Renal creatinine handling in very old patients with chronic renal disease

Musso, Carlos G.; Michelángelo, Hernán; Vilas, Manuel; Martínez, B.; Bonetto, Alberto; Jauregui, Ricardo; Algranati, L

doi:10.1007/s11255-010-9886-5

Cited by 11 publications

(8 citation statements)

References 11 publications

(10 reference statements)

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“…The large betweenpatient variability in FE creat is in line with a prior small study in renal transplant recipients by Schück et al (45), who also noted FE creat Ͻ1, calculated as the ratio of creatinine to polyfructosan clearance, in some patients. Creatinine reabsorption, albeit infrequent, has been described previously (30,31,35,45). It is considered physiological in newborns and the elderly and is attributed to tubular characteristics allowing for "back-leak" of creatinine, namely an immature tubular structure with increased permeability in newborns and tubular atrophy in the elderly, respectively (30,31).…”

Section: Discussionmentioning

confidence: 82%

“…Creatinine reabsorption, albeit infrequent, has been described previously (30,31,35,45). It is considered physiological in newborns and the elderly and is attributed to tubular characteristics allowing for "back-leak" of creatinine, namely an immature tubular structure with increased permeability in newborns and tubular atrophy in the elderly, respectively (30,31). Moreover, it has been reported in pathological conditions, such as decompensated heart failure or uncontrolled diabetes (35).…”

Section: Discussionmentioning

confidence: 82%

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SLC22A2is associated with tubular creatinine secretion and bias of estimated GFR in renal transplantation

Reznichenko

Sinkeler

Snieder

et al. 2013

Physiological Genomics

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-Genomewide association studies reported SLC22A2 variants to be associated with serum creatinine. As SLC22A2 encodes the organic cation transporter 2 (OCT2), the association might be due to an effect on tubular creatinine handling. To test this hypothesis we studied the association of SLC22A2 polymorphisms with phenotypes of net tubular creatinine secretion: fractional creatinine excretion (FE creat) and bias of estimated glomerular filtration rate (eGFR). We also studied the association with end-stage renal disease (ESRD) and graft failure (GF) in renal transplant recipients. SLC22A2 single nucleotide polymorphisms (SNPs), rs3127573 and rs316009, were genotyped in 1,142 ESRD patients receiving renal transplantation and 1,186 kidney donors as controls. GFR was measured with 125 I-iothalamate clearance. Creatinine clearance was also assessed. FEcreat was calculated from the simultaneous clearances of creatinine and 125 I-iothalamate. Donor rs316009 was associated with FEcreat (beta Ϫ0.053, P ϭ 0.024) and with estimated [modification of diet in renal disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)] but not measured GFR. In line with this, donor rs316009 was associated with bias of the MDRD and CKD-EPI but not the Cockroft-Gault equation. Both SNPs were associated with ESRD: odds ratios [95% CI] 1.39 [1.16 -1.67], P ϭ 0.00065, and 1.23 [1.02-1.48], P ϭ 0.042, for rs3127573 and rs316009, respectively. Neither SNP was associated with GF. Thus, SLC22A2 is associated with phenotypes of net tubular creatinine secretion and ESRD. creatinine tubular secretion; SNP; genetic polymorphism; GWAS; OCT2 GENOME-WIDE ASSOCIATION STUDIES (GWAS) identified a number of loci influencing renal function (7, 23, 24) usually using renal function estimates based on serum creatinine as a proxy for glomerular filtration rate (GFR).Serum creatinine, however, is determined not only by GFR, but also by the rate of creatinine generation, extrarenal elimination, and by tubular handling (5,31,35,46,49). Dissecting the biological mechanisms underlying genetic associations with serum creatinine, therefore, is pivotal for proper interpretation of GWAS findings. In particular, it is relevant to assess whether loci associated with serum creatinine reflect susceptibility to renal damage (1) or, alternatively, reflect biological variations in creatinine generation or in creatinine handling unrelated to the risk for renal damage.The SLC22A2 gene is associated with serum creatinine and estimated GFR (eGFR) (7). However, SLC22A2 might well be a creatinine secretion locus. First, SLC22A2 single nucleotide polymorphisms (SNPs) were associated with GFR estimated from serum creatinine but not cystatin C (23, 34). Second, the SLC22A2 gene encodes the organic cation transporter 2 (OCT2), a predominant transporter involved in tubular creatinine secretion. It is expressed in the basolateral membrane of proximal tubule cells (29), where it mediates creatinine uptake from the peritubular capillaries, as an initial step in tubular crea...

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Section: Discussionmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 82%

SLC22A2is associated with tubular creatinine secretion and bias of estimated GFR in renal transplantation

Reznichenko

Sinkeler

Snieder

et al. 2013

Physiological Genomics

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“…However, this decrease does not correspond to serum creatinine levels, making it difficult to assess kidney dysfunction in this group of patients. 9,10 There are several formulas that use blood creatinine together with other factors including age, sex, weight, and height to calculate the GFR. However, validation of these is limited in people older than 70 years, and the prognostic implications of these surrogate markers of kidney function are not well determined.…”

Section: Introductionmentioning

confidence: 99%

Clinical Impact of Indirect Markers of Renal Function in Elderly Patients With Hip Fracture

López-Martínez

Tovar-Rivera

Becerra-Laparra

et al. 2014

Geriatr Orthop Surg Rehabil

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Introduction: There are risk factors associated with mortality in patients older than 70 years with hip fracture, including kidney function. However, indirect formulas to calculate glomerular filtration rate are not validated in patients older than 70 years. We analyzed whether the formula hematocrit, urea, and gender (HUGE) can be used as a prognostic factor. Material and Methods: A retrospective cohort study of 88 patients older than 70 years with a diagnosis of hip fracture. At admission, clinical and biochemical parameters were measured and glomerular filtration rate by Cockcroft-Gault, Modification Of Diet In Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), and HUGE value. Accuracy to assess long-term mortality was analyzed with receiver-operating curve analysis. Cox regression analysis was performed to identify risk factor for mortality. Results: Sample included 88 patients; overall mortality was 13.63%, 17.85%, 28.57%, and 75.85% at 6 months, 1, 2, and 3 years, respectively. There was no significant difference in glomerular filtration rate by different formulas, contrary to HUGE, with higher values in the mortality group (1.83 + 6.38 vs À2.61 + 2.70, P ¼ .0001). Survival was lower in patients with higher HUGE values (22.7 months, 95% confidence interval [CI] 16.1-29.5 vs 32.9 months, 95% CI 30.2-35.7; P .001). In the Cox regression analysis, a negative HUGE value is associated with lower mortality (hazards ratio ¼ 0.238; 95% CI 0.568-0.099). Conclusion: The HUGE formula is an independent risk factor for mortality in elderly patients with hip fracture, but not the glomerular filtration rate determined by Cockcroft-Gault, MDRD, and CKD-EPI.

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“…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][2][3]. Regarding Dr. Chao 0 s 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.…”

Section: Editormentioning

confidence: 99%

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

et al. 2011

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Renal creatinine handling in very old patients with chronic renal disease

Abstract: Creatinine secretion pattern in very old patients with advanced chronic renal disease is similar to that observed in young ones with similar level of CKD.

Cited by 11 publications

References 11 publications

SLC22A2is associated with tubular creatinine secretion and bias of estimated GFR in renal transplantation

SLC22A2is associated with tubular creatinine secretion and bias of estimated GFR in renal transplantation

Clinical Impact of Indirect Markers of Renal Function in Elderly Patients With Hip Fracture

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

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