A Surviving Patient with Record High Creatinine

doi:10.4236/ojneph.2013.34037

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Open Journal of Nephrology, 2013, 3, 217-219

Published Online December 2013 (http://www.scirp.org/journal/ojneph)

http://dx.doi.org/10.4236/ojneph.2013.34037

Open Access OJNeph

A Surviving Patient with Record High Creatinine

Andrew C. Storm1, Naing L. Htike2, David A. Cohen3, Robert L. Benz4*

1Department of Internal Medicine, The Johns Hopkins Hospital, Baltimore, USA

2Department of Nephrol ogy, Lankenau Medical Center, Wynnewood, USA

3Department of Internal Medicine, Lankenau Medical Center, Wynnewood, USA

4Division Chief of Nephrology, Lankenau Medical Center and Main Line Health and Lankenau Institute

for Medical Research, Wynnewood, USA

Email: *[email protected]

Received August 24, 2013; revised September 22, 2013; accepted October 20, 2013

which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

ABSTRACT

Creatinine is a product of muscle protein breakdown cleared by the kidneys at a constant rate. The glomerular filtration

rate is estimated based on serum creatinine. There is no definitive lev el of serum creatinine which is itself incompatible

with human survival. We present the highest serum creatinine associated with survival based on a thorough review of

the literature. A 34-year-old male patient with baseline serum creatinine of 1.2 mg/dl presented our emergency depart-

ment with a six week history of new onset of uremic symptoms. His past medical history was unremarkable. On exam,

he was in no distress. His BMI was 28. His exam was significant only for elevated blood pressure and asterixis. His

peak serum creatinine was 53.9 mg/dl. The patient subsequently required maintenance hemodialysis and later changed

to long-term peritoneal dialysis. To our knowledge, based on a thorough review of the literature using PubMed, Coch-

rane Database and the United States Renal Data System (USRDS), this is the highest level of serum creatinine ever re-

ported. We conclude that serum creatinine itself is non-lethal. It is more likely that other electrolyte and retained meta-

bolic abnormalities of renal failure frequently cause symptoms or death before creatinine toxicity, if such a level exists,

creatinine has reached.

Keywords: Survival; Outcome; Uremia; Mortality; Creatinine

1. Introduction

Creatinine is the product of dephosphorylation of crea-

tine phosphate during muscle contraction and is freely

filtered and normally also secreted via the proximal tu-

bules and excreted by the kidneys [1-4]. Thus, creatinine

clearance exceeds glomerular filtration rate by the

amount or percent of creatinine secretion. The serum

creatinine level is relatively co nstan t and its valu e is used

to estimate glomerular filtration rate (eGFR) [5]. The

normal reference range for serum creatinine is 0.7 to 1.3

mg/dL (62 - 115 umol/L) for men and 0.6 to 1.1 mg/dL

(53 - 97 umol/L) for women [3]. Although creatinine is

often assumed to be one of the uremic toxins, very little

data are available on its adverse effects on human physi-

ology [6]. One animal study reported that creatinine in-

jection reduced survival time in anephric rats [7]. A ca-

nine study showed gastrointestinal side effects of chronic

creatinine intoxication [8]. The authors did not receive

funding or support for this case study.

2. Case Presentation

A 34-year-old man with a baseline creatinine 1.2 mg/dl

in 2003 and no significant pa st medical history presented

to the Lankenau Medical Center Emergency Department

with complaints of nausea, vomiting and diarrhea over

the prior six weeks. These symptoms, in addition to

30-pound weight loss, led to the patient’s hospital admis-

sion. He also reported intermittent ankle swelling and

nocturia two to three times nightly. He denied dysuria,

hematuria, foamy urine or seizure.

Past medical history included cervical radiculopathy in

the distant past. He denied any childhood kidney disease

or recurrent urinary tract infections. There was no history

of hypertension. He did not take non-steroidal an-

ti-inflammation drugs. He occasionally used mail-order

herbal colonic cleansers. The patient denied tobacco,

alcohol, and drug abuse. Family history was significant

for diabetes, hypertension and COPD in his mother. His

*Corresponding author.

A. C. STORM ET AL.

218

father died of prostate cancer. He denied any family his-

tory of kidney disease or autoimmune disease.

On exam he appeared to be in no acute distress. His

body mass index was 28. His vital signs were normal

except blood pressure 184/93. His oxygen saturation was

100% on room air. Neurological exam revealed asterixis.

There was no uremic frost and the remainder of the

physical examination was unremarkable.

The urinalysis showed a specific gravity of 1.016, pH

6.5, with 3 plus proteinuria and positive for red blood

cells and leukocytes, too numerous to count. No casts or

crystals were detected. His urine protein to creatinine

ratio showed 6.2 grams of proteinuria. The serum potas-

sium was 5.6 mEq/L, BUN 135 mg/dL and creatinine 51

mg/dL. The latter was confirmed by dilution method and

rose to 53 mg/dl prior to initiation of hemodialysis. Cal-

culated eGFR was 1 ml/min. Further tests showed mi-

crocytic iron deficiency anemia, hyperphosphatemia,

hypocalcaemia and secondary hyperparathyroidism. His

arterial pH was 7.33. He had a weakly positive cANCA,

which was likely not clinically significant. Detailed la-

boratory values are shown in Table 1.

Renal ultrasoun d showed an atrophic right kidney (6.8

cm) and a normal to slightly small sized left kidney (9.8

cm) with cortical hyper echogenicity. There was no hy-

dronephrosis, cystic kidney disease or nephrocalcinosis.

His chest X-ray was unremarkable.

An internal jugular venous hemodialysis catheter was

placed and hemodialysis was initiated on the day of ad-

mission. He was discharged 9 days later after being set

up for outpatient maintenance hemodialysis. At the time

of hospital discharge, his creatinine was down to 12.7

mg/dl with the help of hemodialysis. The patient subse-

quently changed modality to long term peritoneal dialysis

and was doing well on follow up examination 6 months

after discharge.

3. Discussion

Creatine is a dietary non-essential amino acid which is

phosphorylated by the enzyme creatine kinase in the liver,

pancreas and kidney. Creatine phosphate is then released

into the blood stream and is stored by organs such as the

brain and muscle for growth, tissue repair and other en-

ergy dependent activities [1,3]. In muscle, dephosphory-

lation of creatine releases energy required for muscle

contraction [3,4]. Approximately 1 to 2 percent of free

creatine in muscle irreversibly and spontaneously con-

verts to creatinine which in turn is released into the blood

stream and freely filtered, secreted and excreted by the

kidneys [2,3].

Serum creatinine level is commonly used as an indi-

cator of the kidney function. Although it is a marker of

uremic toxicity, the actual effect o f creatinine on homeo-

stasis in humans is unresolved. In fact, higher creati-

Table 1. Extended Laboratory Data.

Lab Reference Patient Value

Sodium 136 - 144 mEq/l 136

Potassium 3.6 - 5.1 mEq/l 5.6

Chloride 98 - 109 mEq/l 96

Carbon Dioxide 22 - 32 mEq/l 17

Glucose 70 - 99 mEq/l 96

BUN 8 - 20 mg/dl 135

Creatinine 0.8 - 1.3 mg/dl 51.0

Calcium 8.9 - 10.3 mg/dl 7.7

Phosphorous 2.4 - 4.7 mg/dl 15.7

Protein, total 6.0 - 8.2 g/dl 8.2

Albumin 3.4 - 5.0 g/dl 3.7

AST 15 - 41 u/l 6

ALT 16 - 63 u/l 8

CPK 16 - 300 u/l 431

PTH, intact 2 12 - 88 pg/ml 1187.2

pH 7.35 - 7.45 7.33

PCO2 35 - 48 mmHg 31.0

PO2 83 - 100 mmHg 114

WBC count 4.5 - 10.8 K/ul 7.7

Hemoglobin 14.0 - 17.5 g/dl 5.6

MCV 83 - 97 fl 80.9

Platelet 150 - 400 k/ul 34 3

PT 12.3 - 14.9 sec 17.5

PTT 24 - 36 sec 38

Glomerular BM Ab<1.0 <1.0

Antistreptolysin O<117 IU/ml 30

Hep B Surface Ag Nonreactive

ANA <1:40 Nonreactive

C-ANCA Negative

Positive, 1:20

P-ANCA Negative Negative

HIV 1&2 Negative Negative

nine values at presentation with end stage renal disease

have been shown in a study of over 5000 patients to cor-

relate with incr eased survival possibly because it is a mar-

ker of functional status and muscle mass in a given pa-

tient [9]. Animal studies generally conclude that create-

nine toxicity in and of itself is not a major factor in ure-

mic toxicity. However, Levine, et al. reported creatinine

injections to the nephrectomized rats reduced lifespan by

two days when compared to nephrectomized rats injected

with water alone. This study concluded that creatinine

reduced survival dose-dependently [7]. Canines chroni-

cally “intoxicated” with creatinine to an average serum

concentration of 38 mg/dl, was associated with gastro-

duodenitis and mild anemia [8].

Open Access OJNeph

A. C. STORM ET AL.

Open Access OJNeph

219

A literature search of PubMed, Cochrane Reviews, and

the United States Renal Data System (USRDS) failed to

reveal case reports or data sets with a creatinine level as

high as our patient. The USRDS records show that over

the past 15 years, less than only 1.28% of all new ESRD

cases have a reported initial creatinine over 20 mg/dl [10 ].

Their data also include no values over 30 mg/dl indicat-

ing that the reported case herein could be the highest

createnine (53 mg/dl) in the literature. Despite this re-

cording the high level, the patient’s functional status and

clinical outcome were remarkably stable out of propor-

tion to the chemical evidence of his azotemia. It is possi-

ble that this patient has a chronic single functioning kid-

ney which was affected by either essential hypertension

or chronic glomerulopathy. More likely, he may have

focal and segmental glomerulosclerosis related to a small

kidney and chronic hyperfiltration. However, renal bi-

opsy was contraindicated due to advanced and irreversi-

ble nature of the kidney disease and the presence of a

single functio n i ng ki d ney .

In summary, we report what appears to be the highest

recorded serum creatinine in a surviving uremic patient.

This finding implies that creatinine itself may h ave a mi-

nimally pathophysiologic effect on uremic patients.

REFERENCES

[1] N. V. Bhagavan, “Protein and Amino Acid Metabolism,”

In: J. Hayhurst, Ed., Medical Biochemistry, Harcourt/

Academic Press, Burlington, 2002, pp. 331-332.

[2] D. J. Newman and C. P. Price, “Nonprotein Nitrogen Me-

tabolites,” In: C. A. Burtis and E. R. Ashwood, Eds., Ti-

etz Fundamentals of Clinical Chemistry, W.B. Saunders

Company, Philadelphia, 2001, pp. 414-422.

[3] J. M. Watras, “Berne & Levy Physiology,” 6th Edition.

Mosy, Inc., Santa Clara, 2008, pp. 246-247.

[4] G. C. Curhan and W. E. Mitch, “Brenner & Rector’s The

Kidney,” 8th Edition. Saunders, Philadelphia, 2008, pp.

1826-1827.

[5] A. S. Levey, T. Greene, J. W. Kusek, G. J. Beck and

MDRD Study Group, “A Simplified Equation to Predict

Glomerular Fi ltrat ion Rate from Serum Cre ati nine,” Jour-

nal of the American Society of Nephrology, Vol. 11. Suppl.

2, 2000, p. 155.

[6] A. Yavuz, C. Tetta, F. F. Ersoy, V. D’intini, et al., “Ure-

mic Toxins: A New Focus on an Old Subject,” Seminars

in Dialysis, Vol. 18, No. 3, 2005, pp. 203-211.

http://dx.doi.org/10.1111/j.1525-139X.2005.18313.x

[7] S. Levine and A. Saltzman, “Are Urea and Creatinine

Uremic Toxins in the Rat?” Renal Failure, Vol. 23, No. 1,

2001, pp. 53-59.

http://dx.doi.org/10.1081/JDI-100001283

[8] S. Giovannetti, M. Biagini, P. L. Balestri, R. Navalesi, P.

Giagnoni, A. De Matteis, P. Ferro-Milone and C. Perfetti,

“Uraemia-Like Syndrome in Dogs Chronically Intoxi-

cated with Methyl Guanidine and Creatinine,” Clinical

Science, Vol. 36, No. 3, 1969, pp. 445-452.

[9] J. C. Fink, R. A. Burdick, S. J. Kurth, S. A. Blahut, N. C.

Armistead, M. S. Turner, L. M. Shickle and P. D. Light,

“Significance of Serum Creatinine Values in New End-

Stage Renal Disease Patients,” American Journal of Kid-

ney Diseases, Vol. 34, No. 4, 1999, pp. 694-701.

http://dx.doi.org/10.1016/S0272-6386(99)70395-1

[10] US Renal Data System. USRDS 1995-2010 Data Report:

Atlas of End-Stage Renal Disease in the United States.

http://www.usrds.org/2010/view

Abbreviations

eGFR: estimate glomerular filtration rate.

COPD: chronic obstructive pulmonary disease.

USRDS: United States Renal Data System.

ESRD: End stage renal disease.

BUN: Blood urea nitrogen.

AST and ALT : liver enz y mes.

CPK: creatinine kinase.

PTH: parathyroid hormone.

ANA: anti-nuclear antibody.

ANCA: anti-neutrophil cytoplasmic antibodies.

BMI: body mass index.