Functional Adaptation After Kidney Tissue Removal in Patients Is Associated With Increased Plasma Atrial Natriuretic Peptide Concentration

Nessn Azawi; Mia Jensen; Boye L. Jensen; Jens P. Gtze; Claus Bistrup; Lars Lund

Disclosures

Nephrol Dial Transplant. 2022;37(11):2138-2149. 

In This Article

Abstract and Introduction

Abstract

Graphical Abstract

Background: Following nephrectomy, the remaining kidney tissue adapts by an increase in glomerular filtration rate (GFR). In rats, hyperfiltration can be transferred by plasma. We examined whether natriuretic peptides, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) increase in plasma proportionally with kidney mass reduction and, if so, whether the increase relates to an increase in GFR.

Methods: Patients (n = 54) undergoing partial or total unilateral nephrectomy at two Danish centres were followed for 1 year in an observational study. Glomerular filtration rate was measured before, and 3 and 12 months after surgery. Natriuretic propeptides (proANP and proBNP) and aldosterone were measured in plasma before and at 24 h, 5 days, 21 days, 3 months and 12 months. Cyclic guanosine monophosphate (cGMP) was determined in urine.

Results: There was no baseline difference in GFR between total and partial nephrectomy (90.1 mL/min/1.73 m2 ± 14.6 versus 82.9 ± 18; P = 0.16). Single-kidney GFR increased after 3 and 12 months (12.0 and 11.9 mL/min/1.73 m2, +23.3%). There was no change in measured GFR 3 and 12 months after partial nephrectomy. ProANP and proBNP increased 3-fold 24 h after surgery and returned to baseline after 5 days. The magnitude of acute proANP and proBNP increases did not relate to kidney mass removed. ProANP, not proBNP, increased 12 months after nephrectomy. Plasma aldosterone and urine cGMP did not change. Urine albumin/creatinine ratio increased transiently after partial nephrectomy. Blood pressure was similar between the groups.

Conclusion: ANP and BNP increase acutely in plasma with no relation to degree of kidney tissue ablation. After 1 year, only unilateral nephrectomy patients displayed increased plasma ANP, which could support adaptation.

Introduction

The increase in the glomerular filtration rate (GFR) between resting state and maximum capacity is known as the renal functional reserve.[1] Living donor nephrectomy is associated with an increase in the single kidney and thus single nephron GFR (snGFR) after surgery reflecting the higher functional demand.[2,3] The increase is acute and persistent.[4] While this was attributed previously to increases in renal blood flow, magnetic resonance imaging studies contest this view by showing that GFR increases in association with a relatively minor change or even a decrease in total kidney perfusion and cortical perfusion after nephrectomy.[5] Consistent data show that an increase in GFR is relatively more extensive than in renal plasma flow (RPF), suggesting differential and balanced effects on glomerular arterioles with preferential efferent resistance increase and/or afferent resistance decrease.[5,6] Pioneering studies showed that infusion of plasma from rats nephrectomized before plasma harvest conferred an increase in snGFR, tubular fluid flow rate and sodium excretion upon transfusion into recipient rats,[7] suggesting that circulating factors were responsible. Angiotensin II (ANGII) and aldosterone concentrations increased in plasma harvested from nephrectomized rats.[7] These sodium-retaining hormones are less likely as mediators of increased sodium excretion. The cardiac natriuretic peptides appear relevant. Natriuretic peptides, best documented for atrial natriuretic peptide (ANP), exert differential effects on glomerular arterioles, at least in rodents, with afferent relaxation and efferent constriction.[8–12] In patients with acute kidney failure, ANP infusion increases renal blood flow, filtration fraction and GFR.[13,14] However, ANP concentration was not increased in plasma from uninephrectomized rats.[7] Brain natriuretic peptide (BNP) was not determined. BNP infusion to healthy humans at a slightly supraphysiological level increases urinary flow rate, sodium excretion and GFR, while RPF decreases.[15] Chronic kidney disease is associated with elevated plasma concentration of natriuretic peptides, best described for the more stable prohormone proBNP (often referred to as NT-proBNP).[13,16] Because of high renal extraction of natriuretic peptides and their molecular precursors,[17] it seems likely that an abrupt decrease in GFR by removal of kidney tissue increases natriuretic peptide concentrations proportional to the loss of nephron mass and that such an acute increase could initiate and maintain the adaptive renal functional increase. Data show that natriuretic peptide receptors in podocytes confer protection of the filtration barrier.[18] There is now a possibility to test a relation between tissue removal and natriuretic peptides directly in human patients. Total unilateral nephrectomy is replaced progressively by 'nephron-sparing' surgical techniques, denoted partial nephrectomy, which has become the golden standard for treating small tumour masses. The present study was designed to characterize longitudinal changes in ANP and BNP plasma concentration in patients undergoing partial and total unilateral nephrectomy. The aim was to associate acute changes in natriuretic peptides to the degree of kidney mass reduction and to renal functional adaptation, blood pressure and kidney injury. Specifically, it was hypothesized that (i) magnitude of kidney mass reduction relates directly to plasma increase in natriuretic peptide concentrations, with larger sensitivity in proBNP than proANP, and (ii) such an increase relates directly to compensatory functional increase and inversely to kidney injury and blood pressure.

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