Increased intrarenal post-glomerular blood flow is a key condition for the development of calcineurin inhibitor-induced renal tubular acidosis in kidney transplant recipients.

Abstract

Hyperchloremic metabolic acidosis (HCMA) from renal tubular acidosis (RTA) is common in kidney transplant (KT) recipients. Calcineurin inhibitors (CNIs) are a potential cause of RTA, and whether HCMA is a determinant of poor graft prognosis is controversial. The subjects were living-donor KT recipients (LDKTRs, n=47) and matched donors (n=43). All cases of rejection, extrarenal causes, and respiratory disorders were excluded. HCMA was defined as having a [Na+]-[Cl- ] value of ≤34 or starting alkalization. We determined the potential causes of HCMA in LDKTRs at 3 months (m) and 1 year (y) post-KT. We examined renal hemodynamic parameters in 26 LDKTRs at 1 y post-KT: namely, glomerular filtration rate (GFR), renal plasma flow (RPF), filtration fraction (FF; GFR/RPF) and pre-/post-glomerular vascular resistance (pre-/postVR). The HCMA incidence in the 3-m post-KT LDKTR group was higher than that of the donors (51.0%vs. 6.9%, p<0.001, adjusted odds ratio: 6.7-15.7). Among adjusted factors, the most dominant HCMA contributor was low hemoglobin concentration (Hb≤12g/dl). Compared to non-HCMA cases, HCMA patients had low FF and low post-VR (p=0.008, 0.003, respectively) suggesting increased intrarenal post-glomerular blood flow. The high pathological score of alternative arteriolar hyalinosis (aah) ≥2 was a significant HCMA risk. The tacrolimus trough level was not high in HCMA but was significantly high in HCMA in the low post-VR setting (p=0.002). Among LDKTRs, low hemoglobin level is an important contributor to the manifestation of HCMA in the induction period, and increased intrarenal post-glomerular blood flow is a key condition for the development of CNI-induced RTA.