Enzymuria and low molecular weight protein excretion as the differentiating marker of complications in the early post kidney transplantation period

Abstract

Renal function in the early post-transplantation period depends largely on factors affecting the kidney prior to implantation. Function of the graft may be also disturbed by the most common complications of the early post-operative period such as acute graft rejection (AGR), acute tubular necrosis (ATN) and may be modified by nephrotoxic action of cyclosporine A (CsA). Evaluation of excretion of enzymes and low molecular weight proteins (LMWP) may help in the differentiation of these complications. Aim Comparison of the urinary excretion of markers of tubular injury in patients with AGR, ATN, or patients with stable graft function (SGF) was made and differences between groups and correlations between markers and cold ischemia time (CIT), warm ischemia time (WIT) and blood trough level of cyclosporine A (CsA0) were determined. Material and methods In 60 cadaveric renal allograft recipients in the early post-transplantation period urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG) and B isoenzyme (NAG-B), alanylaminopeptidase (AAP), gamma-glutamyltransferase (GGT), alpha and pi isoenzymes of glutathione S-transferase (alpha-GST, pi-GST), retinol binding protein (RBP) and beta2- microglobulin (beta2M), were analyzed. Results NAG and NAB-B activities were higher in ATN (P<0.05, P<0.01) and in AGR (P<0.005, P<0.02) than in SGF. Excretion of pi-GST was higher in AGR than in SGF (P<0.0002) or ATN (P<0.007). CIT and WIT in patients with ATN were higher (P<0.05) than in SGF group. In ATN patients, correlations of CIT with RBP (P<0.05) and pi-GST (P<0.05), and WIT with RBP (P<0.05), and pi-GST (P<0.001) were found. Conclusions High urinary NAG and NAG B excretion characterizes ATN and AGR patients. Evaluating urinary excretion of pi-GST may be helpful in differentiating AGR from ATN. However, taking into account ischemia time is necessary in interpreting the pi-GST value in early post transplant period.

Enzyme Biomarkers of Renal Tubular Injury in Arterial Surgery Patients

“…2,7,16,17 The main finding of this study is that factors, which chronically alter renal function, such as diabetes and hypertension, probably influence the detection of these enzymes after surgery, and therefore influence their use as markers of tubular dysfunction.…”

Significance of Alanine Aminopeptidase N (APN) in Bile in the Diagnosis of Acute Cellular Rejection After Liver Transplantation

“…In kidney transplantation, urinary enzymes and low molecular weight proteins were reported to be useful for the diagnosis of acute rejection after the early posttransplantation phase [4][5][6]. The analogy of ''urine'' excreted from the transplanted kidney is ''bile'' from the allograft liver.…”

“…In kidney transplantation, urinary enzymes or lowmolecular weight proteins are considered useful markers of ACR during the early post-transplantation period [4,5]. Other biomarkers of ACR after renal transplantation are being investigated at present using proteomic analysis of urine [6,7].…”

Urinary glutathione S-transferases in the pathogenesis and diagnostic evaluation of acute kidney injury following cardiac surgery: a critical review

“…Urinary α-GST has been used in clinical practice to assess the degree of damage from warm ischaemic time and consequent chance of nonfunction of machine-preserved nonheart-beating donor kidneys [6]. Acute graft rejection after renal transplantation greatly increases the excretion of π enzyme in the urine without affecting the levels of the α protein, correlating with the distal tubular injury seen in the renal biopsies [14]. In contrast, nephrotoxic drug injury caused by calcineurin inhibitors may principally affect proximal tubules and can result in elevations of α-GST with no change in π-GST expression [5].…”