Table 3:
Summary of the effects of mTOR inhibitors in renal diseases
| Setting | Effect of mTOR inhibitor | |
|---|---|---|
| Pre-clinical models | Clinical studies | |
| Healthy kidney | No histologic abnormalities160 Deterioration in GFR in spontaneously hypertensive rat163 |
No effect on renal function (serum creatinine levels) after 8 weeks of treatment283 |
| Diabetes mellitus | Attenuates renal hypertrophy mitigates albuminuria175–177 | No direct studies; use of sirolimus post-islet transplant associated with proteinuria284 |
| Systemic lupus erythematosus | Preservation of renal mass and renal function, improved glomerular histological findings, decreased anti-double stranded DNA antibodies |
One human study, improvements in renal function and proteinuria in 3 of 5 patients184 |
| Adriamycin nephropathy | Preservation of renal function, amelioration of glomerulosclerosis and tubular dilatation180, 189 | No human disease equivalent |
| Anti-GBM disease, Goodpasture’s disease and crescentic GN | Concurrent with disease induction: improved proteinuria and renal histology After disease induction: worsening proteinuria and inflammatory infiltrates201 |
Case report of SRL reducing ANCA titre285, another case report suggesting limited utility owing to adverse events286 |
| Thrombotic microangiopathy | Impaired recovery190 | No human studies; SRL has been associated with TMA in renal allografts |
| Chronic glomerulonephritis | In Thy 1.1 nephritis, low dose prevents compensatory glomerular hypertrophy, renal inflammatory cell infiltration192 | 6 out of 11 patients with chronic glomerulonephritis and pre-existing proteinuria were treated with rapamycin developed acute renal failure287 |
| Chronic kidney disease | Induces proteinuria, interstitial fibrosis and glomerulosclerosis in a rat remnant kidney model251 | - No formal human studies |
| Membranous nephropathy | Mitigated proteinuria, and reduced immunoglobulin deposits in rats with Heymann nephritis199 | No formal human studies |
| IgA nephropathy | Protected kidney function, reduced IgA deposition and prevented proteinuria increase196 | Improved GFR, decreased endocapillary proliferation204 |
| FSGS | No studies | Evidence of complete and partial remission205, cases of nephrotoxicity reported287 |
| Minimal change nephropathy | No studies | Complete remission when combined with tacrolimus208 |
| Polycystic kidney disease | Decreased kidney enlargement and cyst volume; improved renal function 213 | Unimpressive results, high adverse effect profile288 |
| Acute kidney injury | Delayed recovery289 | Delayed recovery136, 137 |
| Angiomyolipoma | Decreased tumour burden, cyst size and increased survival in a mouse model of TSC290 | Long-term treatment effective in reducing tumour volume256, 263 Neoadjuvant use of sirolimus facilitates nephron-sparing resection261 |
| Renal cell carcinoma | Temsirolimus and the TORKinib Ku0063794 both inhibit tumor growth in a xenograft model of RCC291 | Several inhibitors tested without great success in advanced disease292 including temsirolimus,293 everolimus,294 deforolimus295 and CCI-779296 |
Abbreviations: ANCA, anti-neutrophil cytoplasmic antibody; FSGS, focal segmental glomerulosclerosis; GBM, glomerular basement membrane; GN, glomerulonephritis; NA, not applicable; TSC, tuberous sclerosis complex.