, except for a few recent cases, dialysis and/or transplantation were initiated when the renal function was approximatelySml/minorless. More recently, Kussman has advocated that transplantation in juvenile diabetics be started earlier, when the serum creatinine approaches 5mg/100ml, in order to avoid irreversible complications.' Whether this approach would decrease the morbidity and mortality in juvenile diabetic nephropathy remains to be proven.

Summary In the light of our experience and that of others, the disheartening results in treating diabetic patients with chronic renal failure as reported in the earl ier days may no longer be considered true. Proper selection of the form of therapy may significantly enhance the survival and well-being of uremic diabetic patients. The results of our series encourage us to continue the active treatment of renal failure due to diabetes and, in general, to recommend transplantation for the juvenile onset group and hemo­dialysis for the adult onset group.

References 1. Kussman J, Goldstein H, and Gleason R: The clinical courseof diabetic

nephropathy, JAMA 236:1861, 1976.

2. Goldstein D and Massry S: Diabetic nephropathy: Clinical course and effect of hemodialysis. Nephron 20:286-296, 1978,

3. BlaggC: Visual and vascular problems in dialyzed patients. Kidney tnt (suppl V 6:S27, 1974,

4. Shapiro F, Leonard A, and Comty C: Mortality, morbidity and re­hab i l i ta t ion results in regular ly d ia lyzed patients w i th diabetes mellitus. Kidney tnt (suppl 1) 6:S8, 1974,

5. Ma K, Masler D, and Brown D: Hemodialysis in diabetic patients with chronic renal failure. Ann Intern Med 83:215, 1975,

6. Najarian J, Sutherland D, Simmons R, Howard R, Kjellstrand C, Mauer S, Kennedy W, Ramsey R, Barbosa J, and Goetz F: Kidney transplanta­tion for the uremic diabetic patient, Surg Gynecol Obstet 144:682, 1977.

7. Simmons R, Kjellstrand C, and Najarian J: Technique, complications and results in transplantation. Transplantation, Najarian J and Simmons R, ed. Philadelphia, Lea and Febiger, 1972, p445.

8. Cutler S and Ederer F: Life table method in analyzing survival, / Chronic Dis 8:611, 1958.

9. Najarian J, Kjellstrand C, and Simmons R: Renal transplantation for diabetic glomerulosclerosis. Ann Surg 178:477, 1973.

10, Mauer S, Barbosa J, and Vernier R: Diabetic vascular lesionsdevelop in normal kidneys transplanted into patients with diabetes mellitus, N Engl I Med 295:196, 1976.

11, Oreopoulous D: Overall experience with peritoneal dialysis. Dialysis Transplant 7:783, 1978.

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