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. 2018 Dec;596(24):6191-6203.
doi: 10.1113/JP276973. Epub 2018 Oct 28.

Renal reactivity: acid-base compensation during incremental ascent to high altitude

Shaelynn M Zouboules  1 , Hailey C Lafave  1 , Ken D O'Halloran  2 , Tom D Brutsaert  3 , Heidi E Nysten  4 , Cassandra E Nysten  1 , Craig D Steinback  5 , Mingma T Sherpa  6 , Trevor A Day  1
Affiliations

Renal reactivity: acid-base compensation during incremental ascent to high altitude

Shaelynn M Zouboules et al. J Physiol. 2018 Dec.

Abstract

Key points: Ascent to high altitude imposes an acid-base challenge in which renal compensation is integral for maintaining pH homeostasis, facilitating acclimatization and helping prevent mountain sicknesses. The time-course and extent of plasticity of this important renal response during incremental ascent to altitude is unclear. We created a novel index that accurately quantifies renal acid-base compensation, which may have laboratory, fieldwork and clinical applications. Using this index, we found that renal compensation increased and plateaued after 5 days of incremental altitude exposure, suggesting plasticity in renal acid-base compensation mechanisms. The time-course and extent of plasticity in renal responsiveness may predict severity of altitude illness or acclimatization at higher or more prolonged stays at altitude.

Abstract: Ascent to high altitude, and the associated hypoxic ventilatory response, imposes an acid-base challenge, namely chronic hypocapnia and respiratory alkalosis. The kidneys impart a relative compensatory metabolic acidosis through the elimination of bicarbonate (HCO3- ) in urine. The time-course and extent of plasticity of the renal response during incremental ascent is unclear. We developed an index of renal reactivity (RR), indexing the relative change in arterial bicarbonate concentration ([HCO3- ]a ) (i.e. renal response) against the relative change in arterial pressure of CO2 ( PaCO2 ) (i.e. renal stimulus) during incremental ascent to altitude ( Δ[HCO3-]a/ΔPaCO2 ). We aimed to assess whether: (i) RR magnitude was inversely correlated with relative changes in arterial pH (ΔpHa ) with ascent and (ii) RR increased over time and altitude exposure (i.e. plasticity). During ascent to 5160 m over 10 days in the Nepal Himalaya, arterial blood was drawn from the radial artery for measurement of blood gas/acid-base variables in lowlanders at 1045/1400 m and after 1 night of sleep at 3440 m (day 3), 3820 m (day 5), 4240 m (day 7) and 5160 m (day 10) during ascent. At 3820 m and higher, RR significantly increased and plateaued compared to 3440 m (P < 0.04), suggesting plasticity in renal acid-base compensations. At all altitudes, we observed a strong negative correlation (r ≤ -0.71; P < 0.001) between RR and ΔpHa from baseline. Renal compensation plateaued after 5 days of altitude exposure, despite subsequent exposure to higher altitudes. The time-course, extent of plasticity and plateau in renal responsiveness may predict severity of altitude illness or acclimatization at higher or more prolonged stays at altitude.

Keywords: Acid-Base Physiology; High Altitude; Metabolic Acidosis; Renal Compensation; Respiratory Alkalosis.

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Figures

Figure 1
Figure 1. Ascent profile of expedition in the Everest region in Nepal
Arrows indicate data collection points and locations. *Baseline data were either collected at 1400 m (as shown) or ∼1 week earlier, prior to departure, at 1045 m.
Figure 2
Figure 2. Changes in arterial blood variables with ascent to high altitude
A, partial pressure of arterial O2 (PaO2; mmHg). B, partial pressure of arterial CO2 (P aC O2; mmHg). C, concentration of arterial bicarbonate ([HCO3 −]a; mmol L–1). D, arterial pH (pHa). Note that baseline data (1045 and 1400 m) were pooled. A black circle indicates mean values. *Statistically significant difference from baseline (1045 /1400 m) (P < 0.05). †Statistically significant difference from prior altitude (P < 0.05).
Figure 3
Figure 3. The relationship between ΔpHa and RR with ascent to high altitude
A, RR (Δ[HCO3 −]a)/ΔP aC O2). B, ΔpHa. A black circle indicates mean values. Delta values at each altitude are compared to baseline values (see Eqn (2)). *Statistically significant difference from 3440 m (P < 0.05). Days reported represent days of altitude exposure.
Figure 4
Figure 4. Correlations between ΔpHa and RR (Δ[HCO3 −]a)/ΔP aCO 2) with ascent to high altitude
A, 3440 m, day 3. B, 3820 m, day 5. C, 4240 m, day 7. D, 5160 m, day 10. Correlation coefficients (r), P values, slope of the linear response and n are reported in each case. Delta values at each altitude are compared to baseline values (see Eqn (2)). Days reported represent days of altitude exposure.
Figure 5
Figure 5. Davenport acid‐base diagrams during incremental ascent to high altitude
Demonstration of the Henderson‐Hasselbalch relationship depicting acid‐base disturbances and their corresponding compensations, including arterial blood pHa (x‐axis), [HCO3 − a] (y‐axis), P aC O2 isopleths and the [non‐HCO3 − buffer] slope. Solid grey lines represent partial pressure of P aC O2 isopleths. The dashed grey line represents the standard non‐HCO3 − buffer slope. A, template Davenport diagram illustrating the CO2 isopleths and the position of the reference baseline value, where arterial HCO3 − is 24 mmol L–1 (y‐axis), arterial pH (pHa) is 7.4 (x‐axis) and partial pressure of arterial (Pa)CO2 is 40 mmHg. B, 1045/1400 m low altitude baseline for comparison (n = 20). C, 3440 m on day 3 of ascent (n = 18). D, 3820 m on day 5 of ascent (n = 17). E, 4240 m on day 7 of ascent (n = 15). F, 5160 m on day 10 of ascent (n = 13). Days reported represent days of altitude exposure.
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