Supramaximal elevation in B-type natriuretic peptide and its N-terminal fragment levels in anephric patients with heart failure: a case series

Abstract Introduction Little is known about the responses of natriuretic peptides to developing congestive heart failure in ‘anephric’ end-stage kidney disease. Case presentation We present three consecutive cases of surgically-induced anephric patients in a critical care environment: a 28-year-old Caucasian woman (with congestive heart failure), a 42-year-old Caucasian woman (without congestive heart failure), and a 23-year-old Caucasian woman (without congestive heart failure). Our limited study data indicate that cut-off values advocated for B-type natriuretic peptide and its N-terminal fragment to ‘rule out’ congestive heart failure in two of our end-stage kidney disease patients (without congestive heart failure) are largely appropriate for anephric patients. However, our index (first) patient developed congestive heart failure accompanied by the phenomenon of massive and persistent elevation of these natriuretic levels. Conclusion Our findings suggest that patients from the anephric subclass suffering from congestive heart failure will develop supramaximal elevation of B-type natriuretic peptide and its N-terminal fragment, implying the need for dramatically higher cut-off values with respective magnitudes of the order of 50-fold (B-type natriuretic peptide ~5780pmol/L; 20,000ng/L) to 100-fold (N-terminal fragment ~11,800pmol/L; 100,000ng/L) higher than current values used to ‘rule in’ congestive heart failure. Further research will be required to delineate those cut-off values. The role of our devised ‘Blood Volume – B-type natriuretic peptide feedback control system’ on ‘anatomical’ and ‘functional’ anephric patients led to significant mathematically-enriched arguments supporting our proposal that this model provides plausible explanations for the study findings, and the model lends support to the important hypothesis that these two groups of anephric patients inflicted with congestive heart failure should effectively have similar natriuretic response behavior.</p

Listing of Countries Utilizing DCD and Relevant Maastricht Categories (Adapted from Dominguez-Gil B, Haase-Kromwijk B, Van Leiden H, Neuberger J, Coene L, et al.) [18].

<p>In addition to the countries listed above, the following countries have reported occasional, very low rates of DCD donation activity since 2000: Algeria, Bolivia, Brazil, Croatia, Hong Kong SARC, Lebanon, Pakistan, Romania, Saudi Arabia, Singapore, South Korea, Turkey and Ukraine.</p

Donation after Brain Death (DBD) rates vs (a) Donation after Cardiocirculatory Death (DCD) rate (b) controlled Donation after Cardiocirculatory Death (cDCD) rate and (c) uncontrolled Donation after Cardiocirculatory Death (uDCD) rate.

<p>Solid lines are the Lowess curve of the predicted values from the fitted model.</p

Average (a) Deceased Donors (DD), (b) Donation after Brain Death (DBD) and (c) Donation after Cardiocirculatory Death (DCD) rates over time by Group One (solid line), Group Two (dashed line) and Group Three (dotted line) countries.

<p>Average (a) Deceased Donors (DD), (b) Donation after Brain Death (DBD) and (c) Donation after Cardiocirculatory Death (DCD) rates over time by Group One (solid line), Group Two (dashed line) and Group Three (dotted line) countries.</p

Transplant Rate by (a) Donation after Brain Death (DBD) rate and (b) Donation after Cardiocirculatory Death (DCD) rate.

<p>Solid lines are the Lowess curve of the predicted values from the fitted model.</p

Boxplots of Average Number of Transplanted Organs per DBD and DCD Donor.

<p>Mean difference for number of transplants by donor type = 1.51 (95% CI: 1.42,1.60, p<0.001).</p

Pre-RRT nerve excitability recordings.

<p>Patients receiving hemodiafiltration (HDF) (empty circles) and standard high-flux HD (black filled circles) compared to 95% limits for healthy controls (dashed lines). (A) Depolarising and hyperpolarising threshold electrotonus curves. (B) Recovery cycle curve of excitability, large empty arrows indicate the direction of change with axonal depolarization. In both figures (A) and (B) the HDF group demonstrate results significantly closer to normal values than the HFHD group, specifically at hyperpolarising threshold electrotonus 90–100 ms (TEh90–100 ms), refractoriness and superexcitability. Figures (C) and (D) demonstrate the group differences in TEh90–100 ms and refractoriness in histogram format. *<i>p<</i>0.05, **<i>p<</i>0.001.</p

Longitudinal follow-up 18 months of patients who remained on their respective treatment (HDF n = 4 and HFHD n = 7).

<p>Panels (A) and (B) demonstrate a relative stability of nerve excitability results in patients who remained on their respective treatments at baseline (white bars) and longitudinal follow-up (black bars). Additionally these graphs depict the sustained significant difference between HDF and HFHD in both hyperpolarising threshold electrotonus 90–100 ms (TEh90–100 ms) and refractoriness. *<i>p<</i>0.05, **<i>p<</i>0.001. Panels (C) and (D) show the results of a single patient switched from HDF to HFHD. Threshold electrotonus (C) and recovery cycle parameters (D) demonstrate the profound abnormalities at longitudinal follow-up on HFHD.</p