Stable renal function after islet transplantation: importance of patient selection and aggressive clinical management

Abstract

Background: Proteinuria development and decrease in glomerular filtration rate (GFR) have been observed after successful islet transplantation. The aim of this study was to determine clinical, laboratory, and immunosuppressant-related factors associated with kidney dysfunction in islet transplant recipients.

Methods: A retrospective cohort study was conducted in 35 subjects submitted to pancreatic islet transplantation for treatment of unstable type 1 diabetes mellitus. Demographic, anthropometrical, and laboratory data, as well as immunosuppressive and antihypertensive therapy were recorded. Kidney function was assessed by albuminuria and estimated GFR (eGFR), calculated by modification of diet in renal disease formula.

Results: Age was the only independent risk factor for low eGFR (<60 mL/min/1.73 m2) (odds ratio [OR]=1.78 [1.22-2.61]). Low-density lipoprotein cholesterol (OR=2.90 [1.37-6.12]) and previous microalbuminuria (OR=6.42 [1.42-29.11]) were risk factors for transient macroalbuminuria. Interestingly, tacrolimus was a protective factor for macroalbuminuria (OR=0.12 [0.06-0.26]). Six of 30 (20%) normoalbuminuric subjects at baseline progressed to microalbuminuria. No subject developed sustained macroalbuminuria. Surprisingly, overall eGFR remained stable during follow-up (before transplant: 74.0+/-2.0; during immunosuppressive therapy: 75.4+/-2.8; and after withdrawal: 76.3+/-5.3 mL/min/1.73 m2; P>0.05). Even subjects with low eGFR and microalbuminuria at baseline (n=10) maintained stable values posttransplantation (61.13+/-3.25 mL/min/1.73 m2 vs. 63.32+/-4.36 mL/min/1.73 m2, P=0.500).

Conclusions: Kidney function remained stable after islet transplantation alone. The unchanged kidney function found in this sample may be attributed to healthier kidney status at baseline and possibly to prompt treatment of modifiable risk factors. Aggressive treatment of risk factors for nephropathy, such as blood pressure, low-density lipoprotein cholesterol, and careful tacrolimus levels monitorization, should be part of islet transplant recipient care.

Figure 1

(A) Pre- and post-transplant eGFR (line equations pre-: y=76.512± −0.034x vs. post-transplant: y=76.109± −0.015x, P=0.400 for slopes comparisons), (B) pre- and post-transplant albuminuria [0–24 months: 11.7 (0–632.5), 24–48 months: 25.6 (0–1112.3), >48 months: 13.4 (0–387.4) mg/24 h, P=0.065], (C) post-transplant eGFR and (D) albuminuria in patients with baseline normoalbuminuria and CKD stage 1 or 2 (white circles) vs. baseline microalbuminuria and/or CKD stage 3 (black circles). P<0.05 for differences between groups (white circles vs. black circles) and P>0.05 for differences between pre- and post-transplant values for both groups. eGFR = estimated glomerular filtration rate, CKD = chronic kidney disease