Compensatory gomerular filtration rate (GFR) increase after kidney donation results in a GFR above 50% of the predonation value. The renal functional reserve (RFR) assessed by the renal response to dopamine infusion (RFR_dopa) is considered to reflect functional reserve capacity and is thought to be a tool for living donor screening. However, it is unknown if the RFR_dopapredicts long-term kidney function. Between 1984 and 2017, we prospectively measured GFR (¹²⁵I-iothalamate) and RFR by dopamine infusion in 937 living kidney donors. We performed linear regression analysis of predonation RFR_dopaand postdonation GFR. In donors with 5-yr follow-up after donation we assessed the association with long-term GFR. Mean donor age was 52 yr (SD 11); 52% were female. Mean predonation GFR was 114 ml/min (SD 22), GFR_dopawas 124 ml/min (SD 24), resulting in an RFR of 9 ml/min (SD 10). Three months postdonation, GFR was 72 ml/min (SD 15) and GFR_dopawas 75 ml/min (SD 15), indicating that donors still had RFR_dopa[3 ml/min (SD 6), P < 0.001]. Predonation RFR_dopawas not associated with predonation GFR [standardized (st.) β −0.009, P = 0.77] but was positively associated with GFR 3 mo after donation (st. β 0.12, P < 0.001). In the subgroup of donors with 5-yr follow-up data ( n = 383), RFR_dopawas not associated with GFR at 5 yr postdonation (st. β 0.05, P = 0.35). In conclusion, RFR_dopais a predictor of short-term GFR after living kidney donation but not of long-term kidney function. Therefore, measurement of the RFR_dopais not a useful tool for donor screening. Studies investigating long-term renal adaptation are warranted to study the effects of living kidney donation and improve donor screening.

Background: Several studies have found a U-shaped association between sodium intake and mortality. The increased mortality risk of low sodium intake has raised debates and hampers widespread acceptance of public health campaigns and dietary guidelines on reducing sodium intake. Whether the excess risk can be attributed to low sodium intake alone or concomitant inadequate intake of other relevant nutrients is unknown. Objective: We investigated whether concomitant low protein intake could explain the lower part of the U-shaped association of sodium intake with all-cause mortality. Methods: We included 1603 individuals aged between 60 and 75 years old from the gender- and socioeconomic status-balanced prospective Lifelines-MINUTHE cohort study. Using multivariable Cox regression analyses, we investigated the association of sodium intake (24 h urinary sodium excretion) with all-cause mortality, including the interaction with protein intake calculated from the Maroni formula. Results: Mean intakes of sodium and protein were 3.9 ± 1.6 g/day and 1.1 ± 0.3 g/kg/day, respectively. After a median follow-up of 8.9 years, 125 individuals (7.8%) had died. The proportion of participants with insufficient protein intake (<0.8 g/kg/day) was inversely related to sodium intake (i.e., 23.3% in Q1 versus 2.8% in Q4, p < 0.001). We found an increased risk for mortality in both the highest quartile (Q4, >4.7 g/day; hazard ratio (HR) 1.74 (95% confidence interval (CI) 1.03–2.95)) and the lowest two quartiles of sodium intake (Q1, 0.7–2.8 g/day; 2.05 (1.16–3.62); p = 0.01 and Q2, 2.8–3.6 g/day; 1.85 (1.08–3.20); p = 0.03), compared with the third quartile of sodium intake (Q3, 3.6–4.7 g/day). This U-shaped association was significantly modified by protein intake (P_interaction = 0.006), with the increased mortality risk of low sodium intake being reversed to the lowest mortality risk with concomitant high protein intake. In contrast, the increased mortality risk of low sodium intake was magnified by concomitant low protein intake. Conclusions: We found that a higher protein intake counteracts the increased mortality risk observed in subjects with a low sodium intake. In contrast, a joint low intake of sodium and protein is associated with an increased mortality risk, allegedly due to poor nutritional status. These findings support the guidelines that advocate a lower sodium intake, while highlighting the importance of recognizing overall nutritional status among older adults.

In the general population we recently reported a consistent association between plasma sodium and volume markers, suggesting that individuals with higher plasma sodium have higher extracellular fluid volume (ECFV). To test this hypothesis, we analyzed the association between plasma sodium and directly measured ECFV (iothalamate distribution volume) in healthy men. Second, we studied whether plasma sodium is associated with blood pressure. We analyzed data from 70 men (age 24 ± 7 years) at the end of two 7-day periods on a low-sodium diet (LS, 50 mmol Na/24 h) and a high-sodium diet (HS, 200 mmol Na/24 h), respectively. The association of plasma sodium with blood pressure was assessed in the combined data of the different sodium intakes by linear mixed effects models. A positive univariable association between plasma sodium and ECFV was found during HS (β = 0.24, p = 0.042) and LS (β = 0.23, p = 0.058), respectively. Individual values of plasma sodium on LS and HS diet were strongly correlated (β = 0.68, p < 0.001), as were values for ECFV (β = 0.54, p < 0.001). In the combined data set plasma sodium level was significantly associated with ECFV (B [SE] = 0.10 [0.04], p = 0.02), and systolic blood pressure (SBP, B [SE] = 0.73 [0.26], p = 0.006), independent of ECFV. In conclusion, plasma sodium concentration is positively associated with ECFV on both LS and HS intake. Our data confirm and extend prior data on individual regulation of plasma sodium and suggest that this is associated with individuality of the regulation of ECFV. Finally, plasma sodium level is associated with SBP, independent of ECFV and diet.

Plasma Na⁺concentration is regulated within narrow limits. Yet, substantial interindividual differences exist even in the normal range. The determinants of these differences are not well understood. We therefore investigated the clinical and neurohumoral associates of plasma Na⁺. We studied 2,364 men (age: 48 ± 12 yr) and 2,710 women (age: 47 ± 12 yr) from the prospective Prevention of Renal and Vascular End-Stage Disease (PREVEND) cohort study. In the present study, we investigated the neurohumoral factors NH₂-terminal prohormone of brain natriuretic peptide (NT-proBNP) and aldosterone as volume markers and copeptin as a marker for osmoregulation. Clinical associating variables of plasma Na⁺were age, sex, and plasma glucose. Furthermore, plasma Na⁺levels were associated with log₂copeptin (men: standardized β = 0.18, P < 0.001; women: standardized β = 0.17, P < 0.001), log₂NT-proBNP (men: standardized β = 0.07, P = 0.008; women: standardized β = 0.12, P < 0.001), and log₂aldosterone (men: standardized β = −0.06, P = 0.005; women: standardized β = −0.09, P < 0.001). Copeptin and NT-proBNP showed an interaction in their association with plasma Na⁺. Thus, our data 1) support that osmoregulation, as estimated from copeptin levels, is a main associate of plasma Na⁺; 2) show a consistent association with volume markers, with higher NT-proBNP and lower aldosterone in individuals with higher plasma Na⁺; and 3) show that the interaction between copeptin and NT-proBNP illustrates that osmoregulation and volume regulation act in concert in the regulation of plasma Na⁺.