Saudi Journal of Kidney Diseases and Transplantation

: 2007  |  Volume : 18  |  Issue : 4  |  Page : 551--555

Correlation Between Creatinine Clearance and Transtubular Potassium Concentration Gradient in Old People and Chronic Renal Disease Patients

Carlos Musso1, Vassilis Liakopoulos2, Ioanis Stefanidis2, Raul De Miguel3, Nora Imperiali1, Luis Algranati1,  
1 Nephrology Deparment, Hospital Italiano de Buenos Aires, Argentina
2 Nephrology Department, Larissa, Greece
3 Laboratory Deparment, Hospital Italiano de Buenos Aires, Argentina

Correspondence Address:
Carlos Musso
Nephrology Department, Hospital Italiano de Buenos Aires, Buenos Aires


Senescence and chronic kidney disease (CKD) reduce progressively glomerular filtration rate (GFR), which usually results in an increase in potassium renal secretion. To evaluate whether the transtubular potassium concentration gradient (TTKG) is more accurate parameter for evaluating the renal secretion of this cation than using fractional excretion of potassium as its urinary secretion marker, we studied 55 subjects, 43 of them were healthy elderly volunteers and 12 were CKD patients. Exclusion criteria were: abnormal plasma potassium level or presence of any disease or drug that could induce alteration of balance of this electrolyte levels. All the subjects were on a diet with a potassium content around 50 mmol/day. The curves, which demonstrate the relationship between creatinine clearance and TTKG and the grade of correlation between these two parameters were analyzed in both groups. We found that the transtubular potassium concentration gradient had a significant negative correlation with the creatinine clearance level in the healthy elderly group, while there was no correlation in the CKD group.

How to cite this article:
Musso C, Liakopoulos V, Stefanidis I, De Miguel R, Imperiali N, Algranati L. Correlation Between Creatinine Clearance and Transtubular Potassium Concentration Gradient in Old People and Chronic Renal Disease Patients.Saudi J Kidney Dis Transpl 2007;18:551-555

How to cite this URL:
Musso C, Liakopoulos V, Stefanidis I, De Miguel R, Imperiali N, Algranati L. Correlation Between Creatinine Clearance and Transtubular Potassium Concentration Gradient in Old People and Chronic Renal Disease Patients. Saudi J Kidney Dis Transpl [serial online] 2007 [cited 2020 Dec 2 ];18:551-555
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Senescence process and chronic kidney disease (CKD) can cause a progressive reduc­tion glomerular filtration rate (GFR),which results in an increase in urinary potassium excretion to larger extent in the chronically diseased than in the aged kidneys. [1],[2]

Correlating curves between creatinine clea­rance CrCl and fractional excretion of potassium have already been described in the old and CKD individuals. [3],[4],[5] These curves are usually used in clinical practice to evaluate whether hyperkalemia is due to an inadequate renal potassium secretion or not, since a urinary potassium excretion lower than ex­pected means an inadequate renal potassium secretion. The expected values are esta­blished in each group by these curves. [6]

Since distal potassium secretion and water reabsorption occur both in the collecting tubules, fractional excretion of potassium is a less accurate index evaluating distal pota­ssium secretion because the effect of water excretion is not accounted for by this index. Conversely, the transtubular potassium con­centration gradient (TTKG), which is an index of potassium secretory activity in the collecting tubules, may better correlate with the urinary potassium and water handling at this nephron segment.[7],[8]

We aim of this study to evaluate the corre­lation between the TTKG and the CrCl in CKD and healthy aged individuals, and to establish the curves that represent such corre­lation, since such curves have not yet been described in any of these groups.

 Materials and Methods

A total of 55 individuals were studied, 12 of them were patients with CKD and 43 were healthy elderly subjects. Informed consent was obtained from each volunteer.

Exclusion criteria in both groups were the presence of abnormal plasma potassium level, diabetes mellitus, cardiac failure, cirrhosis, obstructive uropathy, or medical prescription based on any medication that could alter the potassium balance: beta blockers, calcium channel blockers, non­steroidal anti-inflammatory drugs, glucocor­ticoids, mineralocorticoids, digoxin, diuretics, insulin, oral hypoglicemic agents, ion ex­change resins, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, and potassium sparing agents. Additional exclu­sion criteria for the group of the healthy elderly individuals included:

1. Presence of nephropathy: ruled out by normal blood and urine analysis and also normal renal ultrasound imaging

2. Age under 65 years

Inclusion criteria for the CKD group was:

1. Presence of chronic non-obstructive renal insufficiency documented by medical record, previous blood and urine analysis, and renal ultrasound

2. Pre-dialysis CKD patients

All subjects of the study were on a diet containing 50 mmol of potassium daily , and intake was documented by a three-day dietary record. Plasma potassium (K + , creatinine, urea, glucose and osmolality, besides height and weight were measured. Then, we estimated 24-hour CrCl and TTKG in each patient according to the following formulas:

-CrCl: urine creatinine (mg/dl) x 24-hour urine volume (ml)/plasma creatinine (mg/dl) x 1440 [9]

-TTKG = (K + ) urine/(urine/plasma)osm/(K + ) plasma [7]

All the TTKG indices were obtained from non-low osmolality fasting urine samples (after nine hours of water restriction). The curves that correlate the relationship between CrCl and TTKG were obtained from all the study individuals.

 Statistical analysis

Main clinical and biochemical parameters were compared between both study groups by Student's t test. Afterwards, the correlation between the CrCl and TTKG in each group was analyzed applying Spearman's correlation test.


The individuals in the elderly group were healthy with age that ranged from 65-103 years (mean age 76±9 years old). Their mean CrCl and TTKG were 62±23ml/min and 4.2±1.9 respectively. The CKD group had an average age of 65±16 years (range 45-80) and their CrCl and TTKG were 39±22 ml/min and 6.2±1.8 respectively.

Age, height, plasma sodium, urea and crea­tinine, urinary sodium, creatinine and osmo­lality as well as CrCl were significantly different between the two groups, [Table 1]. Increased plasma urea and creatinine, and reduced urine creatinine and CrCl in the CRD people can be explained by their impaired renal function.

Plasma osmolality was not significantly different between the two groups, even though the plasma urea level was signifi­cantly higher in the CKD group. No signi­ficant difference was observed between the two groups regarding the components of the TTKG formula, except for the urinary osmolality, which was lower in the CKD group, [Table 1].

We constructed a curve correlating the TTKG value with CrCl in CKD and healthy elderly individuals, [Figure 1]. Then we ana­lyzed whether there was a significant corre­lation between CrCl and TTKG in each group finding only a significant (negative) corre­lation in the elderly group, [Table 2].


In CKD patients, as the glomerular filtra­tion falls the fractional excretion of potassium increases. This is one of the mechanisms that prevents patients from developing hyperkalemia even at GFR of 5 ml/min. This phenomenon is the result of a prog­ressive increase in serum potassium that stimulates an augment in a plasma aldosterone level and consequently a greater renal potassium secretion. [2] Senecence process is associated with a progressive reduction in GFR that results in an increase in potassium renal secretion. However, this potassium secretion is lower than that observed in CKD patients. [1] We could in establish in this study the correlation curves between CrCl and TTKG in the elderly individuals and CKD patients using TTKG as urinary potassium secretion marker. [3],[4],[5] Interestingly, we did not find statistical differences in most components of the TTKG formula between the two study groups. Only urine osmolality was significantly lower in the CKD group than the elderly individuals. Based on these data, it seems that the difference in urinary osmolality is responsible for the difference in TTKG values between the two groups which reflects more impaired water reabsorption capability in the CKD patients than the elderly individuals.

Since urinary osmolality is an important component of the TTKG formula, and urinary concentration capability is deeply impaired in chronic renal disease patients, this could explain the lack of correlation between TTKG and CrCl in this renal disease group justifying the possible inaccu­racy of this index in CKD patients. Con­versely, the less impaired water concentration capability in the healthy elderly individuals could explain the significant correlation between the CrCl and TTKG in this group.

We conclude that our study suggests that transtubular potassium concentration gradient curve showed a significant negative corre­lation with creatinine clearance in the elderly healthy individuals, while no correlation between these two variables was observed in the chronic renal disease patients.


The authors wish to thank the Epide­miology Division of the Internal Medicine Department - Hospital Italiano de Buenos Aires for its help in the statistical analysis of this study.


1De Toro Casado R, Macias-Nunez JF. Physiological Characteristics of the renal ageing: clinical consequences. Anales de Medicina Interna 1995;12:157-9.
2Swartz R. Fluid, electrolyte, and acid-base changes during renal failure. In: Kokko J, Tannen R, editors. Fluids and electrolytes. Philadelphia: W.B.Saunders; 1996. p. 487-­500.
3Hene RJ, Boer P, Koomans HA, Mees EJ. Plasma aldosterone concentrations in chronic renal disease. Kidney Int 1982;21: 98-101.
4Musso CG, Miguel R, Algranati L, Farias E. Renal potassium excretion comparison between chronic renal disease patienta and old people. Int Urol Neprol 2005;37:167-70.
5Musso CG, Fainstein I, Kaplan R, Macias Nunez JF. Tubular renal function in the oldest old. Rev Esp Geriatr Gerontol 2004; 39:314-9.
6Rose B, Post T. Hiperpotasemia. In: Rose B, Post T, eds). Transtornos electrolytos y del equilibrio acido-base. Madrid: Marban; 2002. p. 898.
7Halperin M, Goldstein M. Potassium physio­logy. In: Halperin M, Goldstein M, eds. Fluid, electrolyte, and acid-base physiology. Philadelphia: Saunders; 1999. p. 390-3.
8Ethier JH, Kamel KS, Magner PO, Lemann J, Halperin ML. The transtubular potassium concentration in patients with hypokalemia and hyperkalemia. Am J Kidney Dis 1990;4:309-15.
9Vander A. Renal clearance. In: Vander A, ed. Renal physiology. Mexico: Inter­americana; 1993. p. 42-50.