Conservative treatment with ketoacid and amino

acid supplemented low-protein diets in chronic

renal failure1
Peter T. Frohling, R. Schmicker, K. Vetter, I. Kaschube, K H. Gotz, M. Jacopian,
and H. Klinkman

ABSTRACT Twenty-six patients with advanced renal failure (glomerular filtration rate < 6
mI/min) were treated with a mixed quality low protein diet and ketoacid analogues. An improve-
ment in nitrogen balance, serum transferrin and phosphate, and base excess was observed after 2
weeks of treatment. In a longer term study, the result of 20 patients treated with ketoacids for up
to 14 months were compared to a group 40 patients who received a low-protein diet with essential

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amino acids. Patients responded similarly to the two diets; however, the group receiving ketoacids
had a significantly lower glomerular filtration rate. There was improvement in calcium and
phosphate metabolism with ketoacid treatment. The patients were able to tolerate treatment with
both the ketoacids and vitamin D. Am. J. Clin. Nutr. 33: 1667-1672, 1980.

Since Walser’ published his results of the acids in patients with advanced renal failure
first successful treatment of chemically who were ingesting a mixed LPD.
uremic patients with ketoacid analogues of
essential amino acids (EAA), other investi- Materials and methods
gators (2-6) have confirmed the beneficial
Twenty-six patients with chronic renal failure were
results of this therapy. Good clinical results
studied. Patients had initially been treated with another
have also been achieved with smaller doses
TABLE 2
Characteristics of patients
TABLE I
Mean daily dosage of EAA and their ketoacid FAA KA
analogues group group

Ketoacid or amino acid Daily intake (g/day) n 40 20

Sex Fl8 Fll
g/day
M22 M9
a-Keto-isoleucine 1.005 43 (20-58)
Age 44 (19-66)
a-Keto-leucine 1.5 15
Diagnosis
a-Keto-phenylalanine 1.020 10 4
GN
a-Keto-vahine 1.290 12
PN 24
a-Keto-methionine 0.890 6 4
CY
L-Lysine acetate 1.580 Glomerular Fihtra- <10 <6
L-Threonine 0.800 tion rate (ml/min)
L-Tryptophan 0.350 Dietary 8.1 (1-25) 12.2 (4-27)
L-Histidine 0.570 pretreatment EAA 6.1 (2-13)
L-Tyrosine 0.450 (n = 14)
(mo)

LPD for an extended period of time. Most of the patients

of keto analogues (KA) as compared with the
had ingested a mixed protein diet substituted with EAA.
doses prescribed by Walser (2, 3, 6). However, The others had received a selective LPD.
the available data are not sufficient to draw Dietary prescription for these patients was changed to
conclusions concerning the optimal quantities
1 From the Academy of Science of the GDR, Central
oftotal nitrogen and individual EAA and KA
Institute of Nutrition Potsdam-Rehbrticke, Research
for uremic patients (7). Our study was de- Clinic of Nutrition; Department ofNephrology, Univer-
signed as a clinical evaluation ofdietary treat- sity ofRostock; St. Josefs Hospital, Potsdam; and Kidney
ment with a mixture of 5 KA and 5 amino Center of Neuruppin, German Democratic Republic.

The American JournalofClinicalNutritwn 33: JULY 1980, pp. 1667-1672. Printed in U.S.A. 1667
 1668 FROHLING ET AL.

a mixed LPD providing 0.4 g of protein per kilogram status. The B vitamins were given. Most patients in both
normal body weight per day. The calorie intake was at groups received vitamin D2 for the prevention of bone
least 35 kcal/kg normal body weight per day. The dose disease (15 mg/week).
of KA was 15 tablets of “Ketosteril” (Fresenius) which Twenty of the 26 patients were followed for 3 months
provided 0.5 g of nitrogen per day (Table 1). The dose or more. The results of this group were compared with
of EAA was 14 tablets of “EAS-Oral” (Fresenius) pro- the data from 40 patients who were treated with an LPD
viding 1.0 g of nitrogen per day. Prescription of alumin- supplemented with EAA as part of a long-term feasabil-
ium hydroxide and calcium citrate was determined ac- ity study. Table 2 gives some of the characteristics of the
cording to the serum phosphorus levels and acid base patients. Patients were monitored with serum urea nitro-
gen, creatinine, calcium, phosphorus and uric acid, base
excess, hemoglobin, transferrin, plasma amino acids, and
TABLE 3
nitrogen balances. Patients were evaluated before begin-
Results of short-term tolerability test
ning treatment with KA, 14 days after initiating treat-
n - 26 Before 0.5 mo ment, and periodically thereafter.
KA- alter KA-
treatment treatment
Results and discussion
BUN 85 77
(mg/dl) SD 23 18
Creatinine x 12.2 12.3
The mean duration of treatment with KA
(mg/dl) SD 2.4 2.7 was 5.2 months (range, 1 to 14 months).
Ratio BUN/creatinine X 7.0 6.4 Eleven patients required dialysis after an av-

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SD 1.5 1.6 erage of 4.5 (1 to 14) months. The mean
Transferrin 204 224
serum creatinine was 19 mg/dl at the initia-
(mg/dh) SD 39 47
Nbahance -1.2 -0.7 tion of dialysis therapy. None of the patients
(g/day) SD 1.2 1.3 showed uremic symptoms. The indication to
Phosphate 5.9 4.7 start dialysis was a hypertensive crisis in one
(mg/dl) SD 1.2 1.2
patient and a decrease in urine flow below
Hemoglobin 5c 9.2 9.1
1.9 1.6 2000 mI/day in the others. One patient died
(&Jdl) SD
Baseexcess x -1.3 +3.1 after 10 months of treatment from septic en-
SD 7.3 6.4 docarditis. Fourteen of 26 patients are under
UricAcid x 8.7 8.8 treatment with KA at the present time, for an
(mg/dl) SD 1.9 2.4
average of 4.5 months (range, I to 9).

( 20)

7
6
BU
S 1 at.

4 40 8

3 6

2 20

0 0.5 3
16 months 0 0.5
F 3 6 months
4

jratio C ) =n
- B UN ‘ creatinine

FIG. 1. Serial serum urea nitrogen, creatine, and the BUN/creatinine ratio in chronically uremic patients
receiving a mixed LPD (0.4 g/kg per day) and either KA or EAA.
 transferrin
mg!dI
transferr in

300

,nn
j range

(.40) (40) (31)

100
- I I #{149} -I
0 0.5 3 6 months

.- #{149}KA a .EAA ( )=n

gN/day

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EIJ KA EAA
FIG. 2. Serial serum transfemin levels and nitrogen balance measurements in chronically uremic patients
prescribed either KA or EAA.

phosphate

mg/dl

9
8
7

4
3

0 0.5 3 6 months 0 0.5 3 6

4 .J-
3 :E
+2
1
base excess
base 1 r
excess

7:
3

a 6 o o.s 3 6
FIG. 3. Serial hemoglobin, serum phosphate, and base excess measurements in chronically uremic patients fed
KA or EAA.

1669
1670 FROHLING ET AL.

Table 3 gives the short term results of the

tolerability with KA for 0.5 months. There
was improvement in nitrogen balance and a .

slight increase in serum transferrin. Base cx- .

cess improved significantly. Blood urea nitro-
gen (BUN) decreased when the initial value
was more than 80 mg/dl. A marked decrease
of phosphate was often observed. 00

Figure 1 shows the serial values for BUN,

creatinine and their ratio in patients receiving
KA or EAA. The BUN was similar with the
two diets even though renal function was
lower in the group receiving KA. Serial serum . . . o

transferrin levels and the nitrogen balance . #{176}

data are illustrated in Figure 2. In both groups

the mean values for serum transferrin were
in the low normal range (Fig. 2). Significantly #{149} ,,.

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higher values for the nitrogen balance were z
found with the EAA diet as compared to the
KA diet after 0.5 months of treatment. The
lower renal function in the KA group and the ...
pretreatment with EAA in most ofthese latter .

patients, however, may account for the dif-

ference in nitrogen balance. At 3 and 6
months there were no differences in nitrogen .

balance between the two groups. diet

Table
4 gives the mean values for EAA in plasma
with the KA and EAA diet therapy. We
found higher values for lysine and threonine . . t,

with KA treatment, but values were still de- . “

creased. The non-EAA were normal in both

groups with the exception of serine.
Serial hemoglobin and phosphate levels
and base excess are shown in Figure 3. Lower , o o ro
values for phosphate were found with KA
treatment even though the amount of phos-
phate binders prescribed had been reduced.
The tendency for negative base excess and, a - r

hence, acidosis, was more evident during the

long term treatment EAA as compared
with
with KA. No significant differences in he-
moglobin concentrations were found in the . r- ri

two groups. 00 C1

The clinical course of one patient during

treatment for 15 months is illustrated in Fig- -
ure 4. The LPD was started when the gb-
merular filtration rate was 3.5 ml/min, and ‘3 ‘ c’ )
after 4 months KA were added. Nitrogen
balance was very negative at the onset of a

treatment with the LPD. Balance became

positive during the nutritional therapy and
was neutral during the long duration of treat- E
ment with KA. Body weight increased by 6
kg during the course of treatment. BUN was
 DIET AND CHRONIC RENAL FAILURE 1671

BUN
PED FAA PED KETO ACIDS

‘160

‘1’IO
A
‘120 L
Y

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3 .5 5

197 4918
a- .BUN
.-------. CREATININE
vzz-7-z7J NITROGEN BALANcE

FIG. 4. Clinical course of one chronically uremic patient fed a selective low-protein potato egg diet (PED), or
diets providing mixed quality protein and either EAA or KA. Arrows indicate the onset of each dietary treatment.

calcium vitamin 0 such observations, Heidland et a!. (6) and

mg/dl
Burns et al. (8) recommended cessation of
with without
vitamin D administration. In the present
(n = 13) (n=7)
study, there was no statistical differences in
serum calcium in these patients receiving vi-
10
tamin D as compared to those who were not
9 (Fig. Mild hypercalcemia
5). was observed in
8 three cases and was reversible when the dose
7 of vitamin D was reduced by half.
6 All patients receiving nutritional treatment
were rehabilitated; some of them returned to
4
full-time jobs. The KA administration was
well tolerated by all patients and gastrointes-
2
tinal side effects were not observed.
The following findings in this study sup-
port the contention that treatment with a
0 0 5 3 months 0 05 3 months
mixed LPD and ketoacids, as indicated in
FIG. 5. Serum calcium values in chronically uremic
patients receiving a KA diet with or without supplemen-
Table 1, provides a number of benefits to the
tal vitamin D2. patients: in a short evaluation of the effec-
tiveness of KA, improvement in nitrogen bal-
lower than 100 mg/dl except when compli- ance, serum transferrin and phosphate, and
cations of infection occurred. Maintenance base excess was observed after patients were
dialysis was started after an episode of infec- administered the ketoacid diet. A comparison
tion because serum creatinine rose to 19 mg/ between EAA- and KA-substituted diets in
dl and urine flow decreased. the longer trials shows that the same thera-
Hypercalcemia has been described as a peutical effects were observed in the KA and
side-effect of treatment with KA. Based on EAA treated patients, even though patients
1672 FROHLING ET AL.

receiving KA had a significantly lower gb- References

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2. RIPPICH, T., N. KArz, A. Mrx AND R. KLUTHE.
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Applikation von Ketoanahogen essentielher Amino-
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mixed LPD (0.4 g/kg per day) is beneficial ketoacids in uremic patients on low-protein diet.
Am. J. Clin. Nutr. 31: 1784, 1978.
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AND S. TALBOT. Comparison of the effects of ke-
conservative therapy. The findings suggest toacid analogues and essential amino acids on nitro-
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