Estimación de la función renal para la dosificación de drogas / Estimation of kidney function to adjust drug dosing

Drug dosing according to renal function is a globally accepted practice whose main purpose is to avoid drug associated toxicity when renal clearance is decreased. Renal function is usually estimated based on creatinine clearance or an estimated glomerular filtration rate (GFR) obtained from one of the available equations based on serum biomarkers. In this review we will analyze the different available methods to adjust the dose of drugs based on GFR, with emphasis on their comparative performance for this objective. Based on this, we will provide some recommendations for drug dosing in chronic and acute renal dysfunction.

Desempeño comparativo de ecuaciones de estimación de excreción urinaria de creatinina

Background: 24-hour urine collection accuracy is generally evaluated based on the values of urine creatinine (UCr) excretion, usually using ranges adjusted by weight. UCr excretion depends on several factors. Equations to estimate UCr in 24-hour collection (UCr/24h) that consider these factors have been developed. However, these formulas have not been evaluated in a sample of Latinamerican origin. Aim: To evaluate the performance of the existing UCr/24 h estimation equations in a sample of Latinamerican origin. Material and Methods: 24-hour urine collections from 181 ambulatory patients were analyzed. Measured UCr/24h was compared with estimated UCr (eUCr) through the equations of Ix (CKD-EPI), Gerber-Mann, Goldwasser, Cockcroft-Gault, Rule, Walser, Kawasaki, Tanaka and Huidobro. Performance of the nine equations to estimate UCr/24h was evaluated with the Pearson correlation and Lin concordance coefficients, and Bland-Altman method. Bias, precision, and accuracy (percentage of collections within 30% of measured UCr or P30) were also calculated. Results: Measured UCr/24h in the 181 patients was 1236 + 378 mg. Correlation coefficient (Pearson) of the eUCr/24h with the equations of Walser, Ix and Huidobro and the measured UCr/24h was strongly positive. Rule and Kawasaki equations had the lowest positive correlation coefficients. Bias was similar using the formulas of Walser, Goldwasser, Kawasaki, Ix and Huidobro. Walser, Ix, Huidobro, Cockcroft-Gault and Goldwasser equations had good accuracy (P30 > 85%), while Gerber-Mann, Tanaka, Rule and Kawasaki formulas had a P30 < 65%. Conclusions: Walser, Ix and Huidobro equations had the best performance to estimate UCr/24h excretion in a population of latinamerican origin.

Evaluación de la función renal en adultos mayores / Evaluation of kidney function in older adults

The evaluation of renal function in older adults is usually carried out with a creatinine clearance or an estimation of glomerular filtration rate using formulas such as Cockcroft-Gault, MDRD or CKD-EPI. The results obtained with these formulas are often regarded as equivalent. However, in adults older than 70 years, the Cockcroft-Gault formula frequently underestimates the glomerular filtration rate with respect to reference methods and the MDRD formula overestimates it. CKD-EPI has a more unpredictable behavior. This leads to erroneously classifying patients in the stages of chronic kidney disease (CKD), artificially increasing the prevalence of this condition, overloading health systems and generating emotional disorders in patients mistakenly classified as carriers of CKD. Also, when kidney function is overestimated, CKD patients are prevented from receiving the treatments appropriate for their condition. In recent years, new formulas have been proposed (FAS, BIS) with a greater accuracy to estimate glomerular filtration rate in older adults. This review describes the behavior of these formulas in a significant number of older adults, from various countries, and proposes using those equations with the best performance in older adults.

Nueva ecuación para la estimación de la natriuresis diaria a partir de parámetros en plasma y orina aislada en población chilena / A new equation to estimate daily natriuresis from parameters in plasma and spot urine sample in the Chilean population

Background: Excessive sodium intake is associated with increased cardiovascular morbidity and mortality. Daily sodium intake is usually inferred from sodium excretion in a 24-hour urine collection, which is cumbersome and prone to errors. Different formulas have attempted to estimate 24-hour urinary sodium from a spot urine sample. Unfortunately, their concordances are insufficient and have not been tested in our population. Aim: To develop an equation to predict 24-hour urine sodium from parameters in plasma and spot urine samples. To validate the equation and compare it with other formulas in Chilean population. Material and Methods: Analysis of 24-hour urine collections, plasma sample and spot urine sample from 174 adult outpatients (81% females) with an estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73m2. These were collected between 2015 and 2019 using standardized methods and educating patients about the correct method to collect 24 h urine samples. In all these patients, creatinine and electrolytes were measured in plasma and urine. A new equation was developed using a multiple linear regression model. Results: Twenty-four-hour urine sodium excretion was significantly correlated with age, weight, height, eGFR, plasma osmolarity, urine electrolytes and parameters obtained from spot urine sample, among others. The new equation had a linear correlation with 24-hour natriuresis of 0.91 and the concordance was 0.9. The predictive capacity of the new equation was better than the existing formulas. Conclusions: We developed a formula to accurately predict daily natriuresis in the Chilean population.

Evaluación de la recolección de orina de 24 horas a partir de la creatininuria: fórmulas para estimarla y su rendimiento / Performance of formulas for the evaluation of 24-hour urine collections using urine creatinine excretion

Creatinine excretion is widely used as a method to evaluate the adequacy of urine collection in different clinical settings. Many factors influence its elimination, such as protein intake, exercise, muscle mass, age, and sex, among many others. As 24-hour urine collections can be cumbersome, several equations have been developed to aid clinicians to correctly interpret results derived from them. In this review article, we report the factors that can modify creatinine excretion and we evaluate the accuracy of different published equations to estimate 24-hour urine creatinine excretion.

¿Son equivalentes los diferentes métodos para estimar la función renal en los adultos mayores? / Comparison of different methods to estimate glomerular filtration rate in older adults

Background: Glomerular filtration rate (GFR) estimation in older adults using a creatinine clearance/24-hour (CrCl) or an equation based on serum creatinine, are often considered equivalent by clinicians. Aim: To compare GFR estimated (eGFR) with the available equations and measured CrCl in patients ≥ 70 years. A secondary aim was to know the differences in chronic kidney disease (CKD) classification, when using the different eGFR formulas. Patients and Methods: In 144 patients aged 77 ± 5 years (58% men), CrCl was measured and GFR was estimated using MDRD, CKD-EPI, BIS-1 and FAS formulas. The eGFR and the stage of CKD were compared according to the different equations used. Results: GFR estimated by MDRD and CKD-EPI equations was 7.8 and 8.4 mL/min/1.73 m2 lower than 24-hour ClCr, respectively. This difference was even greater using the BIS-1 and FAS equations. Twenty-four-hour CrCl classified 47.2% of the patients in a category of renal function > 60 mL/min/1.73 m2, while MDRD and CKD-EPI equations classified just over a third, and BIS-1 and FAS formulas around 20% of the patients. Conclusions: The practice of considering equivalent the GFR estimation using the creatinine-based equations with measured creatinine clearance in older adults should be reconsidered, because their results differ markedly.

Uso de la cistatina C como biomarcador para estimar la tasa de filtración glomerular / Use of cystatin C to estimate glomerular filtration rate

Glomerular filtration rate (GFR) is routinely estimated using endogenous biomarkers due to the complexity of direct measurement methods. Cystatin C is a protease inhibitor produced in all nucleated cells. It is freely filtered and then catabolized by renal tubular cells. Therefore, plasma concentration of cystatin C depends primarily on GFR. Serum cystatin C is less affected by muscle mass, diet, race, gender and age than creatinine. In the general population, equations to estimate GFR based on cystatin C do not have a better performance than those based on creatinine. However, formulas that combine creatinine and cystatin C are more accurate and precise. Estimation of GFR based on cystatin C could be useful in populations in which creatinine value may be biased, such as people with extremely low or high muscle mass, cirrhosis and chronic cardiorenal syndrome. Due to its higher cost in comparison to creatinine, we recommend measuring cystatin C on these clinical situations and when a more accurate estimation of GFR is required.

Reserva funcional renal: concepto y aplicabilidad potencial en la práctica clínica / Renal functional reserve: concept and potential application in clinical practice

Renal functional reserve (RFR) is the capacity of the kidney to increase its glomerular filtration rate (GFR) in response to physiological or pathological stimuli. The most commonly used stimuli to assess this reserve are an oral load of proteins of animal origin, amino acid infusions, dopamine, glucagon or combinations of them. RFR is calculated as the difference between stimulated and baseline GFR. Vegetarians have lower baseline GFR than the general population and an increased RFR. Subjects with only one kidney and those suffering from chronic nephropathies usually have a reduced or absent RFR despite having normal basal GFR. Quantification of RFR may be useful to detect subclinical renal damage, physiological conditions that reduce baseline GFR, evaluation of potential donors for kidney transplantation, suspected hyperfiltration, detection of renal lability against acute injuries or pregnancy and the evaluation after an acute renal injury when renal function seems to be recovered and residual subclinical damage is suspected.

Efectos en la función renal de la suplementación de creatina con fines deportivos / Effects of creatine supplementation on renal function

Creatine supplements may transitorily rise serum creatinine levels and mimic a kidney disease. If its use is associated with a high protein diet, the resulting increase in blood urea nitrogen will increase the confusion. Since clinical laboratories usually inform the estimated glomerular filtration rate based on serum creatinine, its elevation may lead to over diagnose a chronic renal failure, with the inherent personal and public health consequences. Creatine supplements are safe and do not cause renal disease. Reports of kidney damage associated with its use are scanty. However, creatine supplements should not be used in people with chronic renal disease or using potentially nephrotoxic medications.

Recurrencia de Síndrome de Goodpasture con negativización de anticuerpos anti-membrana basal glomerular: caso clínico / Recurrence of goodpasture syndrome with negative antiglomerular basement antibodies: report of one case

Goodpasture Syndrome is described as a single episode disease entity. It is diagnosed with the demonstration of antiglomerular basement (anti-GBM) antibodies in plasma or renal tissue. Although the recurrence of anti-GBM disease is rare, it has been reported in up to 3% of cases. Recurrence with negative anti-GBM antibodies in plasma is even less frequent We report a 63 years old male in whom anti-GBM disease recurred without detectable anti-GBM antibodies in plasma, despite having positive antibodies at the onset.

Hipercalcemia severa en el curso de rabdomiolisis: caso clínico / Rhabdomyolysis and severe hypercalcemia: report of one case

Rhabdomyolysis (RD) is the process that leads to cell destruction of striated muscle. Causes include inherited metabolic defects or acquired disorders. RD is frequently associated with acute kidney injury (AKI) and disorders of calcium metabolism. We report a 33 year old man that after amphetamine consumption and an uninterrupted 3,000 km driving presented vomiting, muscle pain and dark urine. He had elevated creatinkinase levels, severe hypocalcemia and an acute renal failure. He was treated with hemodialysis and calcitriol. He was transferred to our hospital and on admission a serum calcium of 18 mg/dl was detected. He continued on hemodialysis, recovering renal function and with normalization of creatinkinase levels and serum calcium level.

Creatinina y su uso para la estimación de la velocidad de filtración glomerular / Estimation of glomerular filtration rate with creatinine

Glomerular filtration rate (GFR) is the best approximation to global renal function and its estimation is of great relevance for clinical practice. Since the measurement of GFR by reference methods is complex, costly and not widely available, its routine evaluation is performed using endogenous biomarkers. Within these, creatinine is the most commonly used. It allows the estimation of GFR by means of its clearance or by formulas based on its concentration on plasma. Creatinine measurement should be performed using enzimatic methods as they confer more accurate values than Jaffe methods, especially for normal and low creatinine levels.

Función renal al fallecimiento según causa de muerte en trasplantados renales / Glomerular filtration rate before death, in patients who died with a functioning kidney graft

Background: Death with a functioning kidney graft is now the leading cause of graft loss after renal transplantation. Aim: To determine if renal function at the last outpatient visit before the recipient’s death was different according to the following causes of death: infections, cardiovascular diseases, gastrointestinal disorders or cancer. Patients and Methods: Retrospective cooperative cohort study conducted in two kidney transplant centers. All patients who received a kidney graft in the last 32 years were included. During that lapse, 431 kidney transplants were performed. Among them, 85 patients died with a functioning graft and were classified due to their cause of death. Glomerular filtration rate (eGFR) was estimated with the Modification of Diet in Renal Disease formula. Declining renal function was defined as a > 20% decline in eGFR during the last 6 months prior to the last outpatient visit. Results: Eighty four patients were included in the analysis. Of these, 28.2% died of cardiovascular causes, 35.3% of infectious diseases, 15.3% of cancer and 20% of digestive diseases. Patients dying from cancer had a significantly higher eGFR prior to death than those who died from cardiovascular causes, infectious and digestive diseases (p < 0.01). Declining renal function occurred in 34.8% of deaths from cardiovascular causes, 39.3% from infectious diseases, 16.7% from cancer and 40% from digestive diseases. There were no significant differences between groups. Conclusions: Kidney graft recipients who die with a functioning graft have better renal function prior to their death when it is due to cancer than when it originates from infectious, cardiovascular or digestive diseases. Declining renal function is similar in the four groups of death causes.

Influencia de la ganancia de peso durante el primer año del trasplante renal en la sobrevida de injertos y pacientes / Influence of weight gain during the first year after kidney transplantation in the survival of grafts and patients

Background: After receiving a kidney allograft, patients tend to gain weight acquiring the risk associated with overweight and obesity. Aim: To compare the evolution during 10 years after transplantation of patients who gained more than 15% of their initial weight during the first year after receiving the graft with those who did not experience this increase. Material and Methods: Cohort study of 182 patients transplanted in a single hospital between 1981 and 2003. Demographic data, weight gain during the first year, drugs used, complications and evolution of patients and grafts were recorded. Results: Seventy two patients gained more than 15% of their weight during the first year. These were discharged after receiving the graft with a lower serum creatinine than their counterparts (1.46 ± 0.71 and 1.97 ± 1.74 mg/dl respectively, p = 0.02). Ten years mortality with a functioning kidney was higher among weight gainers (25 and 12.7% respectively, p = 0.03). No other differences were observed between groups. Conclusions: Patients who gained more than 15% of their initial weight during the first year after receiving a kidney graft have a higher 10 years mortality with a functioning kidney.

Resultados a 10 años en trasplantes renales con donantes vivos no relacionados: Experiencia de 22 años / Survival among renal allograft recipients from non related living donors

Background: There is a gap between the number of patients requiring a renal allograft and the number of potential deceased donors (DD). One alternative is using allografts from non-related living donors (NRLD). Aim: To compare survival and complications of renal allograft recipients from DD, related living donors (RLD) and NRLD. Material and Methods: Observational study of a cohort of renal allograft recipients. Of 253 transplants performed in a Chilean region between 1981 and 2003, 20 patients received and allograft from a NRLD. Graft and patient survival of these patients were compared with those of 93 patients receiving an allograft from a related living donor and 140 receiving it from a DD. Patients were followed for 10 years or until death or dialysis requirement. Results: No significant differences between groups in graft and patient survival, deaths with a functioning graft or return to dialysis were observed. Receptors of DD had more hospital admissions during the first years after receiving the graft, usually due to infections. Also a delayed graft function was more common among them. Glomerular filtration rate ten years after the graft was similar among the three groups. Conclusions: No differences in graft or patient survival was observed between patients receiving a renal allograft from NRLD, RLD or DD.