Summary of proximal tubule transporters and expected effects of drugs modulating their activity. For details see text.
| Target . | Expected effect . | Evidence . |
|---|---|---|
| SGLT2 | (i) Kidney protection, reduced progression of kidney disease | (i), (ii), (iv) animal studies and multiple RCTs |
| (ii) Reduced progression of cardiovascular disease | (iii) retrospective analysis of pats data, RCT ongoing | |
| (iii) Protection from kidney stones | ||
| (iv) Reduction in systemic inflammation | ||
| NHE3 | (i) Diuretic action in pats with decompensated heart failure | (i) RCTs |
| (ii) Reduce AKI | (ii) Animal studies | |
| (iii) Reduce salt-sensitive hypertension | (iii) Animal studies | |
| URAT1 | (i) Reduce serum urate levels in gout | (i) Animal studies and clinical trials |
| (ii) Prevent CKD progression | (ii) Animal studies, not supported by clinical trials | |
| NaPi-IIa | Reduce phosphate overload in CKD, reduce cardiovascular morbidity | Mouse and rat studies |
| OCT1/2, OATs | Reduce accumulation of nephrotoxic drugs/metabolites | Animal studies |
| B0AT1 | (i) Lowering of phenylalanine levels in phenylketonuria | Mouse studies, entering phase 1 and 2 clinical trials |
| (ii) Reduce severity in AKI/Balkan nephropathy |
| Target . | Expected effect . | Evidence . |
|---|---|---|
| SGLT2 | (i) Kidney protection, reduced progression of kidney disease | (i), (ii), (iv) animal studies and multiple RCTs |
| (ii) Reduced progression of cardiovascular disease | (iii) retrospective analysis of pats data, RCT ongoing | |
| (iii) Protection from kidney stones | ||
| (iv) Reduction in systemic inflammation | ||
| NHE3 | (i) Diuretic action in pats with decompensated heart failure | (i) RCTs |
| (ii) Reduce AKI | (ii) Animal studies | |
| (iii) Reduce salt-sensitive hypertension | (iii) Animal studies | |
| URAT1 | (i) Reduce serum urate levels in gout | (i) Animal studies and clinical trials |
| (ii) Prevent CKD progression | (ii) Animal studies, not supported by clinical trials | |
| NaPi-IIa | Reduce phosphate overload in CKD, reduce cardiovascular morbidity | Mouse and rat studies |
| OCT1/2, OATs | Reduce accumulation of nephrotoxic drugs/metabolites | Animal studies |
| B0AT1 | (i) Lowering of phenylalanine levels in phenylketonuria | Mouse studies, entering phase 1 and 2 clinical trials |
| (ii) Reduce severity in AKI/Balkan nephropathy |
RCT, randomized controlled trial; AKI, acute kidney injury.
Summary of proximal tubule transporters and expected effects of drugs modulating their activity. For details see text.
| Target . | Expected effect . | Evidence . |
|---|---|---|
| SGLT2 | (i) Kidney protection, reduced progression of kidney disease | (i), (ii), (iv) animal studies and multiple RCTs |
| (ii) Reduced progression of cardiovascular disease | (iii) retrospective analysis of pats data, RCT ongoing | |
| (iii) Protection from kidney stones | ||
| (iv) Reduction in systemic inflammation | ||
| NHE3 | (i) Diuretic action in pats with decompensated heart failure | (i) RCTs |
| (ii) Reduce AKI | (ii) Animal studies | |
| (iii) Reduce salt-sensitive hypertension | (iii) Animal studies | |
| URAT1 | (i) Reduce serum urate levels in gout | (i) Animal studies and clinical trials |
| (ii) Prevent CKD progression | (ii) Animal studies, not supported by clinical trials | |
| NaPi-IIa | Reduce phosphate overload in CKD, reduce cardiovascular morbidity | Mouse and rat studies |
| OCT1/2, OATs | Reduce accumulation of nephrotoxic drugs/metabolites | Animal studies |
| B0AT1 | (i) Lowering of phenylalanine levels in phenylketonuria | Mouse studies, entering phase 1 and 2 clinical trials |
| (ii) Reduce severity in AKI/Balkan nephropathy |
| Target . | Expected effect . | Evidence . |
|---|---|---|
| SGLT2 | (i) Kidney protection, reduced progression of kidney disease | (i), (ii), (iv) animal studies and multiple RCTs |
| (ii) Reduced progression of cardiovascular disease | (iii) retrospective analysis of pats data, RCT ongoing | |
| (iii) Protection from kidney stones | ||
| (iv) Reduction in systemic inflammation | ||
| NHE3 | (i) Diuretic action in pats with decompensated heart failure | (i) RCTs |
| (ii) Reduce AKI | (ii) Animal studies | |
| (iii) Reduce salt-sensitive hypertension | (iii) Animal studies | |
| URAT1 | (i) Reduce serum urate levels in gout | (i) Animal studies and clinical trials |
| (ii) Prevent CKD progression | (ii) Animal studies, not supported by clinical trials | |
| NaPi-IIa | Reduce phosphate overload in CKD, reduce cardiovascular morbidity | Mouse and rat studies |
| OCT1/2, OATs | Reduce accumulation of nephrotoxic drugs/metabolites | Animal studies |
| B0AT1 | (i) Lowering of phenylalanine levels in phenylketonuria | Mouse studies, entering phase 1 and 2 clinical trials |
| (ii) Reduce severity in AKI/Balkan nephropathy |
RCT, randomized controlled trial; AKI, acute kidney injury.
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