Manuel Vilas

Creatinine reabsorption by the aged kidney

AimThe handling of renal creatinine in human beings has classically been described as the result of two particular physiological processes: glomerular filtration and proximal tubular secretion. However, there are particular physiological situations in which tubular creatinine reabsorption has been documented, such as in the case of healthy newborns and premature babies. We performed a prospective study in order to evaluate if there is tubular creatinine reabsorption in healthy elderly people.Patients and methodWe studied prospectively nine healthy volunteers, four of them young (20–33xa0years old) and the remaining five, old (65–73xa0years old). Since creatinine is secreted in the proximal tubules, and its secretion can be completely blocked by cimetidine administration, a creatinine clearance with cimetidine reliably represents the glomerular filtration rate. Therefore, if the ratio creatinine clearance (Ccr)/creatinine clearance with cimetidine (CcrWC) is higher than one, this would indicate net creatinine secretion, whereas a ratio lower than one would indicate a net renal creatinine tubular reabsorption; a ratio equal to one indicates creatinine filtration. Finally, the Ccr, CcrWC, and Ccr/CcrWC ratios were compared between the young and old group.Statistical testsMann-Whitney and Wilcoxon tests were used.ResultsAs expected, creatinine clearance in the elderly was significantly lower than in the young [Ccr: 74.4xa0ml/min (47.9–100.9) (old) vs. 153.8xa0ml/min (108.3–199.2) (young), pxa0=xa00.014]. Similarly, the creatinine clearance with cimetidine (CcrWC) was significantly lower in the elderly compared to the young [CcrWC: 81.8xa0ml/min (69.2–94.5) (old) vs. 122.5xa0ml/min (82.6–162.4) (young), pxa0=xa00.028]. The ratio of Ccr/CcrWC was 0.9 in the elderly vs. 1.26 in the young (pxa0=xa00.014), indicating net creatinine reabsorption in the elderly and net creatinine secretion in the young.ConclusionOur findings indicate that there seems to be a net reabsorption of creatinine in the renal tubules of healthy old persons.

Fractional excretion of K, Na and Cl following furosemide infusion in healthy, young and very old people.

Furosemide test is a simple and useful test of renal physiology used to evaluate the capability of the collecting ducts to secrete potassium under the effect of serum aldosterone. Its behaviour pattern has been established in children and young adults but not described in very old healthy people, which we explored in this study.Material and methodsTwenty-six healthy volunteers on a standard Western diet (50xa0mmol of K/day) were studied: 20 of them were young (between 17 and 40xa0years old) and the rest were very old (between 75 and 85xa0years old). They suffered from no diseases and were not on any medication. Before, during the test and 180xa0min after a single dose of intravenous furosemide (1xa0mg/kg), urine and blood samples were obtained for creatinine and electrolytes levels. From these data we calculated fractional excretion (FE) of electrolytes; serum aldosterone was measured pre and post furosemide infusion. Statistical analysis was performed by applying Student’s t-test.ResultsThere was no significant difference regarding pre-furosemide (basal) FE of potassium between the very old and young group. Post-furosemide average FE of potassium was significantly lower in the very old group (27.4xa0±xa02%) compared with the young group (35.4xa0±xa09%) (Pxa0=xa00.04). Even though there was no significant difference in post-furosemide peak FE of potassium value, it was reached later in the very old (120xa0min) compared with the young (30xa0min). Serum aldosterone levels were significantly higher post furosemide in both groups: 18.3xa0±xa012.2xa0ng/dl (pre) versus 32.5xa0±xa018.6xa0ng/dl (post) in the young (Pxa0=xa00.007) and 69.8xa0±xa013.7xa0ng/dl (pre) versus 113.3xa0±xa054.8xa0ng/dl (post) in the very old (Pxa0=xa00.04). Furthermore, all serum aldosterone values (pre and post furosemide) were significantly higher in very old people compared with young people (Pxa0<xa00.001). Basal fractional excretion of sodium and chloride were slightly higher in the very old group compared with the young group (Pxa0=xa00.05). Average post-furosemide FE of sodium and chloride were slightly and significantly lower in the very old (Pxa0=xa00.05 and Pxa0=xa00.03), respectively. However, there was no significant difference in peak post-furosemide FE of sodium and chloride values, which were reached later in the very old (120xa0min) compared with the young (30xa0min).ConclusionFurosemide test showed a significantly lower average post-furosemide FE of potassium value, delayed post-furosemide peak FE of Na, K and Cl and a hormonal pattern of aldosterone resistance in very old people.

Renal reserve in the oldest old

IntroductionDecline in glomerular filtration rate (GFR) is one of several changes in renal physiology in the elderly. Renal reserve (RR) is the kidney′s capacity to increase its basal GFR by at least 20% after a protein overload. Even though it has already been reported that RR is preserved in healthy old people, there is no information whether RR is also preserved in the healthy very old one (older than 74 of age), which we decided to study and report our findings in this paper.Material and methodWe studied RR in 16 healthy persons divided into three age groups: young: 20–40xa0years old (n: 5): 64–74xa0years old (n: 6) and oldest old: >74xa0years old (n: 5). Renal reserve test was performed by assessing creatinine clearance with cimetidine before and after an oral protein load. Statistical analysis was performed using ANOVA test.ResultsEven though renal reserve response was present in all age groups, its magnitude (delta GFR) was significantly higher in the healthy young group (103.6xa0±xa053xa0ml/min) compared to the old one (34.1xa0±xa040xa0ml/min) (Pxa0=xa00.002), while it was significantly lower in the healthy oldest old (20.7xa0±xa00.7xa0ml/min) group compared to the other two groups (Pxa0=xa00.002).ConclusionRenal reserve is preserved in healthy very old people, but its magnitude decreases significantly with age.

Renal creatinine handling in very old patients with chronic renal disease

Renal creatinine handling is basically the result of its glomerular filtration and proximal tubular secretion. However, creatinine reabsorption has been documented in certain conditions, such as premature babies, newborns, and healthy elderly people. Additionally, it is known that there is an increase in the proportion of secreted creatinine in chronic renal disease. In this paper, we report our studies on the characteristic reabsorption pattern of creatinine in the elderly with chronic renal disease.Material & MethodWe studied twenty-seven volunteers with chronic kidney disease, eleven of whom were young and the rest were very old (age >75xa0years old). We measured creatinine clearance without (Ccr) and with cimetidine (CcrWC) and Ccr/CcrWC ratio from each volunteer, in timed urine samples. Then, Ccr, CcrWC, and Ccr/CcrWC ratio were compared between young and very old people in two chronic kidney disease subgroups: stages II–III and stages IV–V. Statistical analysis was performed applying a non-parametric test (Wilcoxon).ResultsWe observed a tendency towards a lower Ccr/CcrWC ratio in the very old stage II–III group compared with the young one: 1 (0.96–1.26) (very old) vs 1.3 (1.1–1.5) (young), Pxa0=xa00.09, on the contrary, there was no significant difference in Ccr/CcrWC ratio between very old and young person with stage IV–V CKD: 1.66 (1.41–2.21) (young) vs 1.77 (1.1–2.7) (young), Pxa0=xa0NS.ConclusionCreatinine secretion pattern in very old patients with advanced chronic renal disease is similar to that observed in young ones with similar level of CKD.

Renal calcium, phosphorus, magnesium and uric acid handling: comparison between stage III chronic kidney disease patients and healthy oldest old

IntroductionIt is known that chronic kidney disease (CKD) and senescence bring about a progressive reduction in glomerular filtration rate (GFR) and that in the former this is usually associated with an increase in the fractional excretion of calcium, phosphorus, magnesium, and uric acid. However, it has not yet been explained how these substances are excreted in the healthy oldest old. Thus, in the present study, we examined the renal handling of these substances in very aged people in comparison with CKD patients with similar GFR levels (stage III—CKD).Materials and methodsTwenty volunteers were studied; 10 of them were healthy very old (VO) (≥75xa0years old) individuals and 10 were stage III CKD patients. Exclusion criteria were as follows: presence of altered (abnormally high or low) plasma calcium, phosphorus, magnesium and uric acid, as well as previous diagnoses of diabetes mellitus and obstructive uropathy and use of drugs that could alter plasma levels of the studied substances. All volunteers were on a diet with the same content of these elements (3-day dietary register). We measured calcium, phosphorus, magnesium, uric acid, creatinine in serum plasma and morning urine, as well as serum parathyroid hormone level, in each volunteer. From these data, fractional excretion (FE) of these substances was obtained. A statistical analysis was carried out using the Wilcoxon test.ResultsSerum creatinine: 1.8xa0±xa00.4xa0mg/dl (CKD) versus 0.8xa0±xa00.2xa0mg/dl (VO), pxa0=xa00.0002; serum calcium: 9.1xa0±xa00.3xa0mg/dl (CKD) versus 8.7xa0±xa00.4 (VO), pxa0=xa00.022; serum magnesium: 2.3xa0±xa00.2xa0mg/dl (CKD) versus 2.0xa0±xa00.1 (VO), pxa0=xa00.05; serum phosphorus: 3.9xa0±xa00.5xa0mg/dl (CKD) versus 3.0xa0±xa00.4xa0mg/dl (VO), pxa0=xa00.002; serum uric acid: 6.6xa0±xa01.5 (CKD) versus 5.2xa0±xa01.4xa0mg/dl (VO), pxa0=xa00.04; FE of calcium: 2.5xa0±xa01xa0% (CKD) versus 0.8xa0±xa00.3xa0% (VO), pxa0=xa00.04; FE of magnesium: 7.2xa0±xa04.1xa0% (CKD) versus 2.9xa0±xa00.9xa0% (VO), pxa0=xa00.02; FE of phosphorus: 25xa0±xa09xa0% (CKD) versus 9.1xa0±xa05.7(VO), pxa0=xa00.001; FE of uric acid: 10xa0±xa03xa0% (CKD) versus 8xa0±xa05xa0% (VO), pxa0=xa00.05.ConclusionSerum levels and FE of calcium, phosphorus, magnesium and uric acid were significantly higher in CKD patients compared to healthy very old people with similar GFR, except for serum magnesium and FE of uric acid, which were similar in both groups.

Nephroprevention in the oldest old with chronic kidney disease: Special considerations

Nephroprevention strategies are crucial for handling chronic kidney disease (CKD) complications, and slowing its progression. However, these preventative measures should be guided by major geriatrics principles in order to help nephrologists to adequately handle the oldest old with CKD. These geriatric concepts consist of taking into account the relevance of choosing an individualized therapy, handling clinical frailty, and keeping a geriatric perspective which means that a good quality of life is sometimes a more important therapeutic objective in octogenarians than merely prolonging life. Even though nephroprevention strategies for treating the oldest old with CKD are basically similar to those applied to younger patients such as low sodium and protein diet, optimized hemoglobin levels, blood pressure and metabolic control, the treating physician or care provider must at all times be ready to make fundamental adjustments and tweak patient care paradigms and objectives if and when the initial therapeutic options applied have caused unintended clinical consequences and complications. Additionally, the sarcopenia status should also be evaluated and treated in very old CKD patients.

Evaluation of HUGE equation (hematocrit, urea, gender) performance for screening chronic kidney disease in clinically stable cirrhotic patients

for HUGE equation validation patient’s evaluation by two nephrologists blind between them, as gold standard for renal health status, was used [3–5]. CKD is an entity frequently diagnosed in cirrhotic patients, and this kidney–liver alteration may be caused by diseases that can affect both organs (e.g., chronic virus C infection with cryoglobulinemia), or renal conditions induced by cirrhosis (e.g., Ig A nephropathy or pre-renal insufficiency induced by an increased vasomotor tone on renal circulation [6]. An equation like HUGE could be useful for screening CKD in cirrhotic patients, but this equation is based on serum parameters that can be altered by cirrhosis: Hematocrit may be low due to erythropoietin resistance (chronic disease anemia), and serum urea values may be lower because of a reduced urea biosynthesis (reduced hepatic conversion of ammonium to urea) [7, 8]. Thus, we decided to originally evaluate whether HUGE equation could be an accurate tool for detecting CKD in stable cirrhotic patients despite the influence that this condition can have on its constituents. With this objective, we performed a retrospective observational study to assess the operational characteristics of HUGE equation for screening CKD in 75 patients suffering from stable liver cirrhosis (Child–Pugh A) mostly secondary to hepatitis C (43 %), selected from a population of 750 cirrhotic patients who were on follow-up during 1 year (January 2014–January 2015) by the Hepatology and Transplantation Section of the Internal Medicine Division in the Hospital Italiano de Buenos Aires (Argentina). Inclusion criteria were as follows: to have information, every 4 months, during the year of the study (2014–2015) regarding patients’ serum and urine electrolytes, urea, creatinine, uric acid, hematocrit, hemoglobin, glucose, intact parathyroid hormone, urinalysis, and renal ultrasound. Editor,

Proximal Tubule Function and Free Water Clearance: Comparisonbetween Healthy Elderly and Young HIV+ Patients

In previous studies it was documented that proximal tubule sodium reabsorption capability was preserved in healthy elderly, while Thick Ascending Loop of Henle (TALH) one was reduced. Aim: Since, it has also been documented that senile changes are accelerated in HIV patients, we performed a prospective study in order to evaluate if there was a significant difference in proximal and TALH function between healthy elderly and HIV patients. Methods: Proximal and TALH was analyzed by performing hyposaline infusion test in 10 young (≥ 18-≤ 40 years old) HIV volunteers under treatment with tenofovir, free of viral charge, and normal renal function: serum creatinine, urinary sediment, and renal ultrasound), with the control group made up of 10 healthy old volunteers (≥ 65 years old). Results: During the test, it was observed that the HIV group had a significant reduction of natremia (HIV: 133 ± 1 mmol/l vs. healthy elderly: 139 ± 1 mmol/l, p=0.03), serum osmolarity (HIV: 276 ± 4 mOsm/l vs. elderly: 288 ± 3 mOsm/l, p=0.03) and free water clearance (HIV: 3.5 ± 3 ml/min/1.73 m² vs. elderly: 5 ± 8 ml/min/1.73 m², p ≤ 0.01). Besides, HIV patients showed an inadequate and significant increase in their urinary tonicity in comparison with the healthy elderly group: HIV: 170 ± 18 mOsm/l vs. elderly: 90 ± 10, p ≤ 0.01. Regarding proximal tubular function, it was found that it was preserved in both groups. Conclusion: Proximal tubule sodium reabsorption was normal, while free water clearance was significantly reduced in young HIV patients in comparison with healthy elderly volunteers.

The HUGE formula (hematocrit, urea, gender) for screening for chronic kidney disease in elderly patients: a study of diagnostic accuracy

Chronically reduced glomerular filtration rate (GFR) in old people does not always mean that they suffer from chronic kidney disease (CKD) since their GFR can just be reduced by aging. The HUGE equation has been recently described and validated in Spain for screening CKD without taking into account the patient’s GFR value. This equation is based on patient’s hematocrit, plasma urea levels and gender. The present study documented that the HUGE equation had and acceptable performance for screening CKD in elderly Argentine patients.

Creatinine clearance with cimetidine in the elderly: response to Dr. Chia-Ter Chao

We thank Dr. Chia-Ter Chao for his comments about our paper. In responding, we will take the opportunity to correct a mistake. Unfortunately, in the paper, we reported the wrong dose of cimetidine: Instead of 800 mg OD (once per day), it should have been written 800 mg BID (twice a day), a dose most recommended in the literature for achieving a complete creatinine secretion inhibition (we referenced these articles in our original paper). We thank Dr. Chao for pointing out this error and giving us the opportunity to correct it [1–3]. Regarding Dr. Chao0s comment on the accuracy of the method used for evaluating the renal reserve, we would like to emphasize that to evaluate this physiological variable we obtained the DELTA value between a peak GFR value and a basal one; thus, obtained DELTA value will be an accurate representation of the magnitude of GFR increase, independently of the accuracy of the applied method for measuring it. Regarding Dr. Chao0s concern about the accuracy of urine volume measurement, we would like to clarify that all the volunteers had a normal bladder voiding (presence of urine retention was one of the exclusion criteria evaluated before the study), and additionally, their urine residual volume was checked by bladder ultrasound after each micturition (this is mandatory when a timed clearance is evaluated). We agree with Dr. Chao that more research is needed in order to know how the aged kidney handles not only creatinine but also cimetidine.