Renal Failure, 20(4), 621-626 (1998)

CLINICAL STUDY

Can Fingernail Creatinine Concentrations Be Used to Predict Duration of Azotemia?

Kamal Sud, 1 MD, DM, Sanjay Maitra, l MD, DM, Madhu Khullar,2 MSC, PhD, Harbir S. Kohli, 1 MD, DM, Vivekanand Jha, MD, DM, Krishan L. Gupta,' MD, DM, and Vinay Sakhuja,1 MD, DM

IDepartment of Nephrology Postgraduate Insfifute of Medical Educatzon and Research Chandigarh, India 2Dqarfrnent of Experimental Medicine Postgraduate Institute of Medical Education and Research Chandigarh, India

ABSTRACT

Clinical use of $fingernail creatinine estimation to predict duration of azoteniia is yet to be validated. We studied the Jingernail creatinine con- centrations in 48 subjects: seven controls, nine with acute renal failure, five with rapidly progressive glomerulonephritis, 12 with chronic renal failure and 15 with end-stage renal failure on maintenance hernodialysis. The creatinine concentration in aqueous eluates of powdered nail clip- pings was determined by the alkaline picrate reaction. The mean jnger- nail creatinine concentration was sigEijcantly higher in patients with chronic renal failure (93.7 f 83.7ug/g;),and end-stage renal disease on maintenance hemodialvsis (118.4 f 46.8 j&g) as compared to those with acute renal failure (36.6 f 23.7pg/g;) and .rapid& progressive glomeru-

Address reprints requests to: Prof. V. SakJmja, Professor and Head, Department of Nephrology, Postgraduate Institute of Medical Education and Resear&, Chandigah, 1600 12 India.

Copyright 0 1998 by Marcel Dekker, Inc.

62 1

www.dekker.com

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622 Sud et al.

lonephritis (35.8 f 20.6,43/@. The creatinine concentrations did not differ significantly between normal subjects (27.2 i 28.7,ug/@ and those with acute renal failure and rapidly progressive glomerulonephritis. However because of large variability in the values offingernail creatinine concen- trations within each group, the test lacked specificity. Therefore, this in- vestigation is an unreliable indicator of duration of azotemia in individual patients and is not likely to be of much clinical use.

Key Words: Acute renal failure; Chronic renal failure; Fingernail cre- atinine.

INTRODUCTION

The management of patients with renal failure of unknown duration centers around the chances of its reversibility. Qute often, especially in developing countries where access to health care is not available to all, patients with chronic renal failure (CRF) present for the first time when they develop symptoms of uremia and have end stage renal disease (ESRD) (1). In these patients, prior or serial renal function tests are not available and nephrologists are called upon to determine the chronicity of renal failure based on the history of azotemic symptoms, the presence of anemia andor hypertension and the assessment of renal size. Unfortunately none of the above parameters is abso- lutely reliable.

In recent years, there has been a renewed interest in using fingemail creatinine con- centrations as a marker of the duration of azotemia. It has been known for over 30 years that measurable amounts of creatinine are present in fingernails and toenails (2). It was postulated that the concentration of creatinine in fingernail and toenail clippings might be of value in distingwshing acute from chronic mmia. If nail creatinine concentfations are a reflection of the blood creatinine concentration at the time the nail was formed, then analysis of creatinine concentrations of the clipped free edge of the nail, which was formed many months earlier, would provide a means of estimating the blood creatinine concentration which was present at that time. This could permit an estimation of dura- tion of azotemia. In support of this hypothesis, Levitt (2) demonstrated that acute renal failure (ARF) patients showed normal fingernail creatinine levels even though their se- rum creatinine was elevated. In contrast, patients with CRF had elevated serum and fin- gernail creatinine concentrations. In addition, after renal transplantation, the fingernail creatinine concentration took approximately 90-120 days to return to normal, despite maintenance of serum creatinine concentrations (Sc,)within the normal range during this period (3). Recently there have been doubts about the clinical utility of this investi- gation (4). The present study was undertaken to reexamine this association and possibly validate this relationship.

MATERIAL AND METHODS

We estimated fingernail creatinine levels in 48 subjects: seven controls, nine with AFW, five with rapidly progressive glomerulonephritis (RPGN), 12 with stable CRF and 15 with ESRD on maintenance hemodialysis. Controls were those without history of any

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Fingernail Creatinine Estimation 623

renal disease or any other chronic ailment. All patients of ARF had an acute and entirely reversible reduction in renal function with no history of renal disease in the p t . Pa- tients who did not have total recovery of renal function on follow-up were excluded. All patients with FWGN had renal biopsy proven crescentic glomerulonqhritis involving more than 50% of the glomeruli sampled. Patients of CRF included those with irre- versible and persistent azotemia of more than 3 months duration with Scr between 3-8 mg/&. Patients with more than 10% increase in Scr over baseline in the previous 4 week period were excluded. Patients with ESRD were on maintenance hemodialysis for at least 4 weeks. Patients less than 18 and more than 65 years of age, pregnant patients and patients with a history of habitual nail biting, psoriasis or peripheral vascular dis- ease were excluded.

Nail clippings were obtained at least 2 hours after the last hand wash from the free edges of all 10 fingernails and the depth of the clippings was at least 1 mm from the: edge of the cuticle. In individuals who wore nail polish, the clippings were obtained at least 48 hours after chemical removal of the polish. These clippings were stored as one sample in plastic bags and analyzed together in one lot (to obtain sufficient material for extraction of creatinine). For preparation, the cuttings were first pulverized to a powder and the powder was weighed and placed in a tube with 5 rnL. of deionised water and tightly stoppered to prevent evaporation. Creatinine was extracted from the powdered nails by gently shalang the tube in a heated water bath for 24 hours at 37°C. Finally the creatinine in the extract was analyzed on an autoanalyzer using the Jaffe's reaction (alkaline picrate method). Values were expressed as pg of creatinine per gram of finger- nails. Nail clippings of all patients and controls were processed and analyzed in one lot.

Statistical Analysis

Student's f test was used to study differences in means. For fingernail creatinine val- ues, Student's f test with unequal variance was used because of non-normal distribution of obtained values andp values less than 0.05 were considered sigmficant.

RESULTS

The clinical characteristics and fingernail creatimne values of patients are as shown in Table 1. Of the nine patients with ARF, four developed renal failure due to hypovolemic ATN, two due to intravascular hemolysis, two after a snake bite and one due to rhabdo- myolysis. CRF patients included four with diabetic nephropathy, four with chroruc glomerulonephritis, three with chronic interstitial nephritis and one with hypertensive nephrosclerosis. Amongst the 15 patients with ESRD, ten had chronic glomeiu- lonephritis, two each had chronic interstitial nephritis and hypertensive glomeruloscle- rosis and one had cast nephropathy secondary to multiple myeloma.

The mean fingernail creatinine concentrations were signrficantly lower in controls (27.2 f 28.7 pg/g) and patients with ARF (36.6 k 23.7 pdg) and RPGN (35.8 f 20.6 pglg) when compared with patients with CRF (93.7 f 83.7 pg/g, p < 0.05) and ESKD (118.4 * 46.8 pg/g, p < 0.001). The fingernail creatinine concentrations &d not differ sigmficantly between controls and those with ARF or RFGN (p > 0.05). The duration, of azotemia was sigdcantly higher in patients with CRF and ESRD as compared to those with ARF and RPGN (p < 0.001). The mean Scr at the time fingemail clippings were

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624 Sud et al.

Table 1

Showing Patient Chamcteristics. Mean Serum Creatinine and Fingemail Creatinine Concentrations

Group Age (years) Males! Known dura- SerUm Fingernail (No. 1 Females tion of renal creatinine creatinine

failure (mg/dL) (Pgk nail)

0.9 +- 0.2 27.2 k 28.7 Controls (7) 32.5 +- 15.8 41 3

ARF (9) 39.0 f 13.8 7i2 10.2 f 5.4 10.1 f 3.7 36.6 f 23.7

RPGN (5) 39.9 f 17.5 312 5.3 f 4.6 8.7 f 3.4 35.8 f 20.6 h Y S

weeks

CRF (12) 45.3 k 12.8 814 17.4 + 17.6 6.0 k 1.3@ 93.7 k 83.7*

ESRD (15) 40.3 f 19.9 1213 17.5 f 19.9 10.5 f 2.8 118.4 f 46.8'

*p < 0.05 when compared with controls, ARF and RPGN 'p < 0.001 when compared with controls, ARF and RF'GM @p > 0.05 when compared with those of ARF, RF'GN and ESRD; ARF: amte renal failure, RF'GN: rapidly progressive renal failure, CRF: chronic renal failure, ESRD: end stage renal disease on mamtenance hemodialysis.

months

months

o w n e d did not differ signrficantly between those with ARF, RPGN, CRF and ESRD (p > 0.05). Considering 50 pg/g concentrations as the upper limit of normal (4), two of seven controls, three of nine patients with ARF and one of five with RPGN had finger- nail creatinine concentrations above the normal range. In addition, five of 12 patients with CRF and one of 15 with ESRD had fingernail concentrations below 50 pg/g (Fig. 1).

DISCUSSION

The differentiation between ARF and CRF in patients who present for the first time with uremia is often difficult. It is not uncommon for nephrologists to be confronted with such a situation when previous medical records are not available. Levltt (2) for the first time suggested that fingernail creatinine concentrations could be used as a marker of duration of amtemia. He found that patients with CRF had higher creatinine concen- trations in the fingernails as compared with controls. Bergamo et al . (3) largely con- firmed the findings of Levitt. Taken together, these studies suggested that the amount of creatinine that enters the fingernail plate during its formation is proportionate to the serum cratinine concentrations at that time. Furthermore it was shown that once the nail is formed, little or no creatinine enters or leaves the nail plate (2, 3).

The results of our study confirm that patients of CRF and ESRD on maintenance hemodialysis have sigmficantly elevated mean fingernail creatinine concentrations as compared to controls and those with ARF. Patients with RPGN had sigtllficantly lower fingernail creatinine values when compared to patients with CRF and ESRD. Fingernail creatinine concentrations of patients with RF'GN were similar to those with ARF and cfid

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Fingernail Creatinine Estimation 625

300

250

- - - m

0 : 200

CONTROLS ARF RPGN CRF ESRD

Figure 1. Showing distribution of fingernail creatine values in different groups

not differ sigmficantly when compared to controls. This can be explained by the slow rate of growth of fingernails in otherwise healthy indwiduals (0.1 mdday) (5). There-, fore it would take around 100 days before the nail grows to a length of 1 cm and is; available for clipping. The patients of RPGN had 5.3 f 4.6 wks of azotemia and there-, fore did not have a long enough period of azotemia to cause an increase in fingernail creatinine concentrations.

However, we also found that there is a large vanability in the values of fingernail creatinine concentrations. Two of seven controls, three of nine patients with ARF and one of five with RPGN had fingernail creatinine concentrations above 50 &g. In add-. tion, five of 12 patients with CRF and one of 15 with ESRD had fingernail concentra-, tions below this level. Therefore, the use of fingernail creatinine concentrations may not be a reliable investigation to assess the duration of azotemia in an in&vidual patient. Similar findmgs were observed by Shand et al. using 50 pg/g as the upper limit of nor- mal (4). Moreover, Levitt also found that three controls had fingernail creatinine con-, centrations above the normal range of 60 pg/g. In addition, three patients of CRF hadl values below this level. The likely explanation of this phenomenon could be the known variability in growth rates of the nails and the method of estimation of nail creatinine concentration (2, 6). The growth rates are higher in children, during pregnancy, in peo-’ ple living in warm climates and in those who practice nail biting (5, 7). In contrast, ag-

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626 Sud et al.

ing, catabolic diseases, immobilization and limb ischemia are associated with slower rates of nail growth (5, 8). In addition, exposure of nails to water can increase the water content of nails and produce erroneous results (3).

In conclusion, the mean fingernail creatinine concentrations are sigmficantly higher in patients with CRF and ESRD as compared to those with ARF and RPGN. The cre- atinine concentrations did not differ significantly between normal subjects and those with ARF and RPGN. However because of large variability in the values of fingernail creatinine concentrations within each group, the test lacks specificity. Therefore, this investigation is an unreliable indtcator of duration of azotemia in an in&vidual patient and is not ldcely to be of much clinical use.

REF’ERENCES

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Chug KS, Jha V Differences in the care of ESRD patients worldwide: Required resources and future out- look. Kidney Int 48 (suppl 50):S7-13, 1995. Levis JI: Creatinine mcmtraticn of human fmgmail and toenail clippin@.. Ann Intern Med 64:312-327, 1966. Bagamo RR, Laidlaw SA, Kopple JD: Fingernail meatinine as a predidor of prior rmal lhdion. Am J Kidney Dis 22:8 14-82 I , 1993. Shand BI, Bailey M.& Bailey RR: Fingernail creatinine concentration as a marker of the duration of renal failure. F’resaaed at the 1 Ith Asian Colloquium in Nephrology, Singapore, 1996. Bean WB: Nail growth-thiiy five years of observations. Arch InternMed 140:73-76, 1980. Van Pilsum JF, Martin RF’, Kit0 E, Mess J: Daermin atim of -tine, meatinme, arginine, guanidinoacetic acid, guanidine and methylguanidine in biological fluid. JBioZ Chem 222:225-236,1956. Dawbex R: Fingernail growth innormal andpsoriatic subjects. BrJDermutol82:454-457,1970. Bean WB: A discourse on nail growth and unusual fmgernails. Trans Am Clln Cbmotd Assoc 74: 1 52-1 67, 1963.

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